trust formulary

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

RLBUHT Trust Formulary

October 2011

Contents (Click on heading to go to that section)

Preface Dispensing for Discharge Prescribing in Palliative Care Prescribing for the Elderly Therapeutic Concentration Monitoring Dosage Adjustments for Medicines in Renal Impairment Haematology and Biochemistry Reference Ranges Gastro-intestinal System Cardiovascular System Respiratory System Central Nervous System Infections Endocrine System Obstretics, Gynaecology and Urinary Tract Disorders Treatment of Malignant Disease and Immunosuppression Medicines Affecting Nutrition and Blood Musculoskeletal and Joint Diseases Medicines Acting on the Eye Medicines Acting on the Ear Nose and Throat Medicines Acting on the Skin Immunological Products and Vaccines Medicines Used in Anaesthesia


http://staffintranet/Library/document_library/departments_and_services/diagnostics_and_therapeutics/Pharmacy/Antimicrobial%20Therapy%202010-11.pdf

PREFACE This formulary has been designed to guide the prescribing of staff on all wards and departments in this Trust. It also contains prescribing guidelines for specific therapeutic areas, e.g. management of alcohol withdrawal, triple therapy for ulcer healing, anticoagulation. The format is in the style of the British National Formulary (BNF), the most recent edition of which should be used in conjunction with this document for more detailed prescribing information. Technical issues/problems with the intranet version should be addressed to the Pharmacy Directorate Information Analyst (ext. 4559). Comments and suggestions on content may be made to the Chairman of the Medicines Management Group (MMG) or the Assistant Director of Pharmacy – Clinical services.

Restricted or Special Medicines Certain medicines in the formulary are not available for general use. These are indicated in the text by the symbol (s), with details of the restrictions that apply. These restrictions only apply to the initiation of a prescription.

Non - formulary Medicines Wherever possible, only formulary items should be prescribed. If there is a specific need to start an individual patient on a non - formulary preparation then this can be achieved at the request of a Consultant by the completion of a compassionate use request form. This is then discussed with the Chair of the MMG for a decision. Please note however, as non - formulary preparations are not generally stocked in the pharmacy there may be a delay of 24 hours (up to four days at weekends and bank holidays) whilst supplies are purchased.

Patients Admitted On Non - Formulary Medicines If patients are admitted on non - formulary medicines, it is Trust policy that they are maintained on their medication in cases where changing to a formulary preparation would be detrimental to that patient's care. Where these factors are not important e.g. choice of antacid, haemorrhoid preparation, etc. then the doctor should prescribe only formulary items. Guidance on Prescribing - For guidance on prescribing please refer to the trust prescribing of medicines policy

Use of Unlicensed Medicines – refer to Trust policy on the supply and use of unlicensed medicines


New Medicine Policy

Introduction New medicines bring valuable advantages for patients and the health service. The use of new medicines however has to be carefully managed for several reasons: New medicines may bring benefits but may also bring new and perhaps unrecognised hazards; they have implications for the finances of both the Trust and primary care. There are concerns about the education of medical and non-medical staff in their use and sometimes with pharmacy management and stock keeping of new medicines. That a medicine is new is never a sufficient reason alone to introduce it to the hospital – there must be reasonable evidence that it is superior in some way to that which is already prescribed (safety, efficacy, convenience or cost) or that it treats a previously untreatable condition.

Process A case for a new medicine must be made by a consultant to the Medicines Management Group (MMG) addressing the following points:

Clinical advantages of the new therapy Likely therapies to be replaced Likely levels of use Net cost to the trust Impact on other directorates Any service implications (monitoring, change in patterns of care, new patients

treated etc., in the RLBUHT and also elsewhere in the health service including other hospitals or primary care)

The application is to be made on appropriate forms available from Pharmacy. It is the responsibility of the consultant to present the case in person to the MMG. Documents, which present an inadequate case, will be returned for further submission. Submissions must be counter signed by the relevant clinical director and also have the directorate accountants support if there are financial implications.

Decision In making a recommendation, the MMG will use its judgement as to whether this represents a good use of NHS resources. Any formal economic evaluations available will be used to inform this process.


Principles for decision

1) The MMG will not approve new medicines where there are reasonable licensed alternatives already available within the Trust.

2) No unlicensed medicines should be approved except in very exceptional circumstances, where no licensed alternative is available.

3) A case made by several consultants within a discipline should be considered more favourably than one made by a single consultant.

4) The views of all relevant consultants in a particular specialty about a new medicines application may be sought.

5) Any medicine to be considered by NICE within the next 4–6 months will not be considered, pending the publication of NICE guidance (this would not prohibit use in the meantime on a named patient basis by a particular consultant).

6) All medicines with a major implication for primary care prescribing or use outside the hospital (including shared care arrangements) will be discussed with PCT/ primary care representatives.

7) All decisions that affect primary care will need to be ratified by the North Mersey Area medicines Management Committee

Mechanism of working

1) Some responses can be dealt with by chairman’s action alone (where change is therapeutically sound in chairman’s opinion and has no minor service/resource implications).

2) More complex issues or where the chairman feels unable to support the application or where there are major service/resource implications will be referred to the MMG at its next meeting. The requesting consultant is required to attend the meeting in person to present and discuss the case.

3) The MMG will inform the consultant responsible for submitting the application of the decision in writing.

Time Scale

In circumstances 1, a positive response is usually possible within two weeks. In 2, a response may be possible within two months. If there are major financial implications the response will depend on the

negotiations with Commissioners

Urgent New Medicine Requests To be made personally to the Chairman of the MMG via a completed

compassionate use form with justifications, or in his absence to the Clinical Director of Pharmacy who will liaise as necessary with the Medical Director.

Appeal A consultant has a right of appeal against any declined request. The first recourse of appeal will be to the MMG. If rejected on appeal to MMG, then

appeal may be made to the Medical Director in consultation with the Chairman of the MMG


"Dispensing For Discharge" Scheme and use of Patients Own Medicines (POMs) Definition

‘Dispensing For Discharge’ is medication supplied from the Hospital

Pharmacy labelled with full dosage instructions so that these supplies can be used during in-patient stay and for discharge.

The ‘POMs scheme’ refers to use of patient's own medicines (dispensed in the community) during their inpatient stay (and on discharge), if assessed as appropriate, in accordance with set protocols.

Scope The scheme currently operates on all wards at RLUH and several wards at Broadgreen Hospital.

Aims/Advantages

Minimise delay in the supply of medicines at discharge because medication is available in sufficient quantity and is labelled with dosing instructions on the ward.

Meet government guidelines on best practice as outlined in "A Spoonful of Sugar" (Audit Commission 2001) and NSFs.

Re - deploy pharmacy staff time in a patient focused manner and speed up the discharge process.

Reduce medication administration errors because the nurse is only selecting from the patients’ own medicines which are stored at the bedside.

Minimise occurrences of ‘medicines not available’ because the time interval between prescribing and administration of medication may be reduced.

Medication charts remain on the ward because Pharmacy staff are ward based.

Reduce waste because the patient's own medicines ("POMs") are used rather than destroyed. Hospital supplied medication for in-patient use is also used for discharge.

Medication administration rounds are quicker and timelier because nursing staff are not limited by a single trolley and only have to search one patient's medicine locker for the appropriate medication.

Reduce patients’ confusion about medication and improve concordance with therapy by explaining the need for changes in brand / medicine / dose / frequency.

Pre – admission

Patients should be encouraged to bring in all their medication from home for assessment and possible continued use in hospital.



Entry into the Scheme

Patients will only be entered into the scheme after a medication chart (with full medication administration details) has been completed by a doctor.

Pharmacy Element of "POMs" Scheme (Ward level) Each ward on which the scheme operates will be assigned a Clinical Ward Pharmacist (WP) and a Medicines Management Technician (MMT).

The ward will be visited by the WP and MMT throughout the day during the week. A limited service is provided to all wards over the weekend whereby a pharmacist will visit during pharmacy opening hours to collect requisitions and discharge prescriptions. No medication charts should be sent to the Pharmacy dispensary. A WP and MMT provide a limited service to the Acute Medical Admissions Unit during pharmacy opening hours on Saturday and Sunday mornings.

The WP will clinically check prescriptions for appropriateness of therapy as per Trust / clinical guidelines.

The WP will be available as a Medicines Information source at ward level, and may be contactable via a pager.

The MMT will be involved in various medication issues such as assessing POMs and ordering medication from Pharmacy under the guidance of the WP. MMT’s carry a pager, they are contactable during the day to deal with stock queries and checking of discharge prescriptions (TTO’s) to speed up the discharge process.

Use of Patients’ Own Medicines (POMs) and “Dispensing for Discharge Scheme”

Medicines Supply Process

Pat i e n t ad m i tte d to

wa rd

Me d i ca t i o n c ha rt

c o mp l e te d b y M e di c a l

Sta ff

Cl e rki n g - i n sta f f to

as c e rtai n i f a n y PO M s

bro u g h t i n to h o sp i tal

Me d i ca t i o n s up p l y arra n g e d by W P/M MT o n ne x t vi si t

I f m e d ic a t io n is req u i re d b e fo re thi s vi si t , n u rsi n g s ta ff sh o u ld on ly ord e r th o s e m e d i ci n es wh ic h a re n o t av a i la b le a s wa rd sto c k

Me d i ca t i o n to b e sto re d in th e b e d s id e me d i ci n e s c a bi n e t

(e x c ep t i n ha l e rs, to p i c al p re pa ra t i o ns , me d i ci n e s re q u ir in g refr ig e ra ti o n a nd CD’ s )

Yes

No

M MT a ss e s se s PO M’ s

NO T s ui ta b le fo r c on t i n ue d u se –p ati e n t to c on s e nt fo r re mo v a l o f PO Ms

SUITA BL E fo r c on t i n ue d u se –ve rb a l c on s e nt to u se i nd i ca te d a s ‘ O wn ’b y W P/M MT

No s u pp l y re q u ire d

W P /M M T en d o rs es Ph a rm ac y se c t io n o f ch a rt wi th : a t i c k i n the OW N s e ct i o n , n u mb e r o f d ay s s u pp l y, L /N fo r l ab e l l ed wi th i n stru c tio n s , o r n o t, d a te of a s se s s me n t a n d re -su p p ly d a te

Su p p l ie s re q u ire d fro m Ph a rm ac y

M EETS “ Di sp e n si n g

fo r Di s ch a rg e ”

c rite ri a

EXC L UDED fro m

“ Di sp e n si n g fo r

Di s ch a rg e ”

2 8 d ay su p p ly i ss u e d

W P /M M T en d o rs es “P ha rm a cy ” s ec t i on o f ch a rt wi th n um b e r o f d a ys s up p l y a n d d a te of s u p pl y “ L” (fo r L a b el l e d ) a n d re -su p p l y d a te

Ap p ro p ri ate q ua n t i ty s up p l i ed

W P /M M T en d o rs es Ph a rm ac y se c t io n o f ch a rt wi th Qty su p p l ie d ; da te o f s u pp l y a n d re -su p p ly d a te

‘ N’ e nd o rs e me n t to i n d ic a te m e d ic i ne s “n o t l a be l l e d fo r d i sc h ar ge ”

Ke y:

W P W a rd Ph arm ac i st

M MT Me di ci n es Ma na g em en t Tec hn i ci an


Discharge Procedure

A discharge prescription must be completed, even if no medication is required to be dispensed as a copy is sent to the patient's GP by the ward clerk.

Process of Completion of TTO

An electronic TTO is written by a registered prescriber. An unauthorised copy of the TTO must be printed off and a member of the ward

pharmacy team contacted. Endorsement on the TTO of what requires dispensing and when there is already

“quantity sufficient” (QS) on the ward or at the patient's home (QSH). The TTO must be authorised by a pharmacist following a clinical check of the

prescription (which includes checking for transcription errors from medicine chart onto TTO prescription).

Completion of the dispensing procedure, either on ward using pre-packs and ward labellers or in the dispensary (if any medication requires dispensing).

Ward staff must print 3 copies of the completed discharge summary, one for the patient, one for the medical notes and one to be posted to the GP.

It is the responsibility of the discharge nurse (must be a Trust accredited registered nurse) to check all medication against the discharge summary before handing over to patient or carer.


Use of Patients’ Own Medicines (POMs) and “Dispensing for Discharge”

Discharge Medicines Supply Process (TTO)

Dis charge pre scription

created and an u n-authori sed

co py p rinted off. Bleep W P/MMT

Cl inica l assessmen t and autorisa ti on of prescri ption by phar macist

If disp ensing requ ired medi cines returned to ward : -

Some/all medi cati on

req uired to be disp ensed

Medi cines disp ensed

Trust accre dited

and registered

nurse to p rint au th oriseddi scharge

summary and check before

issue of di scharge medicin es

NO med icat ion requ ired to b e disp ensed

•Endors ed QS/QSH on the TTO by Pharmacy staff to i ndica te suffi cient quan ti ty

Pati ent ha s at least 7 days supp ly?

All medi cines/dosa ges match those on di scharge

pre scription?

Remove di scontinu ed medici nes from pa ti ent l ocker

C ontact ward p harmacist (WP/MMT)

C ontact Pha rma cy Techn ician (W P/MMT)

NO

NO

Patie nt to be given cop y of d ischarg e su mmar y and cop y to be f iled in ca se n ote s.


PRESCRIBING IN PALLIATIVE CARE Contents (Click on heading to go to that section) Pain Control General principles W.H.O Analgesic Ladder Assessment and Management of Pain W.H.O Analgesic Ladder Step 1 – Mild Pain Step 3 – Moderate Pain Step 3 – Severe Pain Opioid Dose Conversion Ratios Nausea and Vomiting in Palliative Care Restlessness and Confusion Breathlessness Syringe Driver Therapy


Pain Control - General Principles

Pain is what the patient says it is and should be treated to the patient's satisfaction.

The perception of pain is affected by factors such as insomnia, depression, anxiety, etc. and these should be addressed alongside the direct treatment of pain.

Accurately diagnose cause of pain as some forms of pain are only partially responsive to opioids.

80% of patients will have more than one site of pain. Unless otherwise indicated, always use the oral route. Use REGULAR analgesia once source of pain is diagnosed. Do NOT

prescribe pain relief “when required” (except for breakthrough pain). Prescribe fast acting analgesia for breakthrough pain in addition to

maintenance therapy. Manage pain according to the W.H.O. analgesic ladder. Set realistic goals by negotiation with the patient. Re-assess frequently. Consider non-medicine treatments. Anticipate unwanted side effects of medication e.g. constipation , nausea and

vomiting

W.H.O. Analgesic Ladder

STEP 1 STEP 2 STEP 3

Strong opioids ** Morphine Diamorphine + adjuvant*

Weak opioids ** Codeine phosphate + adjuvant*

Simple analgesics Paracetamol + adjuvant*

*Adjuvant drugs may include co - analgesics e.g. NSAIDs, tricyclics, gabapentin or other means of pain relief e.g. radiotherapy, intercostal block etc. ** Dose reduction required for patients with renal impairment and the elderly


Assessment and Management of Pain A full history and examination of the patient should be undertaken. Remember that the patient may have more than one type of pain and their pain may not be related the main diagnosis.

Cause of pain Management

Visceral W.H.O. analgesic ladder : see above

Headaches Non specific Paracetamol ‘when required’

Raised ICP Seek senior medical advice immediately

Gastro-intestinal pain Constipation Consider regular laxatives and enemas if indicated

Obstruction Faecal softeners e.g. docusate sodium and/or

antispasmodics Non-opioid analgesics If problem persists contact Palliative Care Team

Colic Hyoscine butylbromide 20mg by s.c. injection

repeated after 30 minutes if necessary. Can be added to a syringe driver for s.c. administration. Check compatibilities)

Muscle spasm Muscle relaxants such as baclofen (5-10mg three times a day), diazepam (2-10mg daily) are useful

Metastatic bone pain NSAID plus morphine. Seek senior advice. Radiotherapy may be appropriate for solitary metastases. (Consider bisphosphonate if widespread metastases and bone pain at multiple sites)

Nerve compression Addition of dexamethasone (8mg daily in divided doses) may reduce the compression on a nerve. Avoid giving dexamethasone after 2pm. Seek senior or pain specialist advice. Consider role of radiotherapy

Nerve pain Burning, itching, stabbing, electric shock type pain. Treat according to W.H.O. ladder. Co-analgesics are important for neuropathic pain as it may respond only partially to opioids, these agents include gabapentin, amitriptyline, pregabalin, carbamazepine and clonazepam

Pleural pain Antibiotic if appropriate. Intercostal block if localised (seek anaesthetic advice) Analgesia (NSAIDS).

Incident Pain Ensure adequate background analgesia. Contact Pain Team


W.H.O. Analgesic Ladder

STEP 1: MILD PAIN Simple analgesics

Non opioid analgesics to be given regularly for mild pain.

Medicine of choice is Paracetamol. Intravenous paracetamol is restricted to Anaesthetists, Palliative Care and

the Pain Team only, for use post–operatively in patients where the oral route is inappropriate, or following the Palliative Care Teams advice. It should be converted to the oral or rectal route as soon as possible.

Move to Step 2 if correctly administered regular non - opioids are ineffective.

STEP 2: MODERATE PAIN Weak opioids

Used in addition to non - opioids for mild to moderate pain Medicines of choice are codeine phosphate and dihydrocodeine.

Co-codamol 8/500 or 30/500 may be more easily tolerated by patients on multiple medications. Even weak opioids cause side effects such as constipation and nausea. Patients may develop tolerance to nausea and vomiting but not to constipation, so prescribe prophylactic laxatives to patients receiving regular doses of opioids.

Move to Step 3 if weak opioids become ineffective.

STEP 3: SEVERE PAIN Strong opioids

See below


Choice of medicine Morphine is the strong opioid of choice for oral analgesia. It is contra-indicated in renal failure. If GFR<30ml/min or if creatinine >200, seek specialist palliative care advice.

Choice of route Oral administration is the route of choice when available. Parenteral administration should only be considered if there is reduced consciousness in the last few hours or days of life, vomiting or severe dysphagia. The preferred parenteral route is subcutaneous which is as effective as the intramuscular route and much less painful. Transdermal fentanyl should only be used for stable pain and should be avoided or used with caution in elderly. It is one of the recommended opioids for use in patients with renal impairment, following palliative care advice. It is second line treatment.

Choice of dose and formulation The starting dose of a strong opioid should be dependent upon the patient's previous analgesic requirements, age and general condition. For frail and elderly patients smaller doses may be sufficient. Seek specialist advice for patients in renal failure

Starting doses Previously on a non - opioid analgesic - Start with 2.5 to 5mg morphine sulphate liquid orally as needed. Previously on a weak opioid - Start with 2.5 to 5mg of morphine sulphate liquid or short acting tablets (Sevredol®) every 4 hours and when required.

Titrate the dose to the patient's pain. The aim is to prevent the pain returning

before the next dose. After each dose of opioid monitor response and review. Regular analgesic requirements can be assessed by calculating the total dose

of morphine administered in the previous 24 hours.

Prescriptions for morphine and oxycodone must specify either "immediate" or "sustained release" preparation. Use the brand name for the preparation used. Initiation of oxycontin® and oxynorm® is restricted to Acute Pain Team and Palliative Care Team only.

Once pain is controlled, oral morphine liquid / immediate release tabs can be

converted to a 12 hourly - sustained release preparation using the total daily morphine dose given (click here for approximate equivalent doses).

Morphine liquid should always be prescribed 'when required' after conversion

to a slow release preparation to manage any breakthrough pain and calculate further amendments to the regular dosing schedule. Prescribe one sixth of the daily morphine dose as a `when required' dose. e.g. when a patient is on


12hourly sustained release morphine tablets, 120mg twice daily orally, the correct breakthrough dose of morphine liquid (oramorph® 10mg/5ml) is 1/6 of 240mg (total daily dose is 2x120mg) which equals 40mg prn PO.

Click here for strengths of morphine sulphate preparations available.

Fentanyl is available in a transdermal patch formulation. This can ONLY be

used in patients whose analgesic requirements are stable and where the patient’s condition is stable (not patients who are deteriorating). Seek Palliative Care Team advice if considering using fentanyl patches

If pain remains uncontrolled despite several breakthrough doses of analgesia,

contact specialist team for advice.

There is no maximum dose of strong opioid if the patient is in pain, and not opioid toxic. It is possible for a patient with opioid resistant pain to become toxic if their pain is unresponsive to opioids. The effect of each opioid dose should be assessed. If the patient appears toxic but still in pain or is getting no relief from their ‘when required’ opioid, contact the Palliative Care team.

Always prescribe regular combination (softener plus stimulant) laxatives for

patients on regular opioids (strong or weak).


Summary Guidelines for Use of Strong Opioids Always prescribe regular combination laxatives and ‘when required’ anti-emetics

Oral route of choice

Previous analgesia Regular doses of weak opioid Regular doses of non-opioids 2.5-5mg morphine sulphate 2.5-5mg Morphine sulphate liquid liquid every 4 hours every 4 hours

Is it effective?

YES NO Continue with same dose. Increase dose by 25-50 % Monitor efficacy Convert to oral slow release preparations. Calculate total opioid requirement and divide by 2. e.g. required 4x 10mg doses of morphine liquid in previous 24 hours = 40mg oral morphine in 24 hours = 20mg of morphine SR tablets (MST) every 12 hours. Maintain ‘when required’ dose of morphine liquid for breakthrough pain (one sixth of total daily morphine dose) If regular SR morphine tablets are not controlling pain increase the doses according to the total amount of ‘when required’ doses used, but do not increase by more than 50% of previous 24 hour dose (as advised above). Increase by 30-50%. Remember to increase breakthrough doses as the SR doses go up. If oral route not available use subcutaneous injections or 24 hour infusion instead. NB immediate release morphine tablets also available (Sevredol®) If there is evidence of toxicity please reduce the opiate dose by 30-50% and reduce the breakthrough doses correspondingly.


Preparations

Paracetamol tablets/suppositories

By mouth or rectum, 0.5 - 1g every 4 to 6 hours when required. Max. 4g daily

Diclofenac By mouth or rectum, 50mg – 150mg daily in divided doses Sustained release tablet 75mg twice daily

Codeine phosphate By mouth, 30mg tablets, 25mg/5ml syrup 30 - 60mg every 4 hours when required. Max 240mg daily.

Co-codamol This is a combination of paracetamol and codeine phosphate Do not co-prescribe with paracetamol. Available in tablet and dispersible formulations, 8/500 and 30/500 strengths. Maximum 8 tablets in 24 hours

Dihydrocodeine By mouth, 30mg tablets, 10mg/5ml syrup 30-60mg every 4 to 6 hours when required. Max. 240mg daily

CD Morphine sulphate

By mouth Please prescribe all oral opioids by the dose in mg. Prescribing by volume (e.g. ml) is not acceptable as they come in different preparations and concentrations and may lead to the wrong dose being given.

Short acting preparations; Morphine sulphate 10mg/5ml available as oral solution Morphine sulphate is also available as a concentrated

oral solution 20mg/1ml. For use in patients requiring very high doses of morphine

Morphine sulphate tablets 10mg, 20mg, 50mg (Sevredol®)

Long acting preparations (twice daily)

Morphine sulphate s/r tablets 5mg, 10mg, 30mg, 60mg, 100mg, 200mg

Morphine sulphate s/r sachets , 20mg, 30mg, 60mg, 100mg, 200mg.

Morphgesic is the brand kept at RLBUHT There are other preparations that patients may be

admitted on including MST, Zomorph, Morcap. Please contact, pharmacy or palliative care team if unsure of preparation.

Extra long acting preparations (once daily)

Morphine sulphate m/r capsules (MXL®) Palliative Care Team only, unless patient admitted on this brand when any doctor can prescribe.

Parenteral preparations:

Morphine sulphate injection 10mg, 15mg, 20mg, 30mg.


CD Diamorphine injection

Available as 5mg, 10mg, 30mg, 100mg, 500mg vials

CD Oxycodone By mouth Please prescribe all oral opioids by the dose in mg. Short acting preparations – immediate release

Oxynorm oral solution 5mg/5ml Oxynorm concentrated oral solution 10mg/ 1ml

Long acting preparations (twice daily)

Oxycontin 5mg, 10mg, 20mg, 40mg, 80mg tablets Parenteral preparations:

Oxycodone injection 10mg/ml 2ml ampoules

CD Fentanyl

Palliative Care / Pain Team only Patches: mcg per hour patches: 12, 25, 50, 75, 100 Sublingual tablets (Abstral®): 100mcg, 200mcg, 300mcg, 400mcg, 600mcg, 800mcg Nasal Spray (PecFent®): 100mcg, 400mcg

CD Hydromorphone Palliative Care Team only Oral preparations only in both immediate and modified release forms.

CD Alfentanil Palliative Care Team only Subcutaneous use only, very potent and short acting. Safer in renal failure than other opioids.


Opioid Dose Conversion Ratios General approach This is a summary of selected opioid dose conversion ratios. These can be used to calculate equivalent doses of opioids when switching from a weak opioid to morphine, or from one strong opioid to another. Caution is always necessary. Conversion ratios can never be more than an approximate guide because of:

Wide inter-individual variation in opioid pharmacokinetics Other variables such as nutritional status and concurrent medication Data derived from single dose rather than chronic dose studies.

Thus, careful monitoring during conversion is necessary to avoid both under-dosing and excessive dosing. This is particularly the case if:

switching at high doses there has been a recent rapid escalation of the first opioid switching to methadone.

When switching at high doses (e.g. morphine or equivalent doses of ≥1g/24h), it is generally good practice to prescribe a lower than calculated dose (e.g. 1/3–1/2 lower), and rely on p.r.n. doses to make up any deficit while re-titrating to a satisfactory dose of the new opioid. In a comparably cautious way, when there has been a recent rapid dose escalation of the first opioid, use the pre-escalation dose to calculate the initial dose of the second opioid

The Tables below relate mainly to switching to or from morphine. If switching from an opioid other than morphine to another opioid, it will be necessary to convert the dose of the first opioid to morphine equivalents, and then use that quantity to determine the dose of the second opioid. With any switch:

round the calculated dose up or down to the nearest convenient dose of the preparation concerned, e.g. tablet, TD patch, ampoule

decide on an appropriate p.r.n. dose.

The conversion ratios are taken from the 3rd edition of the Palliative Care Formulary.


Approximate dose conversion ratios: PO to PO

Conversion Ratio Calculation Example

Codeine to morphine 10:1 Divide 24h codeine dose by 10

Codeine 240mg/24h PO →morphine 24mg/24h PO

Dihydrocodeine to morphine 10:1 Divide 24h dihydrocodeine dose by 10

Dihydrocodeine 240mg/24h PO →morphine 24mg/24h PO

Hydrocodone to morphine 1.5:1 Divide 24h hydrocodone dose by 1.5 (decrease dose by 1/3)

Hydrocodone 60mg 24h PO→morphine 40mg/24h PO

Tramadol to morphine 10:1 Divide 24h tramadol dose by 10

Tramadol 400mg/24h PO →morphine 40mg/24h PO

Morphine to hydromorphone

5:1a

7.5:1b

Divide 24h morphine dose by 5 Divide 24h morphine dose by 7.5

Morphine 60mg/24h PO →hydromorphone 12mg/24h PO Morphine 60mg/24h PO →hydromorphone 8mg/24h PO

Morphine to methadone Variable Contact palliative care for advice

Morphine to oxycodone

1.5:1 2:1b

Divide 24h morphine dose by 1.5 (decrease dose by 1/3) Divide 24h morphine dose by 2

Morphine 30mg/24h PO →oxycodone 20mg/24h PO Morphine 30mg/24h PO →oxycodone 15mg/24h PO

a. for converse, some use 1:4, e.g. hydromorphone 8mg/24h PO→morphine 32mg/24h PO b. italicized entries=manufacturers’ recommendations.

See below for dose conversion ratios; PO to SC/IV and SC/IV to SC/IV


Approximate dose conversion ratios; PO to SC/IV


Hydromorphone to hydromorphone

2:1 Divide 24h hydromorphone dose by 2

Hydromorphone 32mg/24h PO → hydromorphone 16mg/24h SC/IV

Methadone to methadone 2:1a Divide 24h methadone dose by 2

Methadone 30mg/24h PO → methadone 15mg/24h SC/IV

Morphine to alfentanil 30–40:1 Divide 24h morphine dose by 30–40

Morphine 40mg/24h PO → alfentanil 1mg/24h SC/IV

Morphine to diamorphine 3:1 Divide 24h morphine dose by 3Morphine 30mg/24h PO → diamorphine 10mg/24h SC/IV

Morphine to hydromorphone 10–15:1 Divide 24h morphine dose by 10–15

Morphine 30mg/24h PO → hydromorphone 2mg/24h SC/IV


Morphine to morphine 2:1 Divide 24h morphine dose by 2Morphine 30mg/24h PO → morphine 15mg/24h SC/IV

Morphine to oxycodone 2:1 Divide 24h morphine dose by 2Morphine 60mg/24h PO → oxycodone 30mg/24h SC/IV

Oxycodone to oxycodone 1.5:1 2:1b

Divide 24h oxycodone dose by 1.5 (decrease dose by 1/3) Divide 24h oxycodone dose by 2

Oxycodone 30mg/24h PO → oxycodone 20mg/24h SC/IV Oxycodone 30mg/24h PO → oxycodone 15mg/24h SC/IV

a. because the mean oral bio-availability is 80% (range 40–100%), some centres use 1:1, e.g. methadone 30mg/24h PO→ methadone 30mg/24h SC/IV b. italicized entries=manufacturers’ recommendations.

See below for dose conversion ratios; SC/IV to SC/IV


Approximate dose conversion ratios; SC/IV to SC/IV


Morphine to alfentanil 15–20:1Divide 24h morphine dose by 15–20

Morphine 40mg/24h SC/IV → alfentanil 2mg/24h SC/IV

Morphine to buprenorphine 30–40:1Divide 24h morphine dose in mg by 30–40

Morphine 40mg/24h SC/IV → buprenorphine 1mg /24h SC/IV

Morphine to hydromorphone 5:1 Divide 24h morphine dose by 5

Morphine 30mg/24h SC/IV → hydromorphone 6mg/24h SC/IV


Morphine to oxycodone 1:1 Use same dose as 24h morphine dose

Morphine 30mg/24h SC/IV → oxycodone 30mg/24h SC/IV

Side Effects of Opioid Analgesics

Constipation: Prophylactic combination laxatives should be given routinely to all patients receiving regular opioids. Titrate the dose to the degree of constipation.

Nausea, vomiting Occurs in approximately 30% of patients, usually mild and self-limiting. Approximately 1% have persistent N+V secondary to their opioid as it usually resolves within 72hours. Prophylactic anti - emetics should be prescribed 'when required'

Sedation and confusion Usually mild and self limiting lasting 2 - 3 days. If persistent reassess and consider dosage, alternatives and adjuvant drugs. Consider dose reduction or switching opiates

Respiratory depression Tolerance Dependence/addiction

Safe if titrated upwards gradually. If guidelines are followed these side effects are not a problem in palliative care. For further advice contact the palliative care team.


Co – analgesics Metastatic Bone Pain NSAIDs are the analgesic of choice if there is an inflammatory component. All NSAIDs are gastric irritants whichever route they are administered by and are contra-indicated in severe renal impairment. NSAIDs and opioids are often used in combination.

Ibuprofen tablets/syrup 400mg 3 times daily after food increased if necessary. Maximum dose 2.4g daily.

Diclofenac By mouth 25 - 50mg 3 times daily after food or 75mg m/r twice daily or 100mg m/r once daily. By rectum 100mg at night. Maximum daily dose by any route is 150mg.

Celecoxib capsules

By mouth, 100mg - 200 mg twice daily Consult BNF for contra-indications

Neuropathic pain

Amitriptyline tablets Start with 10-25mg, (10mg in the elderly) taken in the early evening to avoid hangover effect. Pain relief may begin in 1 – 7 days. Rate of increase depends on pain level and degree of supervision. If tolerated dose may be increased by about 25mg every three days to 100mg at night. Elderly: rate of increase may need to be slower e.g. 25mg per week. Caution in cardiac disease as increases the risk of tachyarrythmias

Gabapentin capsules Initial dose 300mg at night on day 1 300mg BD on day 2 300mg TDS day 3 Maximum dose is 3600mg in divided doses Side effects may be sedation or drowsiness and myoclonus which can be mistaken for opioid toxicity.

Pregabalin Second line after trying gabapentin/ amitriptyline Initial dose 25mg BD Gradual titration to a maximum dose of 300mg BD.

Others including; clonazepam, sodium valproate, carbamazepine

Palliative Care Team initiation only


Constipation This is a common problem and is often a cause of great discomfort and distress. Prevention is the best strategy and all patients receiving opioids should receive combination laxatives. All patients will require a regular softener in addition to a stimulant laxative. In cases of established constipation potentially reversible causes should be excluded, such as bowel obstruction, hypercalcaemia, anticholinergic medications, dehydration, etc.

Stimulant laxatives Co-Danthramer – restricted indication. Use restrictes to terminally ill patients of all ages only. This is a combination of danthron which is a stimulant laxative and a poloxamer which is a stool softener. Danthron is an irritant to the skin and should not be used in incontinent patients as it may cause blistering and burns. Warn patients about change in urine colour (dark red). 4 step method for titration of codanthramer: Step 1: Codanthramer 25/200 suspension 10ml on or Codanthramer 25/200 capsules 2 caps on

Step 2: Codanthramer suspension 10ml bd or Codanthramer capsules 2 caps bd Step 3: Codanthramer (75/1000) strong suspension 5ml bd or Codanthramer strong (37.5/500) capsules 2 caps bd Step 4: Codanthramer strong suspension 10ml bd or Codanthramer strong capsules 4 caps bd

Codanthramer 25/200 caps and suspension 1-2 caps (5-10ml) at bedtime initially to be increased to bd as needed

Strong Codanthramer caps 37.5/500 1-2 caps at bedtime to be increased to bd as needed

Strong codanthramer suspension 75/1000 in 5ml

5ml –10ml at bedtime to be increased to bd as needed

Senna tabs/ syrup 7.5mg 2-4 tablets at bedtime

Docusate sodium caps 100mg / oral solution 50mg/5ml

Up to 500mg daily in divided doses


Docusate is a stool softener that has weak stimulant properties. In doses above 400mg/24h it acts as a stimulant and a softener. Avoid elixir as it tastes unpleasant. Osmotic/ Bulk forming Laxatives Lactulose Movicol Magnesium hydroxide These work by retaining and drawing fluids into the bowel lumen and increasing stool bulk. They are not recommended in Palliative patients as they are burdensome as the volume of liquid taken with osmotic laxative does not contribute to hydration and is kept within the gut, but usually limits what the patient can then tolerate orally and it may contribute to dehydration. Extension of the gut wall causes increased peristalsis but they are not stimulants and therefore not considered combination laxatives. Lactulose increases wind.

Opioid induced constipation For opioid induced constipation subcutaneous methylnaltrexone (Relistor®) a peripheral μ-opioid antagonist may be considered and is licensed for the induction of prompt bowel movements when response to usual laxative therapy has been insufficient. It comes in 12 mg/0.6 mL single-use vials for subcutaneous use every other day, although longer intervals will be permitted, as per clinical need. It works, on average, within 2 hours. The recommended dose is 8 mg for patients weighing between 38-62 kg or 12 mg for patients weighing 62-114 kg. Patients whose weight falls outside of these ranges should be dosed at 0.15 mg/kg. It is not licenced for use in renal or hepatic failure. Methylnaltrexone should only be prescribed following Palliative Care Team advice.


Nausea and Vomiting in Palliative Care It is very important that the cause is identified as treatment varies. Constipation, intestinal obstruction, medicine induced and hypercalcaemia are common causes of nausea and should be rectified by appropriate treatments. If nausea persists for more than 48 hours gastric stasis may occur and oral medicines will not be absorbed. Use subcutaneous route. Note – the subcutaneous route is an off licence route of administration. Anti - emetics acting at the chemoreceptor trigger zone are useful during the first few days of opioid therapy. The patient will become tolerant to the nauseous effect of opioids after a few days. Where a single agent has failed to control nausea, a combination of an agent acting at the chemoreceptor trigger zone and one acting at the vomiting centre will often be effective. (e.g. cyclizine and Haloperidol)

Anti - emetics acting at the Chemoreceptor Trigger Zone (CTZ)

Haloperidol By mouth or s/c injection 1.5mg at night upto BD

Metoclopramide By mouth, s.c* or i.m. injection 10mg 3 times daily By s.c. infusion via syringe driver* 30 mg over 24 hours in water for injection. *Subcutaneous route of administration is off licence and higher doses may be recommended by the Palliative Care Team.

Levomepromazine Broad spectrum antiemetic with weaker effects on CTZ than haloperidol and metoclopramide. 6.25mg – 25mg by mouth, s.c. injection or infusion over 24 hours

Metoclopramide is a gastrointestinal prokinetic and may cause colic or perforation if used in complete bowel obstruction.

Anti - emetics acting at the Vomiting Centre

Cyclizine Tablets / injection

By mouth, s.c. injection 50mg 3 times daily or subcutaneous infusion of 150mg over 24 hours

Levomepromazine Broad spectrum antiemetic. 6.25mg – 25mg by mouth, s.c. injection or infusion over 24 hours


Anti - emetics acting on the Gastrointestinal tract Prokinetics

Metoclopramide By mouth, s.c* or i.m. injection 10mg 3 times daily By s.c. infusion via syringe driver* 30 mg over 24 hours in water for injection. *Subcutaneous route of administration is off licence and higher doses may be recommended by the Palliative Care Team.

Domperidone By mouth 10-20mg 3-4 times daily Per rectum (30mg suppositories) 30-60mg bd

Gut chemoreceptors

Ondansetron By mouth, s.c. or i.v. injection 4-8mg 3 times daily By s.c. infusion via syringe driver 8-32mg over 24 hours

Granisetron Oncologist only


Excessive Respiratory Secretion Palliative Care Team use only

First Line Hyoscine hydrobromide

By s.c. injection, 400 - 600 micrograms every 4 – 8 hours By s.c. infusion, 1200 - 2400micrograms over 24 hours

May cause sedation / agitation May cause confusion at higher doses

Second line Glycopyrronium

By s.c. injection , 200 - 400microgram every 4-6 hours By s.c. infusion, 1200 - 2400 micrograms over 24 hours

Restlessness and Confusion Medicine choice depends on symptoms described, use midazolam or lorazepam if agitated, haloperidol may be more effective if patient is hallucinating.

Haloperidol tablets/injections

May cause sedation By mouth, 1.5 – 3mg od or prn. (usual maximum 10mg/24hours) By s.c. infusion*, 5mg/ml and 20mg/2ml 3-5mg over 24 hours.

Lorazepam tablets Sublingually, 0.5 – 1mg as required, (maximum 4mg/24 hours)

Midazolam injection CD By s.c. injection 2.5-5mg as required By s.c. infusion* Start with 5-10mg over 24 hours. Titrate up to 30mg over 24 hours as needed. If symptoms still uncontrolled contact the Palliative Care Team for further advice.

* subcutaneous route of administration is off licence.


Breathlessness Medicine choice depends on symptoms described, use midazolam or lorazepam if agitated, haloperidol may be more effective if patient is hallucinating.

Morphine sulphate By mouth / s.c. injection 2.5mg – 5mg every 4 hours.

Lorazepam tablets Sublingually 0.5mg – 1mg as required, (maximum 4mg/24hours) Midazolam 2.5-5mg sc when anxiety is severe

If breathlessness is still a problem refer to the Palliative Care Team.

Syringe Driver Therapy Subcutaneous syringe driver therapy is not a panacea for symptom control. There is no evidence that in chronic cancer pain the parenteral route is more effective. Indications include:

Dying phase if appropriate Persistent nausea and vomiting Severe dysphagia Too weak for oral route Poor absorption

If more than one medicine is to be administered in the syringe driver, specialist advice should be obtained as certain medicine combinations may cause precipitation. (Click here). General guidelines

Change syringe every 24 hours Check infusion regularly, at least every 4 hours, for local skin reactions and

the syringe for precipitation/crystals For advice on medicine combinations contact pharmacy or palliative care team

Calculation of diamorphine Requirements

If patient already taking morphine or other strong opioid: Conversion from oral morphine to subcutaneous diamorphine is 3:1 Calculate the 24 hour dose of morphine and divide this total dose by three. E.g. 90mg of MST twice daily = 180mg morphine sulphate / 24hours = 60mg diamorphine in the pump s.c. over 24hours.

Prescriber must state on the medication chart that the dose is administered over 24 hours


If patient has pain and is not taking morphine or other strong opioid use either:

Diamorphine 2.5 - 5mg s.c. injection PRN every 4 hours OR Diamorphine 10mg by s.c. infusion via a syringe driver over 24 hours

To calculate an appropriate four hourly PRN diamorphine dose for

breakthrough pain: Divide the 24 hour dose of diamorphine in the syringe driver by six e.g. 60mg diamorphine in the syringe driver, prescribe PRN 10mg s.c. every four hours

To calculate the subsequent doses of diamorphine over 24 hours: Add the dose of diamorphine in the syringe driver to the diamorphine given PRN in the previous 24 hours. The maximum recommended dose increase is 50% of the current 24 hour opioid dose. E.g. 30mg in syringe driver over 24 hours and an additional 4 x 5mg prn s.c. doses required in the last 24 hours. The new dose for the syringe driver would work out as 30mg plus 20mg from the prns, as this is more than a 50% dose increase in the syringe driver the maximum safe increase should be to 45mg over 24 hours.

Then calculate a new PRN dose (one sixth of new dose), to ensure that pain requirements are met after increasing the syringe driver dose. In the example above it would be 7.5mg s.c. prn. (one sixth of 45mg)


SYRINGE DRIVER COMPATIBILITIES Always use Water for Injection as diluent Subcutaneous administration of medicines all listed below is off licence

Medicine Compatibility with Diamorphine

Comments

Haloperidol Yes

Metoclopramide Yes

Cyclizine Caution To avoid precipitation keep both Concentrations below 20mg/ml. Use water for

injections as diluent.

Levomepromazine (methotrimeprazine)

Caution Powerful sedative Caution with doses greater than 100mg

Glycopyrronium Yes

Midazolam Yes

Hyoscine hydrobromide Yes

Hyoscine butylbromide Yes Do not use with cyclizine - causes precipitation

Octreotide Yes

Dexamethasone Avoid May be administered as bolus subcutaneous dose, or use a separate syringe driver

If precipitation/ crystallization is seen in the syringe stop the pump, seek pharmacy or palliative care advice, then replace the syringe and line with maximum dilution.


Prescribing For Older People Prescribing for older people can often prove more challenging than for the general adult population. Adverse drug reactions are more common due to multiple pathology and associated polytherapy. Older patients may have difficulty complying with complex regimens involving many medicines, so mistakes are more likely. The side effects of treatment may present atypically and are often incorrectly attributed to the disease being treated e.g. "giddiness" caused by postural hypotension treated as vertigo. There are also age - related changes in the absorption, distribution, metabolism and excretion of medicines, which should be taken into account. End - organ sensitivity to medicines may change e.g. exaggerated central nervous system responses. Practical Guidelines to aid prescribing

1) Make sure that the symptom you are treating is not itself due to current medication. When an older patient is ill, especially if the symptoms are non - specific (e.g. incontinence, confusion), the cause may be a medicine they are taking

2) Remember that non - neurological medicines may have adverse effects on the central nervous system e.g. digoxin which may produce a chronic confusional state.

3) Assume that all medication may produce adverse effects. Weigh the risks against the benefits if prescribing new medication. The prescribing of Non-Steroidal Anti inflammatory drugs especially carries a high risk.

4) Prescribe low doses when indicated. The British National Formulary often gives advice, but if you are uncertain, consult your ward pharmacist or Medicines Information (ext 2096).

5) Keep the number of medicines prescribed to an absolute minimum.

6) Explain the reason for each medicine to the patient, how to take it and when to finish the course. Seek the advice of the pharmacist where necessary for help in ensuring compliance when the patient is discharged from hospital.

7) Be aware of any special precautions or patient monitoring which may be necessary. Plasma level monitoring is mandatory for aminoglycosides e.g. gentamicin, and recommended for other medications such as phenytoin, theophylline, lithium and digoxin

8) Keep all medication under review. Do not repeat prescriptions unless there is

a good reason for continuing therapy.


Compliance Issues Defective hearing, poor eye sight, impaired memory and confusion all contribute to difficulties in understanding and being able to take medication as prescribed. It is important to ascertain who will be administering medication when the patient is discharged from hospital. The first stage in ensuring compliance rests with giving adequate verbal explanation and instructions to the patient and/or their carers. Please discuss any problems identified with medication with the ward pharmacist who is able to provide medication reminder cards or other compliance aids e.g. Haleraids, etc. Medication may be able to be provided in a dosette box/blister pack; however this is not suitable for all patients. An assessment of suitability must be made by the ward pharmacist and arrangements made for provision of this service on discharge. Advance notice, preferably at least 24 hours before discharge is needed to be able to complete this procedure and dispense medication.



Therapeutic Concentration Monitoring Measurement of medicine concentration may be of value in the assessment of compliance, therapeutic control, or confirmation of clinical toxicity. The following table gives guidance on appropriate sampling times and accepted therapeutic ranges for those medicines in which monitoring is advisable because of erratic or unpredictable dose response relationships or narrow therapeutic ranges. The time to steady state indicates the appropriate interval required before blood sampling after the initiation of therapy or dose change. Sampling before this time may produce misleading results. Please note sampling time relative to last dose on blood form. If in doubt, contact your ward pharmacist or Medicines Information (ext. 2096). Advice may also be sought from Microbiology for antibiotic concentration monitoring or from Clinical Biochemistry for other medicines. Note: The medicine interactions listed in the table below are common examples of interactions where plasma drug concentrations are affected. It is not a comprehensive list. Other medicines may interact without affecting plasma concentrations. Refer to the BNF, your ward pharmacist or Medicines Information (ext. 2096) for further information.

MEDICINE PHARMACOKINETIC PARAMETERS

TIME TO STEADY STATE

IDEAL SAMPLING

TIME

ACCEPTED THERAPEUTIC

RANGE

COMMENTS

Aminophylline see Theophylline

Carbamazepine T50 = 12 – 17 hours F (tablet) = 70-79% F (liquid) = 96% Vd = 0.8 to 2L/kg

2 - 4 weeks after starting therapy or 2 - 6 days after dose change.

Trough level. Take immediately before next oral dose.

4 – 10mg/L Metabolism is self induced initially (increase dose over 2 - 4 weeks). Carbamazepine has an active metabolite. Levels ‘d by: Erythromycin, Clarithromycin, Cimetidine.

Ciclosporin CyAMS – measures parent ciclosporin only. CyAMS total – parent medicine and major metabolites

T50 = 19 hours (10-27 hours). F (tablet) = 10-89% Vd = 3.9 to 4.5L/kg

3-5 days Trough level. Take immediately before next dose

Renal Transplant: 150 - 275g/L CyAMS (post-transplant) 100 - 200g/L CyAMS (stable graft conditions) Bone Marrow Transplant: 200 - 300g/L CyAMS Auto-immune disease: 100 - 150g/L CyAMS

For further information see the Laboratory Handbook. In dual therapy for renal transplant levels may be lower. Levels ‘d by: Allopurinol, Erythromycin, Clarithromycin, Ciprofloxacin, hormones, Cimetidine, Fluconazole Levels ‘d by: Enzyme inducing antiepileptics, Rifampicin, St. Johns Wort. Toxic concentration CyAMS > 350g/L. Toxicity is sometimes manifested by raising serum creatinine.



TIME TO STEADY

IDEAL ACCEPTED COMMENTS

STATESAMPLING THERAPEUTIC

TIME RANGE

Digoxin T50 = 36 to 48 hours F (tablet) = 70% F (liquid) = 80% Vd = 4-7L/kg (IBW)

5 - 7 days

At least 6 - 8 hrs after last dose (oral or iv) or immediately pre dose

1 - 2 µg/L Dose reduction may be necessary in elderly or renally impaired. Levels ‘d by: Amiodarone, Calcium Channel Blockers, Quinine and Quinidine.

Lithium T50 = 14-24 hours (up to 36 hours in elderly. Also increased in patients on long term therapy, up to 48 hours). F = 100% Vd = 0.7-1.4L/kg

3 - 7 days

Trough level. Take immediately before next oral dose (doses usually 12 - 24hrly)

0.4 - 1 mmol/L Levels ‘d by: ACE inhibitors, NSAIDs, diuretics, dehydration and renal impairment. Antipsychotics and SSRIs may neurological toxicities due to lithium.

Phenobarbital T50 = 36 hours - 5 days F = 80-100% Vd = 0.5-1L/kg

10 - 25 days

Trough level. Take immediately before next oral dose

10 – 30 mg/L Has a long half life, up to 5 days.



TIME TO STEADY



TIME RANGE

Phenytoin T50 = 7-42 hours F = 70-100% Vd = 0.65L/kg

7 - 35 days

Immediately before next oral dose. (2 – 4 hrs after IV dose)

8 – 15 mg/L The rate of phenytoin metabolism reaches maximum at therapeutic concentrations. Half life with dose (i.e. a small in the maintenance dose can lead to a disproportionate in plasma concentration). Levels‘d by Carbamazepine. Levels may be or by Sodium valproate. Levels ‘d by: Cimetidine, Omeprazole, Metronidazole, Fluconazole.

Sodium valproate (valproic acid)

T50 = 8-20 hours F = 90-100% Vd = 0.1-0.5L/kg

2 - 3 days

Trough level. Take immediately before next oral dose

50 – 100mg/L for epilepsy. 50-125 mg/L for acute mania.

Monitoring only useful to check compliance, therapeutic effect may lag behind therapeutic plasma level. Levels ‘d by Cimetidine. Levels ‘d by Carbamazepine.



TIME TO STEADY



TIME RANGE

Tacrolimus T50 = 9-12 hours (increased in liver dysfunction). F = 14-32% Vd = 0.85-1.91L/kg

2 days Trough level. Take Immediately before next oral dose

Renal Transplant: 10 - 20g/L Auto-immune disease: 5 - 15g/L

Levels >20g/L may be associated with nephrotoxicity and glucose intolerance. Levels ‘d by: Erythromycin, Clarithromycin, grapefruit juice, Fluconazole.

Theophylline Aminophylline

T50 = 3-13 hours F = 100% Vd = 0.5L/kg NB – Aminophylline salt factor is 0.8

2 - 3 days

PO -Trough level. Take immediately before next oral dose. IV – take after patient has been on the infusion for at least 2 hours.

10 – 20 mg/L Levels ‘d by: Cimetidine, Ciprofloxacin, Erythromycin, Clarithromycin. Levels ‘d by: Enzyme inducing anticonvulsants, Rifampicin, smoking.



TIME TO STEADY



TIME RANGE

Gentamicin and Tobramycin (s)

T50 = 2-3 hours in normal renal function. T50 is significantly increased in patients with renal dysfunction, or burns. (may be > 70 hours in anuric patients) F = poorly orally absorbed, must be given parenterally. Vd = 0.25L/kg

24 hours Trough: Immediately before next dose Peak: 1 hr after dose administration

Trough: < 1mg/L Peak: 6 - 10mg/L for most infections Peak is 3-5mg/L for subacute endcoarditits NB peaks are not generally monitored for ONCE a day dosing of aminoglycosides.

See Trust Antimicrobial policy. Note: CAUTION IF CO -ADMINISTERED WITH OTHER NEPHROTOXIC MEDICINES. Generally

peak is affected by dose and the trough affected by frequency.

High concentrations of certain penicillins may inactivate aminoglycosides in vivo e.g. Piperacillin, Ticarcillin.

Amikacin (s) T50 = 2-3 hours in normal renal function. T50 is significantly increased in patients with renal dysfunction, or burns. (may be > 70 hours in anuric patients) F = poorly orally absorbed, must be given parenterally. Vd = 0.25L/kg

24 hours Trough: Immediately before next dose Peak: 1 hr after dose administration

Trough: < 10mg/L Peak: 20 - 30mg/L

Levels may be in elderly, dehydrated or renally impaired patients.

High concentrations of certain penicillins may inactivate aminoglycosides in vivo e.g. Piperacillin, Ticarcillin.



TIME TO STEADY



TIME RANGE


Teicoplanin T50 = 90-160 hours F = poorly orally absorbed, must be given parenterally. Vd = 1.13L/kg

Trough: Immediately before next dose Levels should be taken BEFORE giving the dose on the 3rd or 4th day. NB always give the dose, DO NOT WAIT for levels to be reported.

Trough: 10mg/L

and < 60mg/L.

NB for endocarditis, osteomyleitis and septic arthritis the trough should be > 20mg/L.

See Trust Antimicrobial policy Serum concentration monitoring is required in patients who have any of the following: 1. present with severe infections such as septicaemia or deep seated staphylococcal infection (including bone and joint infection) 2. are intravenous drug abusers 3. present with burns 4. present with impaired, deteriorating, or unstable renal function 5. are undergoing renal replacement therapy (CRRT, HD and PD). Levels are not routinely required for patients not fulfilling the above criteria. Contact microbiology for advice if unsure if levels required


TIME TO STEADY



TIME RANGE

Vancomycin T50 = 4-6 hours in normal renal function. T50 is significantly increased in patients with renal dysfunction, (may be > 7 days in anuric patients) F = poorly orally absorbed, must be given parenterally. Vd = 0.2-1.5L/kg

72 hrs for initial therapy. 24 - 48 hrs after dose change.

Trough: Immediately before infusion. Peak: 1 hr after dose administration

Trough: < 10mg/L Peak: 20 - 30mg/L

VANCOMYCIN MUST BE INFUSED SLOWLY. Recommended rate is 10mg/min to prevent adverse reactions such as hypotension, flushing and transient rash. Dilute to maximum concentration of 5mg/ml (10mg/ml in fluid restricted patients but there is an increased risk of infusion-related thrombophlebitis)

Key T50 = Half life. Vd = Volume of distribution F = Bioavailability IBW – ideal body weight



DOSAGE ADJUSTMENTS FOR MEDICINES IN RENAL IMPAIRMENT

Dosage reductions are traditionally based on the degree of renal impairment classified by three bandings of creatinine clearance. However eGFR is more usually reported and is used in these tables, which are based on the current SPCs (available from www.medicines.org.uk) and the current Renal Drug Handbook, copies of which can be found on renal wards. Neither estimated creatinine clearance nor eGFR are accurate if renal function is unstable, as the serum creatinine used to estimate them may not reflect what is happening within the kidney. For patients not of typical weight for their age, eGFR will diverge from creatinine clearance unless corrected for surface area. Further guidance is available in the BNF. In these patients,

GFR(Adjusted) = eGFR x (Surface area) 1.73 For some drugs, using eGFR will not be accurate enough; these are noted in the tables. Creatinine clearance should be estimated using the method of Cockcroft and Gault, and the relevant SPC should be consulted. The band for CKD Stage 5 usually covers haemodialysis and peritoneal dialysis, but not continuous filtration techniques used in ITU. Increasingly, SPCs, the BNF, and the Renal Drug Handbook diverge slightly in their recommendations, and clinical judgement will be required, In particular, consideration should always be given to: whether renal function is likely to improve or worsen the clinical condition of the patient, especially in severe

infection/immunocompromised patients whether a loading dose is appropriate, especially for antibiotics whether the medicine might itself worsen renal function (e.g. nephrotoxic

antibiotics, NSAIDs, etc) whether the medicine might worsen a problem associated with renal impairment

(e.g. hyperkalaemia, gastrointestinal bleeding). that patients with renal failure are more sensitive to the central nervous system

(CNS) side effects of medicines such as antidepressants, sedatives, antipsychotics, antihistamines and opioid analgesics

that the absence of a medicine from the list does not imply that standard doses can be used.

Further information can be obtained from the Renal Drug Handbook,

www.medicines.org.uk, Medicines Information (2096), and doctors/pharmacists experienced in nephrology.

http://www.medicines.org.uk/


TYPICAL “NORMAL”

DOSE

CKD 3 (eGFR 30-60mL/min)

MODERATE (eGFR 15-30mL/min)

SEVERE (eGFR <15mL/min) (including ESRD)

COMMENTS

ACE inhibitors Start with low dose & adjust according to response. Monitor renal function and plasma potassium closely.

Aciclovir - oral herpes simplex

herpes zoster

Aciclovir –

intravenous (depends on indication)

2-400mg x 5 x

day 800mg x 5 x day

5-10mg/kg TDS

Normal

Normal

5 – 10mg/kg BD (TDS >50mL/min)

Normal

800mg TDS

(Normal >25mL/min)

5 - 10mg/kg OD (BD >25mL/min)

2-400mg BD

(if <10mL/min)

800mg BD (if <10mL/min)

2.5 – 5 mg/kg OD (5-10mg/kg >10mL/min)

For other indications or in dialysis, consult The

Renal Drug Handbook

Allopurinol 100-900mg OD (usually 300mg)

200 – 300 mg OD 100 - 200mg OD 100 mg OD or Alternate Days

In renal impairment, start at 100mg OD & increase if plasma and/or urinary

urate response is unsatisfactory. Less than

100mg daily may be required. Monitor full

blood count. Contraindicated with

azathioprine.

Benzylpenicillin

600mg-2.4g QDS (can go higher)

Normal Some reduction required according to clinical circumstances

600mg-1.2g QDS Nephrotoxic in high doses. High doses can cause cerebral irritation, convulsions, coma. Maximum dose in severe renal failure is 4.8g per day These doses higher than SPC.


TYPICAL CKD 3 MODERATE SEVERE COMMENTS “NORMAL”

DOSE (eGFR 30-60mL/min)

(eGFR 15-30mL/min) (eGFR <15mL/min) (including ESRD)

Cefalexin 250mg QDS-500mg TDS

Normal Normal 250-500mg BD-TDS

Cefotaxime 1-2g TDS (can go higher)

Normal Normal Half dose but not frequency below

5mL/min

Cefradine (oral) 250-500mg QDS

Normal Normal 250mg QDS should suffice

Ceftazidime 1g TDS (can go higher)

1g BD (Normal > 50mL/min)

1g OD 500mg OD (1g OD has been

used)

High doses can lead to neurological complications including encephalopathy, convulsions & coma. On dialysis-see Renal Drug Handbook.

Ceftriaxone 1-4g OD Normal

Normal

Maximum 2g OD

Cefuroxime (IV) 750mg – 1.5g TDS-QDS

(can go higher)

750mg – 1.5g TDS 750mg – 1.5g BD (Normal > 20mL/min)

750mg – 1.5g OD (BD>10mL/min)

Ciclosporin No adjustment needed Nephrotoxic. Monitoring mandatory.

Ciprofloxacin 250-750mg BD (oral)

100-400mg BD (IV)

250mg-500mg BD 50-100% of normal dose BD 50% of normal dose BD

Dialysis patients: See Renal Drug Guide





Clarithromycin 250mg-500mg BD (oral)

500mg BD (IV)

Normal 250-500mg BD (SPC says 250mg BD)

250mg BD

Co-amoxiclav (IV)

Co-amoxiclav (oral)

1.2g TDS

375-625mg TDS

Normal

Normal

1.2 g BD (SPC says 600mg BD)

375mg-625mg BD

IV = 600 – 1.2g BD

375mg BD

Renal Handbook allows higher oral doses

Co-trimoxazole (PCP)

120mg/kg/day in 2-4 doses

Normal

30mg/kg BD from day 4 onwards 30mg/kg BD IV needs to be well diluted- see Renal Drug

Handbook

Dalteparin 2500-5000u (Prophylaxis) 200iu/kg/OD

(VTE treatment)

Normal Prophylaxis: use normal dose. Treatment below 20-30mL/min: can accumulate and cause fatal haemorrhage: monitor antifactor Xa levels for duration of treatment (RLUH does Tuesdays and Fridays, take 6 hrs after dose given). May be appropriate to use reduced dose but evidence weak: consult Haematology. Enoxaparin (Clexane) has a licensed dose.

Digoxin (maintenance)

62.5-250microgram

OD

125-250 microgram daily

125-250 microgram daily (Levels required)

62.5 microgram daily or alternate days

In haemodialysis, give after session, especially if

alternate day regimes used

Enoxaparin (ACS) 1mg/kg BD 1mg/kg BD 1mg/kg OD 1mg/kg OD See notes for dalteparin, above

Ertapenem 1g OD 1g OD 0.5-1g OD (Unlicensed)

0.5g OD (or 1g 3 x week)

(Unlicensed)





Erythromycin 250mg-500mg QDS

Normal Normal

50-75% of normal Max 1.5g daily

(<10mL/min)

Flucloxacillin 250mg-2g QDS Normal Normal

Usual Max 4g Nephrotoxic in high doses

Fluconazole 50-400mg OD Normal Normal

50% dose Haemodialysis patients - can

dose at normal dose 3 x week after HD

SPC suggests half dose after first day whenever

CrCl < 50mL/min

Gabapentin 300mg OD, then BD, then TDS

Start lower than normal, increase according to response See “Severe” for <15mL/min

<15mL/min; Initially 100mg OD, or

300mg alternate days, and titrate

carefully

Further information on SPC at

www.medicines.org.uk

Ganciclovir - intravenous

(Treatment of CMV)

5mg/kg/BD

Considerable reductions needed after first dose. Consult Renal Drug Guide, or SPC at www.medicines.org.uk

Gentamicin IV Varies Considerable reductions needed after first dose. Consult Renal Drug Guide. Daily gentamicin levels required. For high levels - consider reducing frequency rather than dosage. Use other medicines where possible.

Consult Microbiologist / Medicines Information

Imipenem/cilastatin(Primaxin)

(As imipenem)

1g-2g daily in divided doses

500mg TDS-QDS

500mg BD-TDS (>20mL/min)

250mg BD Max 3.5mg/kg BD

Risk of convulsions. More information at:









Meropenem

0.5-1g TDS (can go higher)

500mg-2g BD 500mg-1g BD 500mg-1g OD

Metformin Max 2g/day 25-50% normal Avoid Avoid Causes lactic acidosis in renal impairment

Methotrexate Up to 20-25mg weekly

50-100% normal 50% normal Avoid

Metronidazole 400mg TDS (oral)

500mg TDS (IV)

Normal Normal Normal Slight difference with SPC

Morphine Varies 75% normal Metabolites are more potent than morphine & accumulate in renal impairment with the potential to cause marked respiratory depression & cerebral sensitivity. Extreme caution

is required for self - administration regimens. Consult Renal Drug handbook or Medicines Information for advice.

Pamidronate (Hypercalcaemia

15-90mg Normal Normal Serum Calcium > 4 Give 60 mg

Serum Calcium < 4 Give 30mg

Tazocin 4.5g TDS Normal

4.5g TDS

4.5g BD



TYPICAL “NORMAL”

DOSE

CKD 3 (eGFR 30-60mL/min)

MODERATE (eGFR 15-30mL/min)

SEVERE (eGFR <15mL/min) (including ESRD)

COMMENTS

Teicoplanin 800mg OD Normal (SPC says half dose)

Load for 4 days as normal, then 200mg-400mg every 24-48 hours, or,

as per Med Micro

Load for 4 days as normal, then 200mg-400mg every 48-72

hours, or, as per Med Micro

See Renal Drug

Handbook or SPC at www.medicines.org.uk

Tranexamic acid – oral

intravenous

1-1.5g BD-TDS

0.5-1g TDS

(Depends on weight and indication)

25mg/kg BD

10mg/kg BD

25mg/kg OD-BD

10mg/kg OD-BD

12.5mg/kg OD-BD

5mg/kg OD-BD

See Renal Drug Handbook or SPC at


Valganciclovir (CMV)

900mg BD (treat) or

900mg OD (prevent)

Considerable reductions needed after first dose. Consult Renal Drug Guide, Medicines Information, or SPC at www.medicines.org.uk

EXTREME CARE: CHECK IF DOSE IS FOR

TREATMENT OR PROPHYLAXIS

Vancomycin IV 1g BD Use with Caution Contact Medicines Information on 2096 or see Renal Drug Handbook

ORAL NEEDS NO REDUCTION




Haematology and Biochemistry Reference Ranges

Haematology Normal values Units

Haemoglobin 13.0 - 16.7 (male) 11.8 - 14.8 (female) g / dL

White Cell Count 3.5 - 11.0 109 / L

Haematocrit 39 - 50 (male) 36 - 44 (female) %

Platelets 150 - 400 109 / L

Neutrophils 2.0 - 7.5 109 / L

Coagulation Normal values Units

Prothrombin time * 9.0 - 13.0 secs.

APTT 25.0 - 36.0 (heparin treatment range 1.8 - 3.3 times normal control )

secs.

Fibrinogen 1.5 - 3.5 g / L

D Dimer < 500 nanogram/ml

Biochemistry Normal values Units

Sodium 135 -145 mmol / l

Potassium 3.5 - 5.3 mmol / l

Chloride 99 - 109 mmol / l

Bicarbonate 22 - 33 mmol / l

Urea 2.5 - 7.0 mmol / l

Creatinine 50 - 130 micromol / l

Calcium 2.2 - 2.6 mmol / l

Calcium (adjusted) 2.2 - 2.6 mmol / l

Phosphate 0.7 - 1.4 mmol / l

Magnesium 0.75 - 1.00 mmol / l

Anion gap 6 - 16 mmol / l

Glucose 3.5 - 6 mmol / l

Lactate 0.5 - 2.2 mmol / l

Protein Normal values Units

Total protein 60 - 80 g / L

Albumin 35 - 50 g / L

Bilirubin 2 - 17 micromol / L

ALT 0 - 35 iu / L

Alk. phos. 35 - 125 iu / L

Amylase < 150 iu / L

GGT < 50 (male) < 35 (female) iu / L

CR protein (CRP) < 5 mg / L

Troponin – T ** < 14 nanogram / L

Creatine kinase 33 - 194 (male) 35 - 143 (female) iu / L * Range varies according to condition. ** Sample at least 6 hours post chest pain.


GASTRO - INTESTINAL SYSTEM Contents (Click on heading to go to that section) Dyspepsia and gastro-oesophageal reflux disease

Antacids and dimethicone Antispasmodics and Other Medicines Altering Gut Motility

Antimuscarinics Other Antispasmodics Motility Stimulants

Ulcer - Healing Regimens

Intravenous Acid Suppression Acute Healing

Acute diarrhoea Chronic bowel disorders

Inflammatory Bowel Disease (IBD)

Laxatives Management of Constipation Management of Impacted Faeces Bulk - forming Laxatives Stimulant Laxatives Faecal Softeners Osmotic Laxatives Bowel Cleansing Solutions Guidelines for Pre-op Bowel Preparation of patients

Local preparations for anal and rectal disorders

Soothing haemorrhoidal preparations Compound haemorrhoidal preparations with corticosteroids Preparations for treating Anal Fissures Rectal Sclerosants

Stoma Care Medicines affecting intestinal secretions

Medicines affecting biliary composition and flow Pancreatin

Management of Patients with Chronic Liver Disease


Dyspepsia and gastro-oesophageal reflux disease

Antacids and dimethicone For 'simple indigestion', compound preparations have no clear advantage over simpler preparations and tend to be more expensive. Magnesium containing antacids tend to have a laxative effect. Liquid preparations are more effective than tablets.

Simple Antacids

Magnesium trisilicate mixture

10mL (mixed in water) 3 times daily or as required. Max. 60mL a day before review.

Dimethicone

Infacol liquid (s) Gastroenterologists only. For use as an antifoaming agent during gastroscopy. Unlicensed use

Alginates

Gaviscon Advance liquid (sugar free)

5 – 10ml after meals and at bedtime. (Note: Each 10ml contains 4.6mmol of sodium)

Gaviscon Advance Tablets 1 – 2 tablets after meals and at bedtime (Note: Two tablets contains 4.5mmol of sodium)

Antispasmodics and Other Medicines Altering Gut Motility

Antimuscarinics

Hyoscine butylbromide Acute spasm: By i/v or i/m injection 20mg, repeated after 30mins if necessary. (maximum of 100mg in 24 hours) Note: Hyoscine butylbromide tablets are poorly absorbed therefore are of little use for acute spasm.

Hyoscine butylbromide (s) tablets

Chronic disorders only.



Other Antispasmodics

Alverine citrate capsules

60-120mg TDS

Mebeverine 135mg 3 times daily, preferably 20 minutes before meals.

Peppermint water 10mL when required

Peppermint oil e/c capsules

(s) Gastroenterologists and Surgeons only.

Motility Stimulants Metoclopramide and domperidone are dopamine antagonists that stimulate gastric emptying and small intestinal transit, and enhance the strength of oesophageal sphincter contraction. Domperidone is preferred for patients under 20 years of age since metoclopramide may occasionally induce an acute dystonic reaction. Domperidone is also preferred for long term use where possible since it is less likely to cause dystonic reactions. For disorders such as gastroparesis, erythromycin may be added (unlicensed indication) if standard motility stimulants are unsuccessful. The usual dose is 125mg QDS (increased to 250 mg QDS if necessary).

Ulcer - Healing Regimens

Intravenous Acid Suppression Intravenous H2 antagonists are ineffective for the treatment of an acute bleed. There is some evidence that an intravenous proton pump inhibitor (PPIs) may reduce re - bleeding from known ulcers, (to only be initiated after a review by either a consultant gastroenterologist or gastro SPR). There is no evidence to support the use of STAT doses of IV PPls in acute situations before the patient has had an endoscopy.

Ranitidine injection For prophylaxis only when oral route not available: 50mg diluted to 20mL and given i.v. over at least 2 mins 3 times daily

Omeprazole injection See algorithm on the next page

Pantoprazole injection See algorithm on the next page

Algorithm to Aid Decisions Regarding the Prescribing of IV PPIs


Acute Healing

Helicobacter pylori Positive Ulcers (Eradication Therapy)

Studies have demonstrated that in one week regimens that include a proton pump inhibitor and clarithromycin with either metronidazole or amoxicillin, H. pylori eradication is achieved in 90% or more patients. The combination of amoxicillin and clarithromycin is preferred first line. If amoxicillin cannot be used because of true penicillin allergy, clarithromycin and metronidazole can be used instead. Remind patients to avoid alcohol if taking metronidazole.

Choice of eradication regimen should depend on: Known allergies Known resistance or exposure within last two years to metronidazole / tinidazole - avoid metronidazole containing regimens. If the patient has had a previous course of eradication therapy a C13-urea breath test should be performed before considering a second course of treatment using a different combination of antibiotics. If in doubt consult a gastroenterologist.

Triple Therapy Regimen 1

Omeprazole capsules

20mg twice daily for 1 week

OR

Lansoprazole capsules


PLUS

Amoxicillin capsules

1g twice daily for 1 week

PLUS

Clarithromycin tablets



Or for penicillin allergic patients

Omeprazole capsules


OR



PLUS

Clarithromycin tablets


PLUS

Metronidazole tablets


If clarithromycin cannot be used regimen 2 can be followed.

Regimen 2

Omeprazole capsules


OR



PLUS

Amoxicillin capsules

1g twice daily for 1 week

PLUS

Metronidazole tablets


Helicobacter pylori Negative Ulcers

Duodenal Ulcer Healing

Omeprazole capsules

20mg – 40mg daily for 4 weeks

OR


30mg daily for 4 weeks.


Gastric Ulcer Healing

Omeprazole capsules

20mg – 40mg daily for 8 weeks

OR


30mg daily for 8 weeks.

All patients with gastric ulcers should be re-scoped and biopsied on completion of the course. Subsequent relapses should be referred to a gastroenterologist. H2 antagonists should not be prescribed `when required'. These agents should be reserved for patients who cannot tolerate PPIs, since PPIs are the first line choice for ulcer healing.

Ranitidine tablets/dispersible tablets

300mg at night or 150mg twice daily for 4 – 8 weeks

Maintenance Therapy For complicated ulcer, frequent relapses or co - incidental disease.

Ranitidine tablets 150mg at night.

Omeprazole capsules

20mg daily

NSAID Ulcer Prevention In patients requiring long - term NSAID therapy who are at risk of developing GI bleeding and ulceration lansoprazole or omeprazole may be used to prevent NSAID - associated ulcers. H2 antagonists have not been shown to be effective for this purpose. Combination products of misoprostol and NSAIDs (e.g.“Arthrotec®”) are not available in the Trust. The components should be prescribed separately when required.

Prophylaxis of NSAID - induced Gastric or Duodenal Ulcer

Omeprazole capsules

20mg once daily

OR


15 - 30mg once daily


Treatment of NSAID Related Duodenal / Gastric Ulcer Patients on NSAID treatment who develop a gastric or duodenal ulcer can be treated with a proton pump inhibitor. Upon healing of the ulcer, the proton pump inhibitor dose may be reduced to a maintenance dose.


15 - 30mg once daily for 4 weeks, continued for further 4 weeks if not fully healed.

Omeprazole capsules

20mg once daily for 4 weeks, continued for further 4 weeks if not fully healed


Flow Chart for Management of Patients with Gastro-oesophageal reflux disease (GORD) (Adapted from NICE Guidelines 2004: Dyspepsia –

Management of adults with dyspepsia in primary care)

GORD

Endoscopy result? Oesophagitis Endoscopic negative reflux disease

Omperazole 40mg OD for 1-2 months

Omeprazole 20mg OD for

1 month

Response

No response or relapse

Esomeprazole 40mg OD OR Omperazole

40mg BD (unlicensed dose) for 1

month

No response

No response

Ranitidine 300mg ON or Domperidone 10mg TDS for

1 month

Ranitidine 300mg ON or Domperidone 10mg TDS for

1 month

Low dose treatment

as required

No response

REVIEW

No response

Return to self care


Flow Chart for the Management of Patients With non-ulcer Dyspepsia

(Adapted from NICE guidelines 2004: Dyspepsia – Management of adults with dyspepsia in primary care)


Flow Chart for the Management of Patients with Uninvestigated Dyspepsia (NICE Guidelines 2004: Dyspepsia – Management of adults with

dyspepsia in primary care)

Sucralfate liquid For refractory GORD or patients with banded varices Dose 1g QDS, max. 8g daily. Note: Separate administration of other medicines by 2 hours and enteral feeds by 1 hour from sucralfate


Hypersecretory Syndromes e.g. Zollinger - Ellison syndrome

Omeprazole capsules

initially 60mg once daily up to 120mg daily (above 80mg in 2 divided doses)


Initially 60mg once daily adjusted according to response up to 120mg or more in two divided doses

Acid Aspiration Prophylaxis during General Anaesthesia

In the above guidance lansoprazole oro-dispersible tablets may be substituted for capsules only IF the patient has swallowing problems

Omeprazole capsules

40mg on the preceding evening, then 40mg 2 - 6 hours before surgery

Acute diarrhoea The first line of treatment is the prevention or treatment of fluid and electrolyte depletion with intravenous fluids or oral rehydration sachets e.g. Dioralyte. Anti-diarrhoeal agents should be avoided if an infective cause is suspected, since they may prolong the illness.

Loperamide tablets/syrup

Acute diarrhoea: 4mg initially followed by 2mg after each loose stool for up to 5 days; max. 16mg daily.

Codeine phosphate tablets/syrup

30mg 3 - 4 times daily; max. 240mg daily.

Colestyramine (S) Gastroenterologists only: 12 - 24g (3-6 sachets) daily mixed with water, in single or divided doses, subsequently adjusted as required; max. 36g daily Note: Take all other medicines at least 1 hour before or 4 – 6 hours after dose of Colestyramine.


Chronic Bowel Disorders Inflammatory Bowel Disease (IBD) Treatment of Acute Ulcerative Colitis Acute mild to moderate disease affecting the rectum or recto - sigmoid is treated initially with local application of an aminosalicylate or corticosteroid.

Sulfasalazine Suppositories/enemas

(s) Gastroenterologists only

Mesalazine suppositories/enema/rectal foam

(s) Gastroenterologists and Surgeons only

Hydrocortisone foam enemas (s) Gastroenterologists and Surgeons only

Prednisolone enema/foam /suppositories

(s) Gastroenterologists and Surgeons only

Extensive IBD or disease that does not respond to local therapy requires oral treatment, together with topical therapy. Mild disease affecting the colon may be treated with an aminosalicylate alone but refractory or moderate disease usually requires an oral corticosteroid e.g. prednisolone for 8 weeks. IBD patients are more susceptible to osteoporosis and Calcichew D3 forte 2 OD should be prescribed if these patients are started on steroids. IBD patients over 65 on steroids should additionally also be on a bisphosphonate (see BSG guidelines - http://www.bsg.org.uk/images/stories/clinical/ost_coe_ibd.pdf) If mesalazine is prescribed the brand should be specified due to differences in release profiles/bioavailability. There is little evidence that high doses are more effective in inducing remission therefore standard doses of 2.4g mesalazine (or equivalent) are usually adequate.

Balsalazide capsules (s) Gastroenterologists only

Mesalazine e/c tablets (Asacol/ Mesren)

Mesalazine e/c tablets (s)

(Mezavant)

Ulcerative Colitis and Crohn’s Disease 800mg to 1200mg 3 times daily Gastroenterologists only 2.4g to 4.8 g once daily

Mesalazine s/r tablets (s) (Pentasa)

Gastroenterologists and Surgeons only


http://www.bsg.org.uk/images/stories/clinical/ost_coe_ibd.pdf

Mesalazine e/c tablets (s) (Salofalk)

Gastroenterologists only

Olsalazine capsules (s) Gastroenterologists only reserve for proven left-sided disease only

Sulfasalazine[sulphasalazine ] tablets (s)

Gastroenterologists only

Guidelines for the management of Acute Severe Ulcerative Colitis (UC) Truelove and Witt’s Criteria define severe Ulcerative Colitis as:

Bowels open > 6 times per 24 hours plus any one or more of the following systemic manifestations

Haemoglobin < 10g/dl. Pulse rate > 90 bpm Temperature > 37.5C

The differential diagnosis includes bacterial infection (Clostridium difficile, Campylobacter, Salmonella, Shigella, Escherichia coli 0157), viral infection if immuno-compromised (CMV), amoeba especially if travel history, Crohn’s colitis and ischaemia. Diverticulitis can occasionally mimic symptoms of acute severe UC. Monitor/record DAILY Temperature and pulse – 6 hourly Stool chart Frequency Colour / blood content Estimate of volume (record even if only passed blood or mucus)

Abdominal examination findings: tenderness, bowel sounds Note increasing pulse/temperature/abdominal pain or tenderness may indicate deterioration or frank perforation and requires appropriate urgent investigation and discussion with consultant. Investigations The aim is to confirm the diagnosis, assess severity and extent of disease, and identify / predict complications early. On admission Stool culture + Clostridium difficile x 1 (as a minimum) Sigmoidoscopy and rectal biopsy should be done within 48 hours

admission Bloods

o FBC, UEC, CRP, LFT (albumin), Mg , Glucose, Cholesterol o Blood cultures if temp > 37.5°

Abdominal X-ray: look for stool-free colon (indicates extent involved); severe disease indicated by mucosal oedema (thickened wall),


mucosal islands, dilated small bowel loops, colonic dilatation (diameter > 4.5cm)

Daily (unless consultant requests otherwise) Bloods

FBC, UEC, (particularly note potassium), LFT CRP (a vital prognostic guide)

Abdominal X-ray for severe extensive colitis (any of fever, tachycardia, tenderness, dilatation on initial films) – in absence of these criteria less frequent AXR is OK

Results must be reviewed the same day (especially potassium). Management Approximately 25 – 30% of patients admitted with severe acute UC

will come to colectomy during the same admission. The colorectal surgical team should thus be informed of all patients admitted with acute severe colitis within 24 hours; any patient admitted with acute colitis who is not settling by day 3 should be reviewed by the colorectal team. It is vital that surgeons, stoma therapy team etc are involved to give sufficient time for planning and also allow the patient to come to terms with possible / probable colectomy.

Malnourished patients should be considered for early calorie supplementation, either orally or naso-gastrically. They should be weighed and reviewed by the dietician. Patients with severe disease are often nauseated and anorectic for the first day or two: they are allowed to eat normally.

IV fluids to correct dehydration, with at least 60 mmol potassium per day (eg. Two bags of either one litre glucose 5% or sodium chloride 0.9% one containing 40mmol of KCL and the other 20mmol of KCL)

Patients are highly prone to hypokalaemia due to the diarrhoea and steroid therapy and this requires close attention – particularly if anaesthesia for colectomy is imminent.

Low molecular weight heparin – dalteparin 5,000 units od for all patients who have no contraindications admitted with inflammatory bowel disease regardless of whether mobile or not

Antibiotics, oral metronidazole 400 mg tds, + oral ciprofloxacin 500 mg bd Used in patients with toxic dilatation or febrile with a temperature > 37.8, preferably after stool and blood cultures have been sent or for patients with a first attack of undiagnosed bloody diarrhoea. For UC in the absence of these features antibiotics are not routinely indicated.


Oral 5-aminosalicylates can be withheld whilst on intravenous therapy (there is no evidence that they have a role in acute severe colitis), but restart this on discharge.

Avoid anti-diarrhoeals, opiates etc., and avoid NSAIDs if at all possible. If the patient is experiencing severe pain discuss with consultant.

The steroid regime is IV hydrocortisone 100 mg qds + 5-ASA enemas (e.g. Salofalk® 2g nocte)

Bone protection should be co-prescribed with high dose steroids: low risk - Calcichew D3 Forte 2 daily. high risk (>65yr, known osteoporosis/osteopaenia) - Calcichew D3 Forte

2 daily and alendronate 70mg once a week. 50% of patients with acute severe colitis will make a good response to the

above regime, 25% will require colectomy, and 25% will make a partial response, requiring careful assessment and discussion re increased immunosuppression vs surgery

Definition of failure of steroids: after three days on intravenous

steroids in the context of severe colitis with systemic manifestations as defined above, the presence of

Either Stool frequency > 8 times per 24 hours or Stool frequency > 3 times per 24 hours AND CRP > 45 This gives an 85% likelihood of requiring colectomy. For patients with resistant proctitis these criteria do not generally apply. If patients fail steroids on the above criteria then the choice is between ciclosporin, infliximab and surgery.

Ciclosporin regime (see ciclosporin protocol for full detail)

The patient must give oral informed consent

The following contra-indications must be excluded:

Known hypersensitivity to ciclosporin

Concurrent tacrolimus use

Known hypersensitivity to polyethoxylated castor oils

Uncontrolled hypertension

A serum cholesterol <3mmol/L (increased risk of seizures)

A serum magnesium <0.50mmol/L (increased risk of seizures)

Concurrent rosuvastatin use (convert to alternative statin)


Dose and administration

The recommended dose is 2mg/kg daily administered as a continuous infusion. IV ciclosporin is available as 50mg/ml ampoules. The dose should be diluted to a concentration of 50mg in 50ml of either glucose 5% or sodium chloride 0.9%. The infusion should be administered in a 50ml syringe using a syringe driver. The infusion fluids should not be added to PVC containing bags, to avoid the risk of leaching of plastic into the infusion. The rate of infusion should be calculated as follows: The dose should be prescribed in the IV therapy section of the drug chart

and expressed as “Ciclosporin 50mg in 50ml glucose 5% (or sodium chloride 0.9%), run at xml/hour”

The hourly rate (x) = 2 x weight ------------------

24(hrs) Infusions should be replaced on a continuous basis.

Any dose remaining after 24 hours should be discarded and a new infusion prepared.

Recommendations for Other Medication Corticosteroids: Continue treatment whilst IV ciclosporin is being given. If

remission is achieved, convert to oral prednisolone 40mg OD for 2 weeks, then 30mg OD for 2 weeks, then 20mg OD for 2 weeks, then reduce by 5mg/week to zero thereafter

PCP (Pneumocystis carinii pneumonia) prophylaxis: there is at present no recommendation for the use of PCP prophylaxis . The available evidence suggests that the incidence of PCP is low in patients with UC who receive ciclosporin.

Common interactions: Drugs which may increase ciclosporin levels: macrolides, ciprofloxacin, allopurinol, fluconazole. Drugs which may reduce ciclosporin levels: St John’s Wort, rifampicin, carbamazepine

If the patient is receiving other medicines, pharmacy should be contacted (either via the ward pharmacist or medicines information on ext 2096). Patients should avoid grapefruit and grapefruit juice whilst they are receiving IV ciclosporin since it may increase levels. Monitoring Before administration the following base-line tests should be carried out: Potassium (Range 3.5 – 5.3 mmol/L) – Ciclosporin can cause

hyperkalaemia. Urea and creatinine – Ciclosporin can impair renal function in a dose

related manner. If renal function deteriorates either reduce the dose or cease therapy. If the serum creatinine rises by more than 30% from the baseline value the dose of ciclosporin should be halved


Magnesium (range 0.75 – 1.0 mmol/L) – Ciclosporin enhances the clearance of magnesium; hypomagnesaemia can increase the risk of seizures. Low levels should be corrected before starting therapy

Cholesterol – Hypocholesterolaemia increases the risk of seizures. Liver function tests – Ciclosporin can interfere with hepatic function in a

dose related manner. If liver enzymes or bilirubin become significantly affected (twice the upper limit), reduce dose or stop therapy

Blood pressure (must be <150/90) – Ciclosporin can cause hypertension. During treatment the following monitoring is required: Monitor the patient for the first 30 minutes of the first infusion since the

polyethoxylated castor oil can cause anaphylactic reactions Potassium, magnesium, creatinine, urea, cholesterol and LFTs should be

checked daily BP should be checked four times a day daily Ciclosporin levels should be checked on the third day of treatment. The

recommended trough level is 150-250ng/ml Phone Clinical Chemistry on the day ciclosporin is started to inform that a ciclosporin level is needed on day 3.

Results should be recorded in the monitoring table provided – these will be available from ward 5y or Pharmacy. Duration of Intravenous therapy and Follow Up If during therapy there are clinical signs of worsening of colitis (significant increase in stool frequency or CRP, radiological evidence of toxic colon) ciclosporin should be discontinued and colectomy performed. If the patient is responding to IV ciclosporin it is continued for 7 days before converting to oral therapy 5mg/kg/day in 2 divided doses (aiming for a pre-dose ciclosporin level of 100-200ng/ml) for 3-6 months. Since ciclosporin has not been proven to be beneficial in maintaining remission in UC, all patients should be commenced on either azathioprine or mercaptopurine if they were not taking it previously. Patients should be followed up initially on a weekly basis for the first month and thereafter at 2-4 week intervals until ciclsporin is discontinued and established on a thiopurine. Approximately 50% will respond to ciclosporin, of whom 50% will relapse when ciclosporin is stopped. Even in relapsers the time ‘bought’ can be useful to allow adjustment to the idea of colectomy and its implications. Infliximab Although used, NICE has not approved the routine use of infliximab for rescue therapy in acute severe colitis. However ‘infliximab is recommended as an option for the treatment of acute exacerbations of severely active ulcerative colitis only in patients in whom ciclosporin is contraindicated or clinically inappropriate, based on a careful assessment of the risks and benefits of treatment in the individual patient’ (NICE technology appraisal guidance 163 December 2008) There are ongoing trials to compare ciclosporin versus infliximab in acute UC (CONSTRUCT trial). We are a participating centre in this trial.


Follow up after discharge Patients should be reviewed two weeks after discharge in the out-patient clinic.

Indications for colectomy

Toxic dilatation of the colon: if present on admission, 24-48 hours of intensive medical therapy is warranted provided the patient is sufficiently stable. Failure to respond by 48 hours, or the development of dilatation during medical therapy mandates colectomy.

Perforation Massive bleed All patients who are failing to improve on Day 3 should be discussed with

the colorectal surgeons such that the patient is monitored closely by both medical and surgical teams and if colectomy is required this happens in a planned manner on or soon after day 5. Stoma Therapy, etc will then have had a chance to review the patient, provide explanation and information etc. Few patients who have not made a good response to medical therapy by day 5-7 will subsequently respond, and the risks of surgery escalate with increasing delay

Deterioration at any stage during admission may also necessitate urgent colectomy.


Care Pathway for Management of Acute Severe Colitis

Addressograph Date of admission: _ / _ / _

Referred to Gastro: _ / _

Previous : UC / Crohn’s / indeter / nil

Length of flare: wks

On steroids: Y / N

Mandatory observations / investigations: Record in table

Day 1 Day 3 Day 5 Day 7

Temp

No. of

stools/24hrs

CRP

Albumin

Hb

Plts

Stool culture Sent: 1) _ / _ (date sent)

Result: 1)

CDT Sent: 1) _ / _ (date sent)

Result: 1)

Sigmoidoscopy: _ / _ Macroscopic:

Microscopic:

AXR: 1) _ / _ 2) _ / _ 3) _ / _

Treatment

iv steroids: _ / _

rectal 5-ASAs _ / _

bone protection _ / _

dalteparin _ / _

Ciclosporin: _ / _ level on day 3 ---------------

Management

IBD Nurse Referral: review

Dietician referral: review

Surgical referral: _ / _

Colectomy: _ / _


Management of acute Crohn’s disease Management of these patients requires a consideration of both the location and severity of disease. Oral Mesalazine may be considered for mild ileocolonic disease, though the evidence is very weak Metronidazole 400mg TDS and ciprofloxacin 500mg BD may be used for perianal disease Steroids may be required in severe active disease, although there is a tendency to try to avoid them in ileocolonic disease if possible In addition, patients must stop smoking All patients should be prescribed dalteparin 5000units OD to reduce the risk of thromboembolism following completion of the VTE risk assessment.

Infliximab 100mg Injection (s)

Consultant Gastroenterologists only Infliximab inhibits the activity of tumour necrosis factor. Indicated for Treatment of severe, active Crohn’s disease in patients who have not responded despite full and adequate course of therapy with a corticosteroid and an immunosuppressant or who are intolerant of / have medical contra-indication to such therapy Or Treatment of fistulising, active Crohn’s disease in patients who have not responded despite a full and adequate course of therapy with conventional treatment, (including antibiotics, drainage and immunosuppressive therapy). Dose: 5mg/kg IV administered in 250mL sodium chloride 0.9% over 2 hours.

Adalimumab (s)

Consultant Gastroenterologists only For use in patients with Crohn's disease who fail to respond to infliximab or develop an attenuated response to it.

Before biological therapy is initiated infection must be excluded. A chest x-ray must also be performed to exclude tuberculosis (TB). If there is an abnormal chest x-ray or patient has a history of TB a respiratory consultant should be consulted.


Maintenance of Remission of Acute Ulcerative Colitis

Aminosalicylates e.g. Mesalazine tablets. 1.2 – 2.4g daily in divided doses. Continued use may reduce risk of colon cancer. Avoid lactulose since this will lower stool pH and may prevent the release of mesalazine.

Note: CSM warning in BNF regarding aminosalicylates and the risk of blood dyscrasias/interstitial nephritis.

Azathioprine Unlicensed use If treatment with aminosalicylates fails consider adding Azathioprine: Initially 25- 50 mg OD, increased to max. 2-2.5mg/kg/day

Maintenance of Crohn’s disease

Azathioprine Unlicensed use – consultant gastroenterologists only Initially 25-50 mg OD, increased to max. 2-2.5 mg/kg/day

Methotrexate Unlicensed use – consultant gastroenterologists only 15-25mg WEEKLY by the oral or intramuscular route. Used if patient cannot tolerate azathioprine or azathioprine ineffective

Before patients are initiated on azathioprine they should be tested for TPMT (thiopurine methyl transferase) activity. Low activity warrants starting azathioprine at half dose. All patients receiving azathioprine or methotrexate should have FBC & LFTs monitored every 2 weeks until dose stable, then every 3 months.


Laxatives

Management of Constipation First line treatment includes increasing dietary fibre, mobility and fluid intake, and removing possible medication causes. Identify possible causes of constipation e.g. medicine induced, underlying disease, mechanical obstruction, pregnancy, dehydration, immobility. If first choice treatment is not tolerated or ineffective, the table below indicates alternative management approaches.

First line treatment Second line treatment

Third line treatment

CHRONIC CONSTIPATION

Ispaghula preparations (e.g. Fybogel)

± Senna tablets (i.e. in slow gut transit)

Docusate sodium capsules

MEDICINE - INDUCED CONSTIPATION

Avoid causative agent if possible

Senna tablets

DIET - INDUCED CONSTIPATION

High fibre diet with adequate hydration

Ispaghula preparations (e.g. Fybogel)

Additional Factors to Consider

Elderly Bulking agents may not be suitable for fragile or immobile elderly patients. Short-term use of a stimulant laxative (e.g. senna) with or without a stool softener is more appropriate.

Cardiac failure Defaecation must be free of strain in these patients, hence a stool softener is most appropriate.

Malignancy The cause of constipation should be diagnosed and treated accordingly

Haemorrhoidectomy patients

A bulk forming laxative (Fybogel) and osmotic laxative (Lactulose) are often given together post - operatively to facilitate passing a soft and effective stool.

Psychiatric Constipation arising from depression is resistant to treatment unless the depression is being treated.


Management of Impacted Faeces Faecal incontinence/

discomfortNO Faecal

incontinence/ discomfort

Hard stools:

Lactulose ± senna

Soft stools:

senna

If no effect then:

Daily enema until bowel clear:

sodium citrate enema

phosphate enema

Arachis oil enema (for hard stools)

If no effect then:

Soft stools:

sodium picosulphate

sachet (“Picolax”)

Hard stools:

(manual evacuation)


Bulk - forming Laxatives

Ispaghula husk (Fybogel)

1 to 2 sachets once or twice daily. Should be taken with at least one glass of water and should not be taken immediately before going to bed. Onset of action up to 48 hours. Useful in colostomy/ileostomy patients, but contra - indicated in faecal impaction or existing bowel obstruction.

Stimulant Laxatives

Senna tablets/syrup 2 to 4 tablets or 10 - 20mL at night. Initial dose should be low then gradually increased. Action seen within 12 hours. Usually reserved for short-term use as prolonged use can precipitate the onset of atonic colon and hypokalaemia. May cause abdominal cramps and contra - indicated in bowel obstruction.

Bisacodyl tablets/ suppositories

By mouth, 5 - 10mg at night. Acts in 10 - 12 hours By rectum, 10mg in the morning. Acts within 20 - 60 minutes

Co - danthramer capsules/suspension/strong suspension

1 - 2 capsules or 5 – 10mL at night. Acts within 6 - 12 hours May colour urine and skin red. Note: Only licensed for constipation in terminally ill patients of all ages

Faecal Softeners

Arachis oil enema To soften impacted faeces: One enema daily until bowel clear. Warm the enema to body temperature before use.

Docusate sodium capsules/solution

Up to 500mg daily in divided doses. Acts within 1 - 2 days. Also has a mild stimulant effect.


Osmotic Laxatives

Lactulose 15mL twice daily. Should only be used when other laxatives have failed to produce an effect. Must be taken regularly for 2 - 3 days before an effect is seen therefore not suitable for short term or 'when required' use. Main indication is hepatic encephalopathy when higher doses are used.

Macrogol sachets Used for chronic constipation and faecal impaction.

Sodium citrate enema

One or two daily when required

Phosphate One enema when required. Warm the enema to body temperature before use

Magnesium sulphate enema

(s) Gastroenterologists and Surgeons only Note: Specially manufactured by pharmacy, for use in hepatic encephalopathy only

Bowel Cleansing Solutions The bowel prep of choice for patients undergoing colonoscopies in the Trust is Moviprep. Patients eligible for Moviprep undergoing colonscopies Since Moviprep induces minimal electrolyte shifts it can be used in patients with renal failure. However, dialysis patients must first be reviewed by a renal consultant to determine if these patients need to be admitted into hospital for close fluid balance monitoring. The following contraindications are to be excluded before commencing therapy:

Gastrointestinal obstruction or perforation, ileus, gastric retention, acute intestinal or gastric ulceration or toxic megacolon

Severe acute inflammatory bowel disease Congestive cardiac failure (NYHA grade 3 or 4) Difficulty swallowing Reduced levels of consciousness Hypersensitivity to any of the ingredients Known Glucose- 6 -phosphate dehydrogenase deficiency Known Phenylketonuria

Schedule and administration instructions for Moviprep A course of treatment consists of two litres of Moviprep. A litre of Moviprep consists of one 'Sachet A' and one 'Sachet B' dissolved together in one litre of


water. This reconstituted solution should be drunk over a period of one to two hours. This should be repeated with a second litre of Moviprep. In addition, at least one litre of clear fluid must be consumed in the period taking the bowel prep Time of colonscopy Times to take reconstituted solution Morning list 14:00 and 18:00 the day before the test

Afternoon list 18:00 day before test

08:00 day of the test Evening list 07:00 day of the test

13:00 day of the test Dietary advice 2 Days before the Test Two days before the test the patient may have only low residual food. Foods from the following list are acceptable: boiled or steamed white fish, boiled chicken, potato without skin, egg, cheese, white bread, butter/ margarine, seedless jam, marmite, honey, rich tea biscuits, chocolate, yoghurt, jelly (not red) and ice-cream

Red meat, fruit, vegetables, nuts, pulses or cereals in any form are not to be consumed

1 Day before the Test

Morning Appointment: After a light breakfast (cereal) the day before the test (morning list) patient should eat NO further solid food until after the investigation. Patients with diabetes should replace each mealtime with one Ensure drink.

Clear fluids intake is strongly encouraged (as much as possible) as advised in the relevant sections and can be taken up to 2 hours before the test. Clear fluids include fruit juices (without pulp), fizzy drinks or tea and coffee(without milk). Bovril and clear soup and sugary drinks such as Lucozade are also acceptable.

Afternoon Appointment: After a light lunch – soup without bread- day before the test (morning list) patient should eat NO further solid food until after the investigation. Patients with diabetes should replace each mealtime with one Ensure drink.

Clear fluids intake is strongly encouraged (as much as possible) as advised in the relevant sections and can be taken up to 2 hours before the test. Clear fluids include fruit juices (without pulp), fizzy drinks or tea


and coffee(without milk). Bovril and clear soup and sugary drinks such as lucozade are also acceptable.

Evening Appointment. After a light evening meal the day before the test (morning list) patient should NO further solid food until after the investigation. Patients with diabetes should replace each mealtime with one ensure drink.

Clear fluids intake is strongly encouraged (as much as possible) as advised in the relevant sections and can be taken up to 2 hours before the test. Clear fluids include fruit juices (without pulp), fizzy drinks or tea and coffee(without milk). Bovril and clear soup and sugary drinks such as Lucozade are also acceptable.

Nothing should be consumed from 2 hours before the test

Patient’s regular medicines

Iron and constipating medicines i.e. loperamide, codeine phosphate should be stopped five days before the test. The patient’s other regular oral medication should be continued as normal but taken at least one hour before administration of bowel cleansing agents. On the day of the test patients with diabetes should omit their diabetic medication. If patients are on the contraceptive pill they must be advised to take additional precautions for up to 7 days after taking bowel cleansing agents

The decision whether to withhold oral anticoagulants or clopidogrel is based on the risk of the patient bleeding as a result of the procedure/intervention against the risk of a thromboembolic event as a result of interrupting anticoagulation/clopidogrel therapy. Aspirin and dipyridamole therapy can be continued as normal. Current advice is based on the BSG guidelines, “Guidelines for the management of patients on warfarin or clopidogrel undergoing endoscopic procedures” updated 2008 http://www.bsg.org.uk/pdf_word_docs/anticoagulant_08.pdf


http://www.bsg.org.uk/pdf_word_docs/anticoagulant_08.pdf


Other available bowel cleansing agents

Sodium picosulfate sachet (Picolax)

One sachet dissolved in water and taken before 8am and second sachet the afternoon of the day before the operation/investigation. Maintain high fluid intake, and monitor sodium closely Note: Should not be used for patients with obstructive or nearly obstructive lesions of the colon.

Fleet Phospho Soda Bowel prep only. Dilute one bottle (45ml) in half a glass of water (120ml) and drink this followed by at least one glass (240ml) of water. The second bottle should be taken 12 hours later. Not suitable for use by patients with renal impairment.

Gastric lavage solution (Klean Prep)

Bowel prep only. Reconstitute one sachet in 1 litre of water and drink 250mL every 10 - 15mins until rectal effluent is clear or 4 litre dose consumed. Note: Ensure high fluid intake is maintained to prevent volume depletion. May be alternative for patients with renal failure.

Guidelines for Pre-op Bowel Preparation of Patients

Electrolyte management 1) Check recent potassium. If less than 4.0 mmol/l give two tablets of Sando K (Each tablet contains 12 mmol

of K+). 2) Patients with a positive cardiac history (angina, CCF,

LVF, hypertension or cardiac medicines) and potassium is less than 4.0 mmol/l give 500 ml 0.9% sodium chloride with 20 mmol potassium by i.v. infusion over 4 hours for each picolax sachet.

3) Check potassium on morning of operation. If less than 3.5 mmol/l inform anaesthetist.

For all resections except TEMS (Trans Endoscopic Micro Surgery)

Patients below 70 years of age;

1) Picolax one sachet orally before 8 a.m. one day pre-op + 500 ml of oral fluids.

2) Picolax one sachet orally between 2 and 4 p.m. one day pre-op + 500 ml of oral fluids.

3) If effluent not clear contact medical staff for advice. 4) Clear fluids for 24 hours pre-op. 5) Nil by mouth for 4 hours pre-op.

Patients aged 70 years and above;

1) Picolax one sachet orally before 8 a.m. one day pre-op + 500 ml Hartmann’s by i.v. infusion over 4 hours.

2) Picolax one sachet orally between 2 and 4 p.m. one day pre-op + 500 ml Hartmann’s by i.v. infusion over 4 hours.

3) If effluent not clear contact medical staff for advice. 4) Clear fluids for 24 hours pre-op. 5) Nil by mouth for 4 hours pre-op.

TEMS or Severe constipation

Patients below 70 years of age

1) Picolax one sachet orally before 8 a.m. two days pre-op + 500 ml of oral fluids.

2) Picolax one sachet orally between 2 and 4 p.m. two days pre-op + 500 ml of oral fluids.

3) Repeat (1) and (2) one day pre-op. 4) If effluent not clear contact medical staff for advice. 5) Clear fluids for 48 hours pre-op. 6) Nil by mouth for 4 hours pre-op.

Patients aged 70 and above; 1) Picolax one sachet orally before 8 a.m. two days pre-op + 500 ml Hartmann’s by i.v. infusion over 4 hours.

2) Picolax one sachet orally at 12 midday two days pre-op + 500 ml Hartmann’s by i.v. infusion over 4 hours.

3) Repeat (1) and (2) one day pre-op. 4) If effluent not clear contact medical staff. 5) Clear fluids for 48 hours pre-op. 6) Nil by mouth for 4 hours pre-op.


Local preparations for anal and rectal disorders Anal and perianal pruritus, soreness and excoriation are best treated by application of bland ointments and suppositories. Careful local toilet as well as adjustment of diet to avoid hard stools is also helpful.

Good evidence is lacking for use of preparations containing local anaesthetics for relief of pain associated with haemorrhoids and pruritus ani.

They may cause more irritation. Prolonged use should be avoided. Lidocaine [lignocaine] ointment may be used before emptying the bowel to

relieve the pain associated with anal fissure.

Soothing haemorrhoidal preparations

Anusol cream/ointment/suppository

One suppository or application of cream/ointment night and morning and after defaecation.

Lidocaine [lignocaine] 5% ointment/ 2% gel

Apply to anal fissure before bowel emptying.

Hydrocortisone 1% cream /ointment

Apply twice daily.

Compound haemorrhoidal preparations with corticosteroids

Anusol HC ointment/suppositories

Use night and morning and after bowel movement.

Proctosedyl ointment/suppository

(s) Surgeons only.

Perinal spray (s) Surgeons only.

Preparations for treating Anal Fissures

Glyceryl trinitrate 0.2% ointment

(s) Unlicensed product. Used two to three times daily.

Diltiazem 2% cream (s) Unlicensed product. Used twice daily for 8 – 12 weeks. Store tube in a fridge.

Rectal Sclerosants

Oily phenol injection (s) Consultants only.

Stoma Care

Stoma Care Nurse RLUH Bleep 4266 and 4269 BGH Bleep 4052


Medicines affecting intestinal secretions

Medicines affecting biliary composition and flow

Ursodeoxycholic acid tablets

(s) Consultants only. Dose for primary Biliary Cirrhosis: 10-15mg/kg/day in 2-4 divided doses.

Pancreatin All pancreatin preparations are for consultant use only.


Management of Patients with Chronic Liver Disease

Introduction Liver disease is a complex area; the involvement of a Hepatologist is strongly advisable. The management of patients presenting with chronic liver disease requires consideration of the following:

Does the patient have acute or chronic disease? Have biliary obstruction and haemolysis been excluded?

Consideration of the underlying cause – removal or treatment of the underlying cause (e.g. alcohol excess, autoimmune hepatitis) can halt or prevent the progression of liver damage

Treatment of the symptoms/complications present - jaundice, ascites, portal hypertension (with or without varices) and encephalopathy

Consideration of altered medicine handling and the need for dosage reduction of medicines in patients with liver disease

Ascites Aims of treatment are to remove fluid with minimal disturbance of electrolytes and without precipitating renal failure. Treatment consists of:

Ensure patients are put on a salt free diet Diuretic therapy:

Spironolactone (a specific aldosterone antagonist): Start at 100mg daily, increase the dose every 3-5 days, max. dose 400mg daily

Furosemide: Use if spironolactone alone ineffective or patient also has peripheral oedema. Start at 40mg daily (max. 160mg daily)

Monitor weight on a daily basis – aim to lose a maximum of 1kg per day (a loss of 0.5-0.75kg/day is adequate in a non-oedematous patient)

Monitor U&Es three times a week initially. Daily U&Es are required for difficult cases. Stop if Cr> 150mmol/L or Na<125mmol/L or K>5.5mmol/L

(spironolactone only) Fluid restriction to 1-1.5L per day if hyponatraemic

Paracentesis: for tense ascites or diuretic-resistant cases of ascites. Consider

if patient receiving in excess of spironolactone 400mg daily. Cover with 100ml 20% albumin solution for every 2-3 litres drained. Stop diuretics the day before and on the day of paracentesis to reduce risk of renal impairment. Never leave a paracentesis catheter in place for more than 12 hours – spontaneous bacterial peritonitis is often not spontaneous.


Spontaneous Bacterial Peritonitis (SBP) Bacterial peritonitis is a specialist subject; advice from a Hepatologist should be sought at the earliest possibility. The decision to treat bacterial peritonitis is based on a neutrophil count in the ascitic fluid > 250 cells/mm3, a positive gram stain culture or both. Signs that the patient may be developing SBP include: sudden abdominal pain, raised temperature, and development of encephalopathy. Patients who have had paracentesis in the last 48 hours have a low threshold for treatment – SBP is often not “spontaneous”.

A Cochrane review concluded that there is no convincing evidence regarding which antibiotic should be used first line and that treatment of SBP is based on clinical experience.1 Initial treatment for confirmed cases according to the hospital antibiotic formulary is piperacillin/ tazobactam IV 4.5g TDS for 5 days.

Secondary prophylaxis – Patients who have had a proven episode of SBP and it has been treated should be given prophylactic ciprofloxacin 500mg OD long term2

There is evidence to support the use of salt poor albumin to reduce the incidence renal impairment and mortality in these patients3. Patients in the study were given 1.5g/kg body weight at the time of diagnosis followed by 1g/kg on day 3.

There is evidence for primary prophylaxis with an ascitic protein count < 10g/l. Under hepatology advice may be started on ciprofloxacin 500mg OD long term.

Variceal Bleed Acute variceal bleeds are associated with a mortality of approximately 30%. Treatment aims to stop bleeding and prevent further bleeds. All patients who are suspected to have experienced an upper GI bleed require urgent endoscopy to diagnose and treat the bleed. Medical management consists of:

Prompt resuscitation – using colloids, blood, platelets IV vitamin K 10mg OD for 3 days if prothrombin time is raised Terlipressin 2mg 4 hourly (given as a slow IV bolus) for up to 72 hours or until

bleeding stops. This has been shown to decrease mortality. Octreotide may be considered for patients with severe vascular disease. The

dosage regime is 1mg made up to 60ml with sodium chloride 0.9% which is then administered over 20 hours – a maximum of 1 infusion per day may be used

Prophylactic antibiotics – Initially piperacillin/ tazobactam IV 4.5g TDS whilst nil by mouth, converting to ciprofloxacin 500mg BD orally when the patient is allowed to eat and drink continued until the patient has received a total of 5 days treatment (IV and oral combined). Antibiotics have been shown to reduce rates of bleeding since it is thought that bacterial translocation may contribute to re-bleeding4

Propranolol should be prescribed for secondary prevention of bleeding varices (and primary prevention of varices identified during routine OGD). Treatment is contra-indicated in patients with asthma. Start at 20mg BD and titrate according to pulse and BP. (Alternative is carvedilol starting at 3.125 – 6.25mg OD)Aim for a resting pulse of 60bpm or a 25% reduction from baseline. Ensure systolic BP remains above 100mmHg


Isosorbide mononitrate is no longer recommended for prophylaxis against variceal bleeds since an increase in mortality has been associated with its use.

Encephalopathy When a patient presents with hepatic encephalopathy, it is important to consider if there are any precipitating causes present. Common precipitants include:

Decompensated liver disease Administration of sedative medicines Infection Electrolyte disturbances Constipation (which may be medicine-induced) Upper GI bleed

The treatment of hepatic encephalopathy involves:

Remove or treat any precipitating factors Lactulose 30-50ml TDS. Aim to produce 2-3 soft motions per day without

causing diarrhoea If patient is NBM or still constipated despite lactulose, prescribe phosphate

enemas BD In resistant cases consider neomycin (gastroenterologist use only). Initially 1g

BD but may be increased to a maximum of 1g QDS. Although absorption is usually minimal, renal function should be monitored along with signs of ototoxicity.

Hepato-renal Syndrome Hepato-renal syndrome is a specialist subject; referral of these patients to a hepatologist is imperative. When a patient develops renal failure secondary to liver disease, it is called hepato-renal syndrome. There are two types:

Type 1: When renal function deteriorates rapidly Type 2: When renal function slowly deteriorates. Type 2 hepato-renal

syndrome may evolve into Type 1 hepato-renal syndrome at any time. In many cases the cause of hepato-renal syndrome is not found, but common precipitants include:

Over-diuresis Infection Major GI bleed Decompensated liver disease

If a patient’s liver disease is corrected, their renal function will return to normal. The treatment of hepato-renal syndrome involves the following:

Stop diuretic therapy (if prescribed) Rehydrate as necessary –unless advised otherwise by gastroenterologists

avoid intravenous sodium chloride Start terlipressin 0.5-2mg QDS with 100ml albumin 20% per day. Monitor renal function daily, stop terlipressin once renal function has

recovered.


Medicine Use in Liver Disease When faced with treating a patient who has liver disease for other conditions, two questions are often raised

Is medicine X safe to use in liver disease? Does medicine X require a dosage reduction?

Medicine dosing in liver disease Medicine dosing in liver disease is not as easy to predict as that for renal disease. Consideration should be paid to how the medicine is eliminated (hepatic versus renal) and how it is distributed (e.g. binding to albumin). The general rule is to use the lowest effective dose at the longest interval possible and titrate according to clinical response. For further advice regarding medicine choice and dosing in liver disease contact either your ward pharmacist or medicines information (ext: 2096).


Medicine Choice in Chronic Liver Disease The table below discusses the use of medicines for specific indications in patients with liver disease. Please note that this list is NOT exhaustive. Indication Medicine of choice

Analgesia Paracetamol may be used, but use half the dose Small doses of opiates (e.g. codeine 30mg BD-TDS) may be

added (providing the patient is not encephalopathic). Ensure the patient does not become constipated (prescribe prophylactic senna and lactulose during treatment with such medicines)

Avoid NSAIDs if patient is jaundiced or has liver disease

Infection Avoid flucloxacillin and co-amoxiclav if the patient has previously experienced cholestatic jaundice/hepatic dysfunction to either one of these

Erythromycin may worsen hepatic function – monitor LFTs closely if used in patients with liver disease

Hypertension Most agents are considered safe: ACE inhibitors and angiotensin receptor antagonists may be used,

but monitor potassium closely if concurrently prescribed spironolactone since patient could become hyperkalaemic

Beta blockers – atenolol may be preferable (unless the patient has varices) since it is renally cleared

If the patient is receiving loop diuretic therapy, it may be prudent to avoid thiazide diuretics since this combination can result in a profound diuresis

Depression Paroxetine is preferred owing to its shorter half-life

Epilepsy Phenytoin – A lower dose may be needed due to reduced hepatic metabolism and lower serum albumin levels

Avoid sodium valproate

Diabetes Insulin Sulphonylureas may cause hepatotoxicity Thiazolidinediones (pioglitazone and rosiglitazone) should be

avoided in liver disease

Anxiety Oxazepam (short-acting, not extensively metabolised by the liver)

Psychosis Haloperidol – not generally associated with liver toxicity, but use with caution since it may precipitate coma. Dose should be reduced

References

1. Soares-Weiser K, Brezis M, Leibovici L. Antibiotics for spontaneous bacterial peritonitis in cirrhotics (Review). The Cochrane Collaboration 2005

2. Moore KP and Aithal GP. Guidelines in the management of ascites in cirrhosis. British Society of Gastroenterology Guidelines. Gut 2006;55;1-12

3. Sort P, Navasa M, Arroyo V et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999; 341:403-9

4. Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding (Review). The Cochrane Collaboration 2005-08-17


CARDIOVASCULAR SYSTEM Contents (Click on heading to go to that section)

Positive Inotropic medicines

Cardiac glycosides Phosphodiesterase Inhibitors

Diuretics

Thiazide Diuretics Loop Diuretics Potassium Sparing Diuretics Potassium sparing diuretics with other diuretics Osmotic Diuretics

Anti - arrhythmic Medicines

Management of Arrhythmias Atrial Fibrillation Atrial Flutter Ventricular Tachycardia Supraventricular and Ventricular Arrhythmias Ventricular Arrhythmias Bradycardias

Beta - adrenoreceptor Blockers

Medicines affecting the renin-angiotensin system and some other antihypertensive medicines

Management of Hypertension Hypertensive crisis Use of Antihypertensive Medicines in Patients With Co - existing Disease Vasodilator antihypertensive medicines Alpha - adrenoreceptor blocking medicines Management of Heart Failure Medicines affecting the Renin-Angiotensin system

Nitrates, calcium-channel blockers, and potassium channel activators

Nitrates Calcium - channel Blocking Medicines Peripheral and Cerebral Vasodilators

Sympathomimetics

Inotropic Sympathomimetics Vasoconstrictor Sympathomimetics Cardiopulmonary resuscitation

Anticoagulants and protamine

Prophylaxis of Venous Thromboembolism Treatment of Venous Thromboembolism


Guidelines for the Management of Pulmonary Embolism and Deep Vein Thrombosis Parenteral anticoagulants How to Use Intravenous Heparin in Adults Oral Anticoagulants Management of over - anticoagulation With Warfarin Anticoagulant Clinic/ Long Term Anticoagulation Protamine sulphate

Antiplatelet Medicines

Myocardial Infarction and fibrinolysis

Primary Prevention of Myocardial Infarction Secondary Prevention of Myocardial Infarction Non ST Elevation Acute Coronary Syndromes ( NSTEACS ) Guideline Pathway from diagnosis to coronary angiogram Fibrinolytic Medicines

Antifibrinolytic Medicines and Haemostatics Lipid - regulating Medicines Local Sclerosants


Positive Inotropic Medicines

Cardiac glycosides

Digoxin tablets/syrup/injection

Used for supraventricular arrhythmias and in the management of heart failure Supraventricular arrhythmias Loading doses are sometimes omitted depending on the clinical status of the patient. Oral digitalisation: Digoxin 500micrograms stat followed by 250micrograms every 8 hours for 3 further doses if required Intravenous digitalisation: By i.v. infusion, 750 – 1000 micrograms in 50mL sodium chloride 0.9% or glucose 5% over at least two hours (maintenance dose to be started the following day) Or 250micrograms in 50mL sodium chloride 0.9% or glucose 5% over 30mins. Give a further 250micrograms 1 hour later. Repeat after 2 hours if necessary. Maintenance oral dose: 62.5 - 500micrograms daily according to age and renal function. Heart failure Used in heart failure as digoxin is a positive inotrope. There is no need for a loading dose. Maintenance oral dose: 62.5 - 250micrograms daily according to age and renal function. Patients may still benefit even if level is less than the recommended therapeutic range Click here for therapeutic level monitoring.

Phosphodiesterase Inhibitors

Enoximone injection (s) Cardiologists (CCU) and Anaesthetists only.


Diuretics Thiazide Diuretics

Bendroflumethiazide tablets

Hypertension: 2.5mg each morning

Indapamide tablets (thiazide like diuretic)

Hypertension (in preference to bendroflumethiazide as initial

treatment of primary hypertension): 2.5mg each morning

Metolazone tablets Added into loop diuretics treatment (synergistic effect) to treat persisting oedema. (Dose range 2.5mg alternate days - 5mg od) Note: Profound diuresis may occur in combination with loop diuretics. Review use before patient is discharged. Monitor plasma electrolytes and weight regularly.

Loop Diuretics

Furosemide [frusemide] tablets/liquid/injection

Oedema: By mouth, initially 40mg in the morning, increasing to 80 - 160mg once or twice daily. Do not give dose after 6pm unless patient is catheterised. Oliguria: By mouth, initially 250mg daily increasing in steps of 250mg every 4 - 6 hours to max. dose of 1.5g in 24 hours. 250mg by injection can be considered approximately equivalent to 500mg orally. Therefore do not prescribe as po/iv because the formulations are not bioequivalent By i.v. injection, initially give 20 - 50mg slowly at max. recommended rate of 4mg/min. The risk of ototoxicity is related to the rate of administration. By i.v. infusion, 250 - 500mg. May be diluted in 50 - 100mL sodium chloride 0.9% (not glucose) for infusion. Max. rate 4mg/min. Sometimes a continuous infusion is given eg.250mg in 50ml given at 2ml/hr via syringe pump.


Bumetanide tablets/liquid/injection

Note: furosemide [frusemide] 40-60mg orally is approximately equivalent to bumetanide 1mg orally. Oedema: By mouth, 1mg in the morning increasing to 2 -4mg once or twice daily. In elderly patients 500micrograms daily may be sufficient. Bumetanide injection is only indicated if patient is intolerant to Furosemide. By i.v. injection, 1 - 2mg given over 1 -2 minutes repeated after 20mins if necessary. By i.v. infusion, 2 - 5mg diluted in 50 to 100mL glucose 5% or sodium chloride 0.9%. 3mg given over 30mins, 4mg over 45mins and 5mg over 60mins

Potassium Sparing Diuretics and Aldosterone antagonists The diuretic effects of potassium sparing diuretics are additive to those of thiazide and loop diuretics. They cause retention of potassium and are used as an alternative to giving regular potassium supplements with thiazide or loop diuretics. The retention of potassium is more effective than potassium supplementation. Potassium sparing diuretics are not usually required alongside the treatment of hypertension with thiazide diuretics unless hypokalaemia occurs.

Amiloride tablets/liquid With other diuretics: 5 - 10mg daily. Alone: 10mg daily Max. 20mg daily.

Spironolactone tablets Low doses of spironolactone (usually 25 - 50mg daily) may be considered for patients with severe heart failure (severe LVSD) who are already receiving an ACE inhibitor.

Eplerenone tablets (s) Licenced for heart failure (LVEF< 40% and clinical signs) post myocardial infarction. To be started within 3- 14 days of the event. Starting dose 25mg daily titrated up to 50mg daily. Restricted to cardiology use only


Potassium sparing diuretics with other diuretics Combination products should be reserved for patients who have a problem with compliance. It is preferable to administer potassium sparing diuretics (or indeed potassium supplements) separately if needed unless treatment is unlikely to change.

Co - amilozide tablets (Amiloride hydrochloride 2.5mg or 5mg plus hydrochlorothiazide 25mg or 50mg) Hypertension: 1 - 4 tablets in the morning of 2.5/25 strength or 1 - 2 tablets of 5/50 strength increased if necessary to a max. of 4 daily of 5/50 strength.

Co - amilofruse 5/40 tablets

(Amiloride 5mg plus furosemide [frusemide] 40mg) 1 – 2 tablets daily Please specify strength of tablet as also available as 2.5/20

Osmotic Diuretics

Mannitol Injection (s) Consultants only.

Anti - arrhythmic Medicines

Management of Arrhythmias Note: Medicine treatment for SVT or VT is not appropriate if marked hypotension is present (systolic BP < 90mmHg) with cardiac failure or poor peripheral, renal or cerebral perfusion. DC conversion is treatment of choice in these circumstances. See entry under individual medicines for more details on dosage and administration.


Initial Treatment of Acute Arrhythmias

Supraventricular Tachycardias (SVT)

1) Adenosine 3mg by rapid i.v. bolus (inject over less than 2 seconds into a large vein with cardiac monitoring) followed by 6mg after 1 - 2 minutes if necessary

and then by 12mg after a further 1 - 2 minutes Do not use in asthmatic patients (If given through an iv line rather than a cannula it should be

followed by a sodium chloride 0.9% flush) 2) Verapamil 2.5 - 10mg by slow iv injection (inject slowly

over 2 mins with ECG monitoring). Do not use with / after beta - blockers or in possible

ventricular tachycardia or atrial fibrillation with pre-excitation e.g. Wolff Parkinson White syndrome. Do not use in broad complex tachycardia unless under the direct supervision of a consultant cardiologist.

Atrial Fibrillation 1) Beta-blockers 2) Digoxin 3) Amiodarone (click here for administration policy) 4) Dronedarone- this is not yet approved for use but is

under review by the medicines management team Patients should also be anticoagulated if not contraindicated once rhythm has been confirmed. Click here for further details on management.

Ventricular Tachycardia If sustained and patient is haemodynamically compromised use DC shock. If unsustained or patient is haemodynamically stable or there is a delay to DC shock use

1) Amiodarone 2) Lidocaine [lignocaine] i.v. (ready diluted infusion bags

4mg/ml are available for use) Consider use of intravenous magnesium sulphate especially if Torsades de pointes present, (click here for dosage).

Chronic and Recurrent Supraventricular Arrhythmias

1) Digoxin 2) Verapamil or beta - blockers if LV function is good 3) Flecainide 4) Amiodarone

Paroxysmal Atrial Fibrillation and SVT

Good LV function: 1) Sotalol 2) Flecainide 3) Disopyramide

Impaired LV function: 1) Amiodarone


Recurrent Symptomatic Ventricular Arrhythmias

1) Sotalol 2) Amiodarone 3) Flecainide 4) Propafenone

Atrial Fibrillation Options are rate control or rhythm control.

Rhythm control NB Only for patients who have been in atrial fibrillation for less than 48 hours. If not seek specialist advice regarding TOE guided cardioversion Options:

1) DC shock 2) Betablockers (including sotalol) 3) Amiodarone 4) Flecainide (contraindicated if known or suspected structural heart disease

/IHD/ previous MI) 5) Dronedarone – non formulary- requests by consultant cardiologists will be

considered on an individual patient basis due to concerns over side effect profile.

Rate control Options:

1) Betablockers (not sotalol) 2) Rate limiting calcium channel blockers (verapamil or diltiazem- as alternative

to betablockers) 3) Digoxin 4) Amiodarone

Warfarin should be considered for patients at high risk of developing stroke unless contra – indicated and is required for patients prior to DC cardioversion if AF persistent for greater than 48 hours. For immedicate anticoagulation for AF, dalteparin at a dose of 200units/kg daily can be given. See here for algorithm of dalteparin doses. See also NICE guidance on the treatment of AF. http://www.nice.org.uk/nicemedia/live/10982/30055/30055.pdf Pill in the pocket approach with flecainide may be suitable for some patients (Consultant cardiologist prescribing only).


http://www.nice.org.uk/nicemedia/live/10982/30055/30055.pdf

Atrial Flutter Medications as for atrial fibrillation as above. NB- more likely to respond to DC cardioversion than chemical cardioversion. Patients also need to be considered for anticoagulation as for Atrial Fibrillation.

Management of Known or Strongly Suspected Digoxin Overdose

Digibind injection (s) Consultants only. After advice from Poisons Information Service. For use where measures beyond withdrawal of cardiac glycoside; correction of electrolytes and fluid balance are also necessary.

Ventricular Tachycardia

Magnesium sulphate 50% injection

2mmol magnesium/mL (1g in 2mL). This schedule is for treatment of serious arryhthmias including torsades de pointes. By i.v. Infusion, Give 8mmol (4ml of 50% injection) over 10 - 15mins. CCU protocol: Add 20mmol (10ml of 50% injection) to 250ml glucose 5% and infuse intravenously over 30 mins


Medicines for Supraventricular and Ventricular Arrhythmias

Amiodarone tablets/injection

By mouth: Loading regimen, 200mg 3 times daily for 7 days, reduced to 200mg twice daily for a further seven days before the maintenance dose. Unlicensed loading regimes (only to be prescribed by consultant cardiologists) may be used e.g. 400mg bd until patient has received 10g, then reduced to 200mg daily Maintenance dose: 200mg daily or minimum required to control arrhythmia. Significant toxicity may develop when doses above 200mg a day are used for maintenance. Guidelines for iv administration of amiodarone Initial dose 300mg followed by 900mg infusion if required (Maximum 1.2g in maximum volume of 500ml in 24 hours) 300mg: Given as slow iv injection over 3 minutes (in extreme emergency) as per cardiac arrest protocol with ECG monitoring (minijet pre- filled syringe) into large ante cubital vein Or iv infusion in 250ml glucose 5% over 30 minutes preferably via central line 900mg: iv infusion in 500ml glucose 5% over 23.5 hours via central line or long line The decision to give via a peripheral line must be discussed with the consultant for that patient or the on call consultant. The reasons for this decision should be documented in the patient’s medical notes.

Notes: Patients should be advised of the potential side effects of amiodarone Many patients taking amiodarone develop corneal deposits (reversible on discontinuation). There is a rare risk of optic neuritis and blindness. Warn drivers that car headlights may dazzle them at night.

Amiodarone may cause phototoxic reactions. Advise patients to use a total sunblock that blocks both UVA and UVB light when

exposed to the sun, e.g. Uvistat 30. Amiodarone can cause disorders of thyroid function. Laboratory tests should be performed before prescribing, (or as soon as possible

after initiation) and at least every 6 months. Patients must be counselled about the risk of irreversible pulmonary fibrosis. This

should be documented in the patient's notes. Pneumonitis should be considered if new or progressive shortness of breath or

cough develops in patients taking amiodarone. Liver function should be monitored pre - treatment and at 6 monthly intervals

thereafter.


Disopyramide capsules/ m/r tablets/injection

By mouth, 300 - 800mg daily in divided doses. Slow release tablets 250 - 375mg twice daily. By i.v. injection, 2 mg/kg over at least 5 mins (max. rate 30mg/min) to max. 150 mg, with ECG monitoring, followed immediately by either 200mg orally then 200mg every 8 hours for 24 hours or 400micrograms/kg/hr by intravenous infusion in sodium chloride 0.9%, or glucose 5% (max 800mg in 24 hours) Max. 300mg in first hour, and 800mg daily.

Flecainide (s) tablets/injection

Cardiologists only. By mouth: 50-100mg bd (max 300mg daily) By injection: 2mg/kg (to max 150mg) iv infusion over 30 mins via syringe pump (may be diluted with glucose 5%). If continuous infusion is needed afterwards please see product information.

Oral beta-blockers See beta-blocker section of formulary here

Rate limiting calcium channel blockers

Click here for iv and here for oral treatments

Propranolol injection (s) Cardiologists and Anaesthetists only.

Atenolol injection (s) Cardiologists and Anaesthetists only or as part of myocardial infarction pathway

Metoprolol injection (s) Cardiologists and Anaesthetists only.

Quinidine bisulphate s/r tablets (s)

Cardiologists only.

Sotalol tablets (s) Cardiologists and Consultants only.

Esmolol injection (s) Cardiologists and Anaesthetists only. Protocol for administration for arrhythmias available in CCU

Procainamide (s) tablets/injection

Cardiologists and Anaesthetists only. Unlicensed treatment available only from special import companies and requires a consultant responsibility form


Ajmaline injection (s) Cardiologists only for diagnosis of Brugada's syndrome Unlicensed treatment available only from special import companies and requires a consultant responsibility form

Ventricular Arrhythmias

Amiodarone See here

Propafenone tablets (s) Cardiologists only.

Lidocaine [lignocaine] Injection

DO NOT give if any form of heart block is present. In patients without gross circulatory impairment: By slow i.v. injection, 100mg over a few minutes followed by infusion 4mg/minute for 30 minutes, 2mg/minute for 2 hours then 1mg/minute. Further reduce if infusion lasts beyond 24 hours

Available as a pre-filled bag, 0.4% lidocaine in 500ml dextrose 5% (equivalent to 4mg /ml)

REQUIRED DOSE RATE OF INFUSION

1 mg/min 15ml/hr

2mg/min 30ml/hr

3mg/min 45ml/hr

4mg/min 60ml/hr

Bradycardias Discontinue any medicines that may worsen or precipitate bradycardia

Atropine sulphate injection

For management of bradycardias especially if complicated by hypotension: By IV injection, initial dose 300 micrograms, followed by 100 microgram increments (up to max 600 micrograms in 1 dose) at 3-5 minute intervals as required. Total dose should not exceed 0.03mg/kg (2mg) in patients with mild bradycardia or 0.04mg/kg (3mg) in patients with severe bradycardia as this dose generally results in complete vagal blockade

Isoprenaline (S) For the support of the heart rate in those awaiting definative management of bradycardia and in the treatment of Torsades de Pointes. Only to be used by consultant cardiologists


Beta - adrenoreceptor Blockers

All beta - blockers are contra - indicated in patients with A) Asthma B) Uncontrolled heart failure C) Sick sinus syndrome D) Second or third degree heart block E) Cardiogenic shock

Beta - blockers should be used with caution in patients with

A) History of obstructive airways disease (consider reversibility testing prior to initiation of a cardioselective betablocker)

B) Peripheral vascular disease C) Diabetes

NB. Beta-blockers are no longer recommended first line for hypertension (NICE guidance) In heart failure patients, beta-blockers licensed for heart failure should only be initiated when patients are stable and not in acute heart failure. They should be initiated by specialists in heart failure and should be started at a low dose and titrated up very gradually over a number of weeks to the target (or maximum tolerated) dose.

Beta-Blocker (Alphabetical Order)

Licenced Indication Doses

Angina Tablets: 50-100mg daily

Arrhythmias Tablets: 50-100mg daily

Atenolol tabs/liquid (injection – consultant only or as part of the MI pathway)

Immediately post MI Injection: iv bolus 2.5- 5mg as single dose injected over 5 minutes

Angina and post MI

Max 10mg daily Bisoprolol tabs (cardioselective)

Stable moderate to severe heart failure

Start at 1.25mg daily and titrate up gradually to 10mg daily

Angina Start at 12.5mg bd and increase if tolerated to 25mg bd

Carvedilol tabs (non-cardioselective)

Heart failure Start at 3.125mg bd and titrate gradually to max 25mg bd (50mg bd if >85kg)

Arrhythmias

Esmolol injection (cardiologists and anaesthetists only)

Hypertension

Continuous infusion Protocol available on CCU/ HEC for administration


Beta-Blocker Licenced Indication Doses (Alphabetical Order)

Hypertensive crisis Labetolol injection (consultants and anaesthetists only)

Aortic dissection

See ITU protocol and product information

Nebivolol tabs Cardiologists only (very cardioselective)

Heart failure (but bisoprolol and carvedilol are first line for heart failure –regional protocol)

1.25mg daily titrated gradually up to max 10mg daily

Portal hypertension 40mg bd increased as necessary to max 160mg bd SR preparations may be used once daily.

Arrhythmias

10-40mg tds

Propranolol tabs/ SR caps

Anxiety (palpitations/sweating)

40mg od increased to tds as necessary

Ventricular arrhythmias

Sotalol tabs

Prophylaxis of paroxysmal SVTs

Initially with ECG monitoring, and checking of QTc interval 80mg od (or 40mg bd) increased as necessary max usually 160mg bd


Medicines affecting the renin-angiotensin system and some other antihypertensive medicines

Management of Hypertension The choice of initial agent should be decided according to age and ethnicity and co-existing disease states. The table below taken from NICE guidance August 2011 on hypertension (http://www.nice.org.uk/nicemedia/live/13561/56015/56015.pdf) summarises the initial treatment of primary hypertension (not including patients with Type 2 diabetes or Chronic Kidney Disease).



Further advice on the management of hypertension, based on the NICE guidelines, can be found in section 2.5 of the current B.N.F or use the link above. Antihypertensive agents:

Thiazide Diuretics (click here) Calcium - channel blockers (click here) Angiotensin converting enzyme (ACE) inhibitors (click here) Angiotension II receptor blockers (ARBs) (click here) Alpha – blockers (click here) Beta – blockers (click here) Other Vasodilators (click here)

The optimal treatment targets are:

systolic blood pressure < 140mmHg and diastolic blood pressure < 90mmHg The targets for patients with diabetes, chronic renal disease or established atherosclerotic cardiovascular disease are:

systolic blood pressure < 130mmHg and diastolic blood pressure < 80mmHg In all hypertensive patients non - pharmacological measures should also be employed e.g. reducing sodium intake, stopping smoking and reducing stress. The table below (click here) summarises the main indications and contraindications for the different classes of antihypertensive medicines. Sub-maximal doses of two medicines result in larger reductions in blood pressure and fewer side effects than maximal doses of a single medicine. In more severe hypertension, medicines may be added in a stepwise manner as per NICE recommendations until the blood pressure is controlled. If blood pressure falls below the optimal levels, treatment can be stepped down accordingly. Aspirin 75mg daily is recommended for secondary prevention of cardiovascular events. For primary prevention in patients over the age of 50, cardiovascular risk prediction charts (at the back of the BNF) can be used to assess a patient’s risk of cardiovascular disease over the next 10 years. Any patient with a risk score >20% should be assessed as to whether they need aspirin 75mg daily for primary prevention (unlicensed use) This decision should be made on an individual patient basis taking into account all the risks and benefits. Hypertensive patients with hypercholesterolaemia who have a high risk of coronary heart disease may benefit from a statin (click here)


Hypertensive crisis Seek specialist advice

Medication options include iv Labetalol iv Esmolol iv Sodium nitroprusside

Use of Antihypertensive Medicines in Patients With Co - existing Disease

Indication Contraindications

Class of medicine

Compelling Possible Possible Compelling

Thiazides Secondary prevention of stroke

- - Gout

Beta - blockers Post MI Angina Some Tachy-

Arrhythmias

Heart failure1 Heart failure1 Peripheral

vascular disease (caution only)

COPD (caution only)

Asthma Heart block

Calcium channel blockers (rate limiting)

Angina Myocardial infarction

Combination with beta - blockers

Heart block Heart failure

ACE inhibitors Heart failure Left ventricular

dysfunction Post MI Established CHD Diabetic

nephropathy Secondary

prevention of stroke

Chronic renal disease2

Renal impairment2

Peripheral vascular disease4

ACE Inhibitor induced dry cough3

Pregnancy Bilateral

renal artery stenosis

Alpha - blockers Prostatism Postural hypotension

Heart failure

Urinary incontinence

Adapted from: British Hypertension Society Guidelines 2004 Journal of Human Hypertension (2004) 18: 139-185


Notes: 1) Beta - blockers may worsen heart failure, but may be used by specialists to

treat heart failure, (bisoprolol, carvedilol and nebivolol only). 2) ACE inhibitors may be beneficial in chronic renal failure but should be used

with caution. Close supervision and specialist advice are needed when there is established and significant renal impairment.

3) ACE Inhibitor induced dry cough: an angiotensin II – receptor antagonist may be tried.

4) Peripheral vascular disease: Use ACE inhibitors and angiotensin II receptor antagonists with caution in peripheral vascular disease due to the possibility of undiagnosed or clinically silent reno-vascular disease.

5) Alpha – blockers: should not be used as monotherapy in the absence of another clear indication for use.

Vasodilator antihypertensive medicines

Sodium nitroprusside Injection (s)

Cardiologists and Anaesthetists only. Protocol available on CCU. ITU and other HDU areas have their own protocol according to consultant anaesthetist guidance

Hydralazine Used in combination with nitrates for the treatment of heart failure as per NICE guidance (CG108 August 2010) Usual starting dose 25mg bd- tds titrated up to max 75mg qds with concurrent nitrate therapy (usually isosorbide mononitrate tablets) Cardiologists only

Alpha - adrenoreceptor blocking medicines

Doxazosin tablets / MR tablets

Hypertension: 1mg daily, increased after 1 – 2 weeks to 2mg daily, and thereafter to 4mg daily. Max. 16mg daily. Doxazosin XL (modified release tablets) : Starting dose 4mg od increase to max 8mg daily after 4 weeks if necessary

Tamsulosin MR See urology section of the formulary

Alfuzosin tablets/ MR tablets

See urology section of the formulary

Phenoxybenzamine (s) capsules/injection

Consultants and Anaesthetists only.

Phentolamine Injection (s)

Anaesthetists only.


Management of Heart Failure Chronic Heart Failure

Preparations

Diuretics (click here)

ACE inhibitors (click here)

Beta – blockers (click here)

Aldosterone antagonists (click here)

Digoxin (click here)

Hydralazine and nitrates (click here)

Angiotension II receptor antagonists (ARBs)

(click here)

See also NICE guidelines for Chronic Heart Failure CG108 (http://www.nice.org.uk/nicemedia/live/13099/50526/50526.pdf) Acute Heart Failure Preparations

Diuretics (click here)

Intravenous Nitrates (click here)

Inotropic sympathomimetics (click here)



Medicines affecting the Renin-Angiotensin system Angiotensin Converting Enzyme (ACE) Inhibitors

In volume depleted patients any diuretic should be discontinued or the dose reduced significantly, 2 - 3 days before initiation of an ACE inhibitor. This may not be desirable however in heart failure patients.

A small initial dose of an ACE inhibitor may be used as a test dose usually given in the evening. However this isn’t always necessary. Medical supervision is recommended for at least 2 hours after the first ACE inhibitor dose has been given or until the patient’s blood pressure has stabilised.

ACE inhibitors are contraindicated in patients with bilateral renal artery stenosis as they are likely to cause acute renal failure.

ACE inhibitors may cause progressive impairment of renal function and hyperkalaemia. Therefore monitor renal function closely and titrate dose carefully in all patients particularly those with renal impairment.

Do not give with potassium sparing diuretics unless potassium levels are monitored closely.

ACE inhibitors are recommended first line for all patients with heart failure due

to left ventricular systolic dysfunction (LVSD).

Other indications are hypertension, diabetic nephropathy and secondary prevention of CVD.

In hospital, ACE inhibitors are often titrated up more quickly than

recommended in the BNF (shown above) however it is important for all patients to have their BP and renal function monitored closely especially before and after any dose change.

If tolerated ACE inhibitors should be titrated up to the maximum recommended

dose for heart failure, secondary prevention and nephropathy.


Perindopril erbumine (tert butylamine) tablets

Hypertension: initially 4mg daily (elderly 2mg daily) max 8mg daily Heart failure: 2mg daily increasing to 4mg daily There are also perindopril arginine tablets with doses of 2.5mg and 5mg but RLBUHT doesn’t stock these.

Ramipril tablets/capsules

Hypertension: Initially 1.25mg daily increased at intervals of 1 - 2 weeks. Max. 10mg daily Heart failure: Initially 1.25mg daily increased at intervals of 1 – 2 weeks. Max 10mg daily Prophylaxis of cardiovascular events or stroke: Initially 2.5mg daily increased after 1 week to 5mg daily, increased after 3 weeks to max 10mg daily. Prophylaxis after myocardial infarction: (started 48 hours after MI), initially 2.5mg twice daily, increased after 2 days to max 5mg twice daily. Nephropathy: initially 1.25mg daily increased after 2 weeks to 2.5mg daily then increased after a further 2 weeks to 5mg daily.

Angiotensin II - receptor Antagonists (ARBs) There is some evidence to show that this group of medicines are effective treatments for hypertension however they are recommended only when patients are unable tolerate ACE inhibitors due to side effects (e.g. a problematic cough) or in preference to an ACE inhibitor in person of African or Caribbean family origin (as per NICE Hypertension guidelines August 2011). There are also 3 angiotensin II receptor antagonists licenced for heart failure, candesartan, valsartan (post MI) and losartan but again ACE inhibitors would be first line treatment unless patient is intolerant. The combination of an ACE inhibitor and an angiotensin II receptor antagonist has been shown to be effective in some clinical trials for heart failure caused by left ventricular systolic dysfunction, but should only be initiated by a specialist in that area (i.e. consultant) and is a second line treatment. The use of ACE inhibitor and ARB together for hypertension is not recommended.


Candesartan tablets RLBUHT formulary choice ARB for heart failure

Licenced for Heart Failure with impaired LV function / hypertension Hypertension : Initially 4- 8mg once daily (2mg in hepatic impairment) adjusted according to response to max 32mg daily. Usual maintenance 8mg once daily. Heart failure: Initially 4mg daily titrated to target dose (max) 32mg daily Contraindicated in cholestasis

Valsartan capsules Only recommended by

RLBUHT for heart failure post MI or post MI if intolerant of ACE inhibitors

Left ventricular systolic dysfunction post MI Heart failure: initially 40mg bd increased at intervals up to max 160mg bd For post MI – 20mg BD increasing to 160mg BD

Losartan tablets Licenced for hypertension / diabetic nephropathy in Type 2 DM/ heart failure Used in RLBUHT for hypertension and nephropathy Hypertension and nephropathy: 50mg once daily (25mg initially for elderly and those with severe renal impairment) increased if necessary to max 100mg daily

Irbesartan tablets Licenced for hypertension Dose: 150mg once daily, increased if necessary to 300mg once daily (in haemodialysis or patients over 75 years, an initial dose of 75mg may be used).

It is important to remember that Angiotensin II receptor antagonists have many of the same cautions and contraindications as ACE inhibitors and therefore it is important to closely monitor renal function, potassium and BP especially before and after any dose change.


Nitrates, calcium-channel blockers, and potassium channel activators Management of Angina In addition to aspirin, statins and ACE inhibitors for patients with known ischaemic heart disease there are also anti-anginal agents available. They should be added in a stepwise manner. 1st line anti-anginals – rate controlling

Betablockers (click here) Rate limiting calcium channel blockers eg diltiazem (click here)

2nd line antianginals – if 1st line agents contraindicated or not controlling angina

Dihydropyridine calcium channel blockers (click here) Patients can receive a combination of up to 3 second line anti-anginals 3rd line antianginals – only to be prescribed by cardiologists if 1st and 2nd line agents

are contraindicated or not controlling angina

Nitrates (click here) Nicorandil (click here)

4th line antianginals – only to be prescribed by cardiologists and if 1st / 2nd and 3rd

line agents are contraindicated or not controlling angina Ivabradine (S) (click here) Ranolazine (S) (click here)

Management of Acute Coronary Syndrome (click here) Nitrates Glyceryl trinitrate Some form of sublingual GTN should be prescribed ‘when required’ for all patients presenting with suspected angina if no contraindications.


Sublingual tablets: 300 - 500micrograms `when required'

Sublingual Spray: 1 - 2 sprays (400 microgram per spray) `when required'

Buccal tablets: Can be prescribed when sublingual GTN isn’t strong enough to relieve anginal pain and can be considered as an alternative to IV nitrates. They are not routinely prescribed as discharge medication unless the patient has refractory angina and it has been specified by consultant cardiologist The tablet should be placed between upper lip and gum (not sublingually) and left to release the medicine. Angina: 2 - 3mg BUCCALLY `when required'. Left ventricular failure: 5mg 3 times daily as alternative to IV infusion of nitrates. May be increased to 10mg 3 times daily in severe biventricular failure. Requires close BP monitoring.

Isosorbide mononitrate It is important to remember that patients require a nitrate free period (6-8 hours) when taking regular nitrates as prophylaxis of angina. Therefore immediate release isosorbide mononitrate/ dinitrate should be prescribed morning and afternoon. MR preparations should only be prescribed once daily.

Isosorbide mononitrate tablets / MR tablets, capsules

For angina and adjunct in congestive heart failure Initially 20 - 40mg twice daily (10mg twice daily in those who have not previously received nitrates). Increased to max 40mg tds with last dose no later than 6pm. Modified release preparations are only given once daily. Usual starting dose 30mg MR once daily. Increased to max 120mg once daily


Isosorbide dinitrate infusion 0.05%

Angina: By IV infusion, 2 - 10mg/hr (up to 20mg/hr). Start at 2mg/hr and increase according to response. There is a nurse monitoring sheet available for documentation of dose changes and instructions on titration rate. Left ventricular failure: By IV infusion, 2 - 10mg/hr (up to 20mg/hr). Start at 2mg/hr and increase according to response. NB Formulary may change to GTN infusion instead of isosorbide dinitrate infusion in the future.

Preparation of isosorbide dinitrate for infusion:

Maximum concentration for peripheral administration is 500micrograms/mL (0.05%) which may be administered without further dilution via a syringe pump.

If there is no 0.05% available dilute 30mL of 0.1% (1000 micrograms/mL) to 60mL with glucose 5% or sodium chloride 0.9% to create a 0.05% solution and administer via a syringe pump.

Higher concentrations – 1000 micrograms/ml (0.1%) may be given via a central IV line only. Isosorbide dinitrate infusion is incompatible with PVC administration sets.

Potassium Channel Activators

Nicorandil Angina: 10mg twice daily, can be increased up to a maximum of 30mg twice daily.

Calcium - channel Blocking Medicines Used for hypertension, angina and post MI (diltiazem). Nimodipine is used for the treatment of subarachnoid haemorrhage.

Rate limiting calcium channel blockers Should be avoided in heart failure due to negative inotropic effects

Diltiazem tablets/ m/r tablets/capsules

Brand of tablets should be specified as the different preparations have different bioavailabilities Start at lowest dose and titrate up as required.


FORMULARY CHOICE BRAND DOSE AND FREQUENCY

Twice daily modified release preparations

Tildiem Retard *

90 - 180mg twice daily

(max dose for angina 240mg bd)

Once daily modified release preparations

Tildiem LA *

200 - 300mg once daily (max dose 400- 500mg daily)

Verapamil tablets/ m/r tablets/liquid

Verapamil should not be used in conjunction with beta blockers Angina: 80 - 120mg 3 times daily. Supraventricular arrhythmias: 40 - 120mg 3 times daily Hypertension: 240 - 480mg daily in 2 - 3 divided doses. Modified release preparations (should be prescribed by brand where possible): Half Securon SR 120mg daily. New patients to start on this dose then may be changed to Securon SR Max. 2 tablets twice a day. Securon SR 240mg daily, increased to 1 tablet twice a day. Modified release preparations are not licenced for supraventricular arrhythmias

Dihydropyridine calcium channel blockers

Amlodipine tablets Has less negative inotropic activity therefore preferred choice in presence of heart failure. Hypertension and Angina: Initially 5mg once daily. Max. 10mg once daily.

Felodipine tablets Hypertension and Angina: Initially 5mg once daily increased if necessary to 10mg once daily.

Nifedipine Immediate release nifedipine is no longer recommended as they are associated with large variations in blood pressure and reflex tachycardia. Hypertension: Adalat LA- 20mg-30mg once daily increased if necessary to max 90mg once daily Not usually used for angina prophylaxis- amlodipine or felodipine preferred.


Management of Subarachnoid Haemorrhage

Nimodipine injection (10mg/50mL) For treatment (iv infusion): Must be administered via syringe pump connected via a Y-site connection into a running drip (40mL/hr) of either sodium chloride 0.9% or glucose 5% as a co-infusion into central IV line. Must be non- PVC. Infusion should be protected from light. Nimodipine must not be added to the infusion fluid or mixed with any other medicines. Blood pressure must be closely monitored. If central IV line administration is not possible, double the rate of the co - administered infusion fluid to 80mL/hr (N.B. this is an unlicensed method of administration). Dose: For patients > 70kg and with stable blood pressure 1mg/hr (5mL/hr) initially, increased after 2 hours to 2mg/hr (10mL/hr) providing the patient is not hypotensive For patients < 70kg or with unstable blood pressure Start at 500micrograms/hr (2.5mL/hr) initially and increase if possible. Continue for at least five days up to a max. of 14 days. (If surgical intervention is required during treatment continue for 5 days after surgery)

Nimodipine tablets 30mg For prophylactic use or to complete a course following iv administration: By mouth, 60mg every 4 hours starting within 4 days of haemorrhage and continuing for 21 days.


4th line anti-anginal medicines

Ivabradine (S) Cardiology only Affects heart rate but not blood pressure. Dose: initially 5mg twice daily (elderly patients 2.5mg twice daily) titrated after 3 -4 weeks to 7.5mg twice daily. Caution when used with beta-blockers or rate limiting calcium channel blockers.

Ranolazine (S) Consultant cardiologist only. Unlike other anti-anginals should not affect heart rate or blood pressure. Dose: Initially 375mg twice daily increased to 500mg twice daily after 2-4 weeks. May be increased if necessary after that to max 750mg twice daily.

Peripheral and Cerebral Vasodilators

Naftidrofuryl Capsules (s) Vascular surgeons only. Note: capsules must not be opened for patients with swallowing difficulties unless an N/G tube is in place. Contents have a strong local anaesthetic action and potentially can be aspirated. PVD dose: 100-200mg three times daily

Sympathomimetics These medicines should not be used outside the ITU / POCCU and CCU environments. Inotropic Sympathomimetics

Dobutamine infusion 2.5 - 10micrograms/kg/min adjusted according to response. Rarely up to 40micrograms/kg/min have been needed. Occasionally patients have responded to 0.5micrograms/kg/min. The dose should be gradually decreased rather than stopped abruptly. Concentrations less than 5mg/ml can be administered via a large peripheral line with monitoring for phlebitis

Infusion chart below


Infusion rate mL/hr for Dobutamine 500mg in 500mL (i.e. 1mg/ml) glucose 5% or sodium chloride 0.9%

Weight Micrograms/kg/min

2.5 5 7.5 10 12.5 15 17.5 20

40kg 6 12 18 24 30 36 42 48

50kg 7 15 22 30 37 45 52 60

60kg 9 18 27 36 45 54 63 72

50kg 10 21 31 42 52 63 73 84

80kg 12 24 36 48 60 72 84 96

90kg 13 27 40 54 67 81 94 108

100kg 15 30 45 60 75 90 105 120

110kg 16 33 49 66 82 99 115 132

Adrenaline (epinephrine) injection

Contact Anaesthetist for advice on use of adrenaline infusion as an inotropic agent.

Isoprenaline injection (s) Cardiologists and Anaesthetists only

Vasoconstrictor Sympathomimetics

Ephedrine injection (s) Anaesthetists only

Metaraminol injection (s) Anaesthetists only

Noradrenaline (s) (norepinephrine) injection

Anaesthetists only.

Phenylephrine (s) injection

Anaesthetists only.

Cardiopulmonary resuscitation Refer to Advanced Cardiac Life Support Guidelines issued by European Resuscitation Council and Resuscitation Council (UK).

Adrenaline (epinephrine) injection 1 in 10,000 (1mg/10mL).

Cardiac Arrest: 1mg (10mL) stat dose during resuscitation loop. Repeated every 3- 5mins if necessary during alternate cycles of CPR.


Anticoagulants and protamine

Prophylaxis of Venous Thromboembolism Prophylaxis of venous thromboembolism should be considered for all hospital in-patients. An assessment form should be completed for the notes and on ICE. Please see Hospital Policy on Prevention of Venous Thromboembolism (2010) for assessment criteria and recommended treatments. Available on the intranet under Policies and procedures/ General policies/ Trust clinical policies/ pharmacy/ Prevention of thromboembolism. For those patients already taking warfarin prior to a procedure Click here In case of difficulty, please contact the Haematology Department for advice regarding specific patients.


Treatment of Venous Thromboembolism

Treatment

Proven Deep Vein Thrombosis (DVT)

Pulmonary Embolism (PE)

Dalteparin

Warfarin

Contact Medicines Information (Ext. 2096) or the Haematology Department

IV heparin stat 5000units then

IV heparin or subcutaneous

Dalteparin

Warfarin


Guidelines for the Management of Pulmonary Embolism and Deep Vein Thrombosis Decision to Use Anticoagulants The potentially serious outcome associated with thromboembolic disease of the leg veins and lungs means that anticoagulant treatment with heparin should be started as soon as possible. Ideally, treatment with heparin should follow a robust clinical diagnosis, confirmed by a senior doctor of Registrar grade or above. However, if the suspicion of DVT or PE is high, heparin should not be withheld simply because a senior member of the medical staff is not immediately available. The diagnosis must be confirmed by imaging – compression ultrasound, isotope venography, ventilation – perfusion scanning or pulmonary angiography within 24 hours whenever possible. Subsequent therapy with warfarin should not be introduced until the clinical diagnosis is confirmed by an appropriate imaging study and pregnancy has been excluded. The principles of treatment with anticoagulants are outlined below, followed by more specific details of management. Patients with acute venous thrombosis and a history of current intravenous medicine use should be referred to the Lead Clinician for the Anticoagulant Service who will arrange an individual management plan. Principles of Treatment NOTE: Subcutaneous administration of heparins (unfractionated and Low Molecular Weight) should only be by injection into the abdomen or lateral part of the thigh. 1. Establish baseline full blood count, clotting screen and renal function. If age less

than 45 years, perform thrombophilia screen (before heparin therapy). 2. Arrange confirmatory imaging tests immediately, requesting urgent testing for results

within 24 hours. 3. For treatment of deep vein thrombosis, use subcutaneous low molecular weight

heparin (Dalteparin once daily). Monitoring is not required except in renal impairment. In such an event, liaise with Haematologists.

4. For treatment of pulmonary embolism, use intravenous, unfractionated Heparin or

subcutaneous once daily Dalteparin. Monitor intravenous unfractionated heparin treatment with APTT after 6 to 8

hours aiming for a therapeutic ratio of 1.8 - 3.3. This should be reached within 24 hours of commencing heparin.


Low molecular weight heparin does not require monitoring except in renal failure or the critical care situation. If the patient is haemodynamically compromised, consider emergency THROMBOLYTIC THERAPY providing there are no contra - indications. Fibrinolytics licenced for the treatment of PE are alteplase and streptokinase.

5. Initiate warfarin once diagnosis is confirmed by imaging. Monitor INR daily. Continue

warfarin, and discontinue heparin after at least five days and once INR is in the appropriate therapeutic range for 48 hours (whichever is the longer).

6. If on heparin for longer than 5 days, monitor platelet count daily against initial pre -

treatment result. Parenteral anticoagulants NOTE: Subcutaneous administration of heparins (Low Molecular Weight Heparins) should only be by injection into the abdomen or lateral part of the thigh. Heparins Low Molecular Weight Heparins Weight must be recorded on inpatient drug chart. Units should be written out in full not abbreviated to iu or u.

Haemoglobin, platelets and plasma sodium should be checked every 3 – 4 days for patients receiving low molecular weight heparins (LMWH). Renal function should be checked prior to dosing. NB. This should not delay treatment, if unavailable prior to 1st dose every effort should be made to ensure results available to guide dosing for subsequent doses.

Patients with impaired renal function receiving LMWH need their antifactor Xa levels to be monitored to ensure appropriate dosing (levels are taken 4 hours after the dose of dalteparin and testing is done on Mondays and Fridays). They are all administered by subcutaneous injection. Indication (for this hospital) Available as Dose

Dalteparin PE/ DVT treatment and prophylaxis

Ampoules/ pre-filled syringes

Click here and see VTE prophylaxis guidelines on the intranet.

Enoxaparin NSTEACS Pre-filled syringes See NSTEACS pathway Click here

For patients requiring immediate anticoagulation for AF, dalteparin given at a treatment dose of 200 units/kg once a day can be used.


Patients requiring long term anticoagulation with LMWH (i.e. not suitable for warfarin treatment) should be referred to haematology for advice on doses, monitoring and osteoporosis prevention. Only 2 weeks treatment will be supplied as discharge medication to ensure that the patient has some follow-up monitoring.

Patients requiring a long of prophylactic low molecular weight heparin e.g. after orthopaedic surgery, will be given the full course on discharge.

How to Use Low Molecular Weight Heparin (Dalteparin) for Treatment of Deep Vein Thrombosis Calculate total dose based on body weight according to the table below. The dose is 200 units/kg. The maximum daily dose is 18,000 units/day. Administer subcutaneously once daily in the trunk or thigh only.

In patients at high risk of bleeding, for example post surgery, 100 units/kg twice daily subcutaneously is recommended.

Note: The dose of Dalteparin is the same for the treatment of both deep vein thrombosis and pulmonary embolism.

1. APTT monitoring is not required. 2. Patients with renal impairment require special monitoring and may need

dosage reduction. Please contact Haematologists for advice about appropriate investigations (anti Xa levels).

3. Dalteparin should be continued for a minimum of 5 days and until the INR is in range for 2 consecutive days (whichever is the longer).

4. The dose should be written in both units and millilitres to provide a check on the dose for administration.

DVT treatment dosage with Dalteparin (based on 200 units per kg body weight)

Body weight (kg) units/daily Volume of pre - filled syringe

46 - 56 10,000 0.4ml

57 - 68 12,500 0.5ml

69 - 82 15,000 0.6ml

Over 83 18,000 0.72ml

How to Use Low Molecular Weight Heparin (Dalteparin) in the Treatment of Pulmonary Embolism 1. First give a loading dose of unfractionated heparin 5,000 units over 5 minutes

intravenously. 2. Calculate the total dose as for the treatment for deep vein thrombosis (table

above).


Other anticoagulants

Epoprostenol injection (s) Consultants only.

Taurolock injection (s) Consultant Nephrologists only

Unfractionated heparin Click here


Intravenous Unfractionated Heparin Continuous unfractionated heparin infusion is not used routinely but is an option for some patients particularly around the time of some surgery or if they have a high bleeding risk. How to Use Intravenous Unfractionated Heparin in Adults* 1. Establish baseline full blood count, clotting screen and renal function. 2. Give a bolus - loading dose of 5,000 units by intravenous injection. 3. Establish an infusion of heparin 1000units/mL (40mL containing 40,000units). Set

infusion to run at 1.3mL per hour (approximately 30,000 units over 24 hours). 4. Check APTT 6 to 8 hours after starting infusion. 5. Change the infusion rate to achieve the therapeutic APTT range of 1.8 to 3.3 by 24

hours (see table below).

For Adjusting the Dosage of Intravenous Heparin 1000 units/mL

APTT Ratio Infusion rate change

> 7.2 Stop for 60 minutes. At restart, reduce rate by 1mL/hr.

5.7 - 7.1 Reduce by 0.3mL/hr.

3.4 - 5.6 Reduce by 0.1mL/hr.

1.8 - 3.3 No change.

1.4 - 1.7 Increase by 0.2mL/hr.

< 1.4 Increase by 0.4mL/hr.

Repeat APTT ratio 6 - 8 hours after each alteration in rate, unless APTT ratio is > 7.2 when measurements should be made more frequently.

*Modified from Fennerty et al. British Medical Journal 1988; 297: 1285-8 6. Replace heparin infusion (syringe) at least every 24 hours and repeat APTT daily. 7. If heparin continues for more than 5 days, check platelet count daily. Once prescribed by the doctor, nurses with the relevant expanded role, training and following satisfactory assessment may administer the above according to guidelines set out by individual directorates within the Trust.


Management of Bleeding Due to Intravenous (Unfractionated) Heparin and Low Molecular Weight Heparin (Dalteparin): REMEMBER: - The Haematologist on - call is available for advice.

a) Intravenous (Unfractionated) Heparin

1. Stop heparin and send sample for APTT ratio. Because the half - life of heparin is short, stopping the infusion is usually sufficient.

2. If bleeding is severe/life threatening give protamine sulphate by slow

intravenous injection at a dose of 1mg for every 100 units heparin infused over the previous hour (maximum dose of protamine is 50mg). Following administration of protamine, repeat APTT ratio.

3. If bleeding continues after heparin has been stopped for 1 hour or despite giving

protamine, call Haematologist for advice.

b) Subcutaneous Low Molecular Weight Heparin (Dalteparin)

1. Check platelet count and send clotting sample to coagulation laboratory. 2. Consult haematologist regarding advice on management.

Note: Fresh frozen plasma is NOT helpful in the reversal of heparin overdose.

Oral Anticoagulants Warfarin is the first choice oral anticoagulant. However if patient is allergic or intolerant to warfarin then there are 2 other options available (acenocoumarol and phenindione). If either of these alternatives are to be prescribed please contact haematology/ Roald Dahl anticoagulation clinic for advice on starting doses and monitoring.


Warfarin Treatment Guidelines How to Start Warfarin Treatment* INR should be measured daily when initiating warfarin treatment. The INR is not accurate if the APTT ratio is > 5.0 A baseline INR should always be checked prior to initiation of warfarin. Inpatients should be loaded with warfarin as shown on the table below with an INR taken each day and the dose adjusted accordingly.

INR (in morning)

Warfarin dose (mg) (in evening)

Day 1. < 1.4 10

< 1.8 10

1.8 - 2.0 1

Day 2.

> 2.0 0

< 2.0 10

2.0 - 2.2 5

2.3 - 2.5 4

2.6 - 2.9 3

3.0 - 3.2 2

3.3 - 3.5 1

Day 3.

> 3.5 0

< 1.4 > 8

1.4 - 1.5 8

1.6 - 1.7 7

1.8 - 1.9 6

2.0 - 2.3 5

2.4 - 3.0 4

3.1 - 4.0 3

Day 4. Predicted maintenance dose. Predicted maintenance dose may be unreliable if patient has been given less than 10mg on days 1 or 2.

> 4.0 Omit dose until INR < 3

After day 4 Use clinical judgement

*Modified from Fennerty et al. BMJ 1988; 297: 1285 - 8

Outpatients are usually initiated on warfarin by giving an initial 3 day loading dose of 10mg, 10mg, 5mg or 10mg, 5mg, 5mg (depending on the size and age of the patient) with a compulsory INR check on the 4th day. (Where coumarin treatment has only been stopped temporarily in patients whose INR has been stable it is reasonable to reintroduce warfarin at the previous dose provided that other


medication has not changed significantly and there is no need for heparin cover whilst off warfarin). Note: Many medicines interact with warfarin, especially amiodarone, omeprazole, antibiotics, antiepileptics, NSAIDs and alcohol. Consult the BNF and/or Medicines Information (ext 2096) for a detailed list.

Recommended Target Ranges for INR

Recommended Therapeutic Range for Oral Anticoagulation

Condition Target INR (Range)

Prophylaxis/Treatment venous thrombosis

Treatment : pulmonary embolism

Prevention : systemic embolism

Atrial fibrillation

Valvular heart disease

Tissue heart valves

Post myocardial infarction (Includes aneurysm and dilatation)

Transient ischaemic attacks

2.5 (2.0 – 3.0)

Mechanical prosthetic valve

Anti - phospholipid syndrome

Recurrence of venous thromboembolism whilst on oral anticoagulation

3.5 (3.0 – 4.0)

Atrial fibrillation awaiting DC cardioversion 2.75 (2.2– 3.2)

Ref: Haemostasis and Thrombosis Task Force for the British Committee for Standards in Haematology. Guidelines on Oral Anticoagulation: Third Edition. Br J Haematol. (1998) 101:374,387 (The guidance for atrial fibrillation awaiting DC cardioversion is a hospital policy due to underanticoagulation causing delays in treatments) NB: Optimal range may require individual assessment according to clinical condition


Table: Recommended Duration of Oral Anticoagulant Therapy Short Term

Post - operative venous thrombosis in calf* 6 weeks

D - C cardioversion 8 weeks (4 weeks before; 4 weeks after)

Mural thrombus (post myocardial infarction) 12 weeks

Tissue valve prosthesis 12 weeks

Pulmonary embolism* 26 weeks (6 months)

Proximal deep venous thrombosis* 26 weeks (6 months)

*Recurrence whilst on therapy requires increased target INR. Recurrence after anticoagulant discontinued requires further therapy

Long Term

Recurrent venous thromboembolism

Vena caval filters

Anti - phospholipid syndrome

Cardiomyopathy

Mechanical valve prosthesis

Atrial fibrillation

Ref: Haemostasis and Thrombosis Task Force for the British Committee for Standards in Haematology. Guidelines on Oral Anticoagulation: Third Edition. Br J Haematol. (1998) 101:374,387

Management of Oral Anticoagulation in the Peri Operative Period Management depends upon the surgical risk of bleeding and the indication for anticoagulation Please see Hospital Policy Management of Oral Anticoagulation in the Peri Operative Period (requiring urgent surgery) for guidance and recommended treatment options. Available on the intranet under Policies and procedures/ General policies/ Division of Surgery/ Anaesthesia and Theatres


Management of over - anticoagulation With Warfarin/ other oral anticoagulants Note: Headache may be a symptom of haemorrhage 1. Life - threatening haemorrhage (including intra - cerebral bleeds)

Resuscitate as necessary. Stop warfarin. Send samples for INR, FBC, group and save plasma/cross match. Give vitamin K (phytomenadione - Konakion MM) at a dose of 5mg by slow IV

injection over 2 minutes. Alternatively vitamin K injection can be diluted in 50mL minibag of glucose 5% and run over 10 minutes.

Prothrombin complex concentrate is the product of choice in intracerebral haemorrhage – transfuse prothrombin complex concentrate 50 units/Kg or fresh frozen plasma 15ml/Kg.

Contact on - call Haematologist URGENTLY who will advise on the use of factor concentrates.

2. Less severe haemorrhage such as haematuria, epistaxis or headache

Withhold warfarin and check INR

Refer to Clinical Haematologist

If INR > 8 consider giving vitamin K (phytomenadione- Konakion MM) at a dose of 0.5 - 2mg by slow I.V. injection over 2 minutes. Alternatively vitamin K injection can be diluted in 50mL minibag of glucose 5% and run over 10 minutes.

Review after 48 hours.

3. High INR without haemorrhage or headache INR 4.5: Stop warfarin for 1 or 2 days then review after 24 hours.

INR 8 and other risk factors for bleeding are present: Stop warfarin for 1 to 2

days and add vitamin K (phytomenadione) 2.5mg orally as a single dose (Konakion MM Paediatric injection can be given orally).

4. Unexpected bleeding or headache at therapeutic levels of INR Cause of bleeding should be investigated as for patients who are not taking

warfarin.

Modify warfarin dose as appropriate.

If cerebral haemorrhage is suspected INR should be reversed to normal as soon as possible as in part 1 above.


Anticoagulant Clinic/ Long Term Anticoagulation There are clinics at both Royal Liverpool and Broadgreen hospitals. Patients are accepted only after the proper referral forms are fully completed and received by the clinic before the appointment dates. The decision to keep patients on long - term anticoagulant therapy should be reviewed regularly. The length of time for which the patient is anticoagulated is decided by the referring clinician, and not by the anticoagulant clinic. The Anticoagulant clinic must be informed of changes in the patient's clinical status and medicines and any planned procedures, so that the appropriate adjustment of anticoagulant therapy can be made. All patients taking warfarin should have an anticoagulant referral made when they are discharged. New patients will only be seen on Monday and Thursday clinics at Roald Dahl clinic in the Royal Liverpool Hospital. This should be taken into consideration when starting warfarin in both in patients and outpatients so that they can still have a day 4 INR check. Protamine sulphate

Protamine sulphate injection

10mg/ml (Click here)

Antiplatelet Medicines

Aspirin dispersible tablets

Prophylaxis of cerebrovascular disease or myocardial infarction: 75 - 300mg daily Low doses are also given post by - pass surgery.

-Aspirin e/c is considerably more expensive than the dispersible form with little evidence of any advantage. -Patients who are newly prescribed low - dose aspirin e/c will routinely have dispersible aspirin substituted by pharmacy. -Patients who are admitted on aspirin e/c will have this therapy continued.

The standard dose for low dose Aspirin is 75mg daily and doses of 150 - 300mg should be reviewed, with the following exception:

In the acute phase of ischaemic stroke where the dose should be 300mg daily for 14 days and then reduced to 75mg daily.


Clopidogrel tablets Dose: 75mg once daily Reserved for patients with aspirin hypersensitivity or true aspirin intolerance (contraindicated in active bleeding and little evidence of less adverse GI events over aspirin) Also used post stent insertion and for patients with high risk Acute Coronary Syndrome (ACS) as per RLBUHT management of patients with suspected ACS pathway available in A&E and HEC.

Dipyridamole tablets Consultants only. Only licensed for use as an adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves. Dose: 300 - 600mg in 3 - 4 divided doses before food.

Dipyridamole M/R capsules

Licensed for secondary prevention of ischaemic stroke and transient ischaemic attack, alone or in combination with aspirin (in addition to the above). To be commenced once aspirin has reduced to 75mg daily Dose: 200mg MR BD, preferably with food. Note: For patients with swallowing difficulties the capsules may be opened and the granules passed down a large bore N/G tube or swallowed in yoghurt/thickening agents.

Prasugrel tablets (s) Dose: 10mg daily (60mg loading dose) If under 60kg or in elderly patients 5mg daily. Only to be initiated in this trust prior to transfer to Liverpool Heart and Chest Hospital for Primary PCI in patients with STEMI- see ACS pathway in A&E and HEC. Patients may be admitted on this following PCI and if so it is to be continued.


Myocardial Infarction and fibrinolysis Primary Prevention of Myocardial Infarction Consult cardiovascular risk prediction tables in BNF (back pages) and hypertension section (click here) Secondary Prevention of Myocardial Infarction

All post - MI patients should be prescribed aspirin (loading dose of 300mg followed by 75mg daily indefinitely), provided there are no contra - indications.

Clopidogrel (300mg loading dose followed by 75mg daily) as an alternative to

aspirin should be reserved for those patients in whom aspirin is contra – indicated.

The use of clopidogrel in combination with aspirin is indicated for those

patients who have had a STEMI, NSTEMI or high risk Acute Coronary Syndrome as per suspected ACS guidelines. It is given for a fixed period depending on the indication which should be documented on the drug chart and on the discharge prescription

i) STEMI - 1 month clopidogrel ii) NSTEMI and high risk ACS- 12 months

All post - MI patients should be prescribed a beta – blocker and ACE inhibitor, provided there are no contra - indications.

i) Bisoprolol is the most usually prescribed betablocker post – MI ii) Ramipril is the most usually prescribed ACE inhibitor

All post - MI patients should be prescribed a statin initiated in hospital

regardless of initial total cholesterol level (if chol< 3.5 then decision for starting a statin should be made on an individual patient basis).

In this hospital patients post MI receive simvastatin 40mg daily or atorvastatin

80mg daily (if high risk). Atorvatatin 80mg daily should be reviewed at 6 months and this should be documented on the drug chart and discharge prescription. Click here for further guidance on statin treatment.

Calcium channel blockers should not be used routinely post - MI. However,

they may be suitable for patients without heart failure who have continuing angina, where beta - blockers are poorly tolerated or are contra - indicated. Only rate limiting calcium channel blockers such as diltiazem and verapamil have moderate evidence of decreasing mortality if used in place of beta-blockers.

The Joint British Societies’ guidelines on prevention of cardiovascular disease

in clinical practice (Dec 2005) recommend: 7) All patients should be prescribed a GTN spray as part of their discharge

medication in case of angina post-MI.


Guidelines for the Management of Patients with Acute Coronary Syndrome This trust has adopted the guidelines for management of non- ST elevation acute coronary syndrome produced by the Cheshire and Merseyside Cardiac and Stroke Network (CMCSN) and this has been incorporated into a pathway available in A&E and HEC. Please refer to this for further management. Acute Coronary Syndrome (ACS) covers a spectrum of conditions including: Unstable angina [UA] Non-ST segment elevation myocardial infarction [NSTEMI] Acute ST segment elevation myocardial infarction [STEMI] The term Non - ST Elevation Acute Coronary Syndrome (NSTEACS) is often used to cover both UA and NSTEMI. The treatment of NSTEACS is different from STEMI although there is a common patho-physiology and presentation. All STEMI patients should be considered for transfer to Liverpool Heart and Chest Hospital for Primary PCI instead of thrombolysis. They are given loading doses of antiplatelet medication prior to transfer (see pathway for details). Patients suspected of ACS should have a Troponin T level checked 6 hours after their chest pain started (or was most severe). RLBUHT now measures High sensitivity Troponin T and should be interpreted as below:

Interpret all HS Troponin T results in conjunction with clinical symptoms and ECG


Pharmacological treatments for suspected Acute Coronary Syndrome

Aspirin Administer as soon as NSTEACS suspected: 300mg stat dose to all patients, followed by 75mg daily. Exceptions are:

Patients with hypersensitivity to aspirin Aspirin intolerance due to previous GI

bleed Active or recent gastric ulcer Known significant aspirin - induced

dyspepsia despite gastroprotection. Patients with quiescent, old or operated peptic ulcer; mild dyspepsia; hiatus hernia or indigestion should receive aspirin.

Fondaparinux 2.5mg once daily subcutaneously For all NSTEACS patients if no contraindications and without high risk of bleeding as per ACS pathway. For patients with eGFR < 20ml/min use enoxaparin once daily instead.

Low molecular weight Heparin

Enoxaparin (Clexane®)

Used if fondaparinux contraindicated or patient requires full anticoagulation whilst being treated for ACS eg has a valve replacement, PE or DVT or has AF with high risk of cardiac thromboembolism. Enoxaparin 1mg/ kg twice daily subcutaneously for a minimum of 48 hours. (For renal patients with CrCl (eGFR)<30ml/min the dose is 1mg/kg once a day). Continue for 24 hours after patient is pain free or until revascularisation (if planned imminently).

Anti-thrombotic agents Patients already taking warfarin should have the need for anti-thrombotic medications discussed with senior medical staff

Clopidogrel Not all patients benefit from the addition of clopidogrel to aspirin. In view of this and the large cost of clopidogrel, it is only recommended:

Instead of aspirin for those NSTEACS truly sensitive to or intolerant of aspirin

In addition to aspirin for high risk patients (ACS risk score>6 as per pathway)

Dosage: 300mg initial dose followed by 75mg daily for either 1 month of STEMI and 12 months if NSTEACS.


Glycoprotein IIb / IIIa inhibitors

These medicines should be considered for all high risk NSTEACS patients with continuing or recurrent pain especially if are planned to undergo early PCI

Tirofiban is the product selected for use in this Trust. A protocol for administration is available for use on CCU and HEC.

Enoxaparin should be administered concomitantly with tirofiban

Prasugrel Administered as a single loading dose prior to transfer for primary PCI in STEMI patients (see pathway).

Nitrates Click here

Nitrates have no benefit with respect to event rate or mortality however can be used to relieve anginapain or prevent attacks of angina To relieve ischaemic pain/ angina administer Nitrates either IV; buccally or sub-lingually as appropriate. Oral nitrates can be used for patients continuing to have angina attacks despite current medications All patients should be prescribed sublingual GTN spray or tablets as an inpatient and on discharge.

Anti- ischaemic agents

Beta – adrenoreceptor blocking medicines Click here

Administer orally to relieve pain and ischaemia. They may improve prognosis therefore should be given to all patients without contra-indication. Usually bisoprolol is the beta-blocker of choice

post ACS. Contra – indications include:

1. Heart failure 2. Hypotension (systolic BP < 100 mmHg)3. Bradycardia ( < 60 beats per minute). 4. Asthma


Calcium channel blocking medicines Click here

Non rate limiting calcium channel blockers should be used in addition to beta – adrenoreceptor blocking medicines

If further angina or ischaemia occurs OR

If hypertension persists

Rate limiting calcium channel blockers should be used if beta-blockers are contraindicated (i.e.

Diltiazem) providing : There is no clinical heart failure No likelihood of significant left ventricular

impairment (check ECHO) Initial heart rate is >= 60 bpm. There is no hypotension (systolic BP < 100

mmHg)

Potassium channel openers

Nicorandil 20mg twice daily has been shown to significantly reduce transient ischaemia, SVT and VT compared to placebo when added to standard therapy Can be added to nitrates, beta – adrenoreceptor blockers and calcium channel blockers if there is recurrent ischaemia or angina (unstable angina is an unlicensed indication)

Statins Click here

There is evidence that intensive treatment with statins may have benefits in ACS therefore atorvastatin 80mg daily should be prescribed for patients with high risk ACS otherwise simvastatin 40mg at night is recommended.

Other medicines post ACS

Angiotensin converting enzyme inhibitors Click here

They are of proven benefit post myocardial Infarction especially where the infarction is large, anterior or has resulted in moderate to severe left ventricular dysfunction or heartfailure. However due to evidence of benefit as secondary prevention they are recommended for all NSTEACS patients if not contra-indicated.


Fibrinolytic Medicines. These medicines may be used for patients with a diagnosis of ST elevation MI although Primary PCI is now first line treatment. See pathway available in A&E, HEC & CCU. Alteplase is also licensed for the treatment of life threatening Pulmonary Embolism and these are available in the Emergency Medicines Store and A&E majors.

Tenecteplase Injection For acute myocardial infarction if not suitable for Primary PCI as per ACS pathway - see product information for dosing. It should not be administered via a line containing dextrose

Alteplase injection For life threatening pulmonary embolism- see product information for dosing Used in stroke patients only if recommended by stroke specialist nurse or consultant as per pathway during working hours.


Management of side effects of thrombolytic therapy Arryhthmia Common side-effect. Specific treatment rarely needed unless pulseless VT or VF. Check plasma potassium and correct if less than 4.0 mmol/L

Other Fibrinolytic Medicines

Urokinase Injection (s) Radiologists and Consultants only. Unlicensed medicinal product in the UK. Used in this trust for unblocking the lumens of central lines – please speak to the specialist iv access nurse before urokinase is prescribed.

Antifibrinolytic Medicines and Haemostatics Aprotinin injection (s) Anaesthetists only

Tranexamic acid tablets/injection

By mouth, 1 - 1.5g 2 - 4 times daily. By slow i.v. injection, 0.5 - 1g 3 times daily.

Drotecogin alfa injection (recombinant activated protein C)

(s) ITU only

Lipid - regulating Medicines Secondary causes of hyperlipidaemia include hypothyroidism, poorly controlled diabetes, obesity, excessive alcohol intake, beta - blockers, thiazide diuretics or oestrogens. Correction of secondary causes and/or dietary measures may be sufficient to reduce levels.

HMG Co - A Reductase Inhibitors ('Statins') All patients prescribed a statin should have baseline liver function tests checked. Patients are also advised to report any unexplained muscle pain or weakness, since statins are associated with myalgia, myositis and myopathy. Note: Discontinue if myopathy diagnosed. Statins should also be discontinued in active liver disease or if there is unexplained persistent elevation of serum transaminases The hospital has adopted the Cheshire and Merseyside Cardiac Network guidelines for statins which is the same as the current NICE recommendations (CG67 lipid modification March 2010).


Statins for primary prevention Statin therapy is recommended as part of the management strategy for the primary prevention of CVD for adults who have a 20% or greater 10-year risk of developing CVD (see charts at the back of the BNF). If the decision is taken to start a statin after discussion about risks and benefits with the patient then simvastatin 40mg at night should be prescribed. There are no specific lipid targets for primary prevention. Statins for secondary prevention All patients who require a statin for secondary prevention should have a baseline lipid level checked (although for ACS patients there is no need to wait for the result before starting a statin). Patients should be started on a statin of low acquisition cost (simvastatin 40mg at night) and then lipid levels monitored and the dose titrated (maximum 80mg at night) to reach target cholesterol levels (total chol <4mmol/L and LDL chol <2mmol/L).

Simvastatin tablets Usual starting dose range 20-40mg at night. If cholesterol targets not achieved after 6 weeks consider increasing dose up to maximum 80mg at night. Caution in using high dose simvastatin in renal patients and those on interacting medications which can increase risk of myopathy and myositis (see BNF for interactions). Maximum dose 20mg at night if patient is on concomitant amiodarone or verapamil.

Atorvastatin tablets Reserved for use in this trust as the high potency statin for patients with high risk Acute Coronary Syndrome Dose: 80mg once daily Lower doses (ie 10 and 20mg daily) should not be used for secondary prevention unless patient has a contraindication to simvastatin.

Rosuvastatin tablets (s) Lipid clinics only

Important interactions involving "statins"

Simvastatin may enhance the effect of warfarin. Other lipid – lowering medicines, macrolide antibiotics (erythromycin and

clarithromycin), and ciclosporin may increase the risk of myositis with “statins”. Patients taking simvastatin should have their treatment withheld for the duration of macrolide antibiotic treatment.

Imidazole antifungal medicines (effect of “statins” may be enhanced) Maximum dose 20mg at night if patient is on concomitant amiodarone or

verapamil.


Anion - exchange Resins Due to poor compliance and tolerance these are generally now only used as add on therapy for resistant hyperlipidaemia.

Colestyramine Light sachets

8 - 24g daily in water in single or up to 4 divided doses. Other medicines should be taken at least 1 hour before or 4 – 6 hours after colestyramine to reduce possible interference with absorption.

Ezetimibe (inhibits absorption of cholesterol) (s)

Consultant use only

Fibrates Note: All fibrates can cause a myositis - like syndrome, especially in patients with impaired renal function and when used in combination with statins

Fenofibrate tablets (s) (micronised)

Consultants only

Nicotinic Acid group

Niaspan (s) Consultants only

Fish oils

Omega–3–acid ethyl esters capsules (Omacor ®) (s)

Consultant Cardiologists only following Cheshire and Merseyside Cardiac and Stroke Network guidelines. Secondary prevention following myocardial infarction. Dose: 1 capsule (1g) daily with food

Local Sclerosants

Ethanolamine injection(s) Surgeons only.

Sodium tetradecyl (s) sulphate injection

Surgeons only. Note: also known as STD injection


RESPIRATORY SYSTEM Contents (Click on heading to go to that section) Management of Chronic Persistent Asthma in Adults

Asthma management - general notes Management of an Acute Asthmatic Attack Notes for Asthma Management during Recovery in Hospital Nebulisation Guidelines

Special Considerations Nebulisation Volume Driving Gas Flow Rate Care of the Nebuliser Chamber Use of Nebulisers in Chronic Disease Peak Flow Meters Solutions for Nebulisation

Bronchodilators Adrenoreceptor agonists Long Acting Beta2 agonists Antimuscarinic bronchodilators Theophylline

Inhaled Corticosteroids (ICS)

Compound bronchodilator preparations Antihistamines, hyposensitisation and allergic emergencies

Antihistamines Respiratory stimulants Oxygen therapy

Mucolytics Cough preparations Systemic nasal decongestants


Management of Chronic Persistent Asthma in Adults

(Based on BTS/SIGN Guideline on Management of Asthma 2008, updated 2009)

The inhaled corticosteroid doses given below refer to beclometasone (BDP) given via CFC-MDI. Dose adjustments have to be made for some CFC-free aerosols, other devices and other corticosteroid molecules. If unsure please check with pharmacy.

STEP SYMPTOMS/PROBLEMS MANAGEMENT

1 Infrequent symptoms. Normal lung function

Salbutamol or other short acting beta2 - agonist inhaled `as required'.

2 Short acting beta2 - agonist used ≥ 3 times/week OR

Night time symptoms 1/week OR

Exacerbation in past 2 years OR

Symptomatic ≥ 3 times/week

Add inhaled corticosteroid (ICS) e.g. beclometasone proprionate (BDP) 100 - 400mcg b.d. or equivalent. Start at steroid dose appropriate to disease severity. An appropriate starting dose for many patients is 200 mcg bd (BDP or equivalent)

If still poorly controlled As above PLUS

Long acting beta2 – agonist (LABA) e.g. salmeterol 50 mcg b.d.

If no response Stop LABA increase dose of ICS to upper end of dose

range (up to 400 mcg b.d BDP or equivalent)

3

If control still poor Continue LABA Increase dose of ICS up to 400 mcg b.d.

(BDP or equivalent)

4 If patient remains poorly controlled All of the above PLUS 6 weeks sequential therapeutic trial of one or more of:

Increase ICS up to 1000 mcg b.d. BDP or equivalent

Leukotriene antagonist. Theophylline MR preparation Salbutamol MR .

5 Still not controlled Refer to Chest Physician.

Note : Always check compliance and inhaler technique before moving up a step

In asthma treatment, long acting beta 2 agonists should NEVER be used without

concomitant ICS.


Combination inhalers in asthma- The SMART regime In selected adult patients at step 3 who are poorly controlled or in selected adult patients at step 2 (above BDP 400mcg/day who are poorly controlled) the use of budesonide/formoterol in a single inhaler as rescue medication instead of a short acting beta-2 agonist, in addition to its regular use as controller therapy has been shown to be an effective treatment regimen. Patients taking rescue budesonide/formoterol once a day or more should have their treatment reviewed. Careful education of patients about the specific issues around this management strategy is required and any patient who is thought to be suitable must be reviewed and assessed by the asthma specialist nurse.

Asthma management - general notes

START at step most appropriate to initial severity.

RESCUE COURSE of oral prednisolone can be given at any step.

Give 30 - 40mg daily in the morning (up to 60mg if already on oral steroids) for 3 - 7 days.

The following guidelines may be followed when stopping a course of oral

corticosteroid: Abrupt withdrawal is appropriate if the course of systemic corticosteroid has

continued for up to 3 weeks at a dose of up to 40mg daily.

Doses of systemic corticosteroids should be reduced gradually in all patients who have:

o had courses lasting more than 3 weeks. o had courses lasting 3 weeks or less AND

have received repeated courses of a systemic corticosteroid OR received a short course of a systemic corticosteroid within one

year of cessation of long - term therapy OR may have other reasons for adrenocortical insufficiency OR have repeatedly taken doses of corticosteroid in the evening

REVIEW regularly. STEP DOWN treatment in well controlled patients who have been stabilised

for at least three months, (decrease inhaled corticosteroid dose by 25 – 50%).

TERBUTALINE may be preferable for patients who experience tremor with salbutamol.

THEOPHYLLINE preparations should ALWAYS be prescribed by BRAND name due

to the differing release characteristics between preparations.

CHECK inhaler technique. Refer to Asthma Nurse or your ward pharmacist if necessary.

PEAK FLOW METER should be prescribed if patient is not already using one and

advice given regarding response to changes in PEFR and symptoms.


Management of an Acute Asthmatic Attack

(Based on British Thoracic Society / SIGN Guidelines 2008, updated 2009)

SIGNS/SYMPTOMS MANAGEMENT

Uncontrolled asthma: Speech normal Pulse < 110 beats/min

Respiratory rate < 25 breaths/min

Peak flow > 50 - 75% of predicted or best

Record PEFR Nebulised salbutamol 5mg or multiple

actuations (15 - 20) of metered dose inhaler via large volume spacer. Monitor response after 15 - 30 mins.

If PEFR 50 - 75% of normal start oral prednisolone 30 - 60mg and step up usual treatment.

If PEFR > 75% of normal step up usual treatment.

Acute severe asthma: Cannot complete sentences. HR ≥ 110 beats/min. Respiratory rate > 25 breaths/min. Peak flow 33-50% of predicted or best.

Oxygen 40 - 60% (aim SpO2 94-98%) Nebulised salbutamol 5mg 4 - 6 hourly

using oxygen as the driving gas. If poor response, give nebulised ipratropium

500 micrograms 6 hourly using oxygen as driving gas

Prednisolone 30 - 60mg stat. and daily in the morning or Hydrocortisone 100mg i.v. stat. and q.d.s. if oral route is not available.

Magnesium sulphate IV 1.2-2g in 100ml 0.9% sodium chloride over 20 minutes

Monitor response after 15 - 30 mins.

Life threatening asthma: Silent chest Drowsiness Hypotension Cyanosis Arrhythmia Exhaustion SpO2 < 92% PaO2 <8 kPa Peak flow < 33% of predicted/ best

Discuss with senior clinician / ITU

Oral prednisolone / IV hydrocortisone as above

Continuous oxygen as above Nebulised salbutamol 5mg every 15 – 30

minutes and ipratropium bromide 500microgram 6 hourly driven by oxygen

Magnesium sulphate IV 1.2 – 2g in 100ml 0.9% sodium chloride over 20 minutes.

Aminophylline 5mg/kg (250 - 500mg) i.v. in 250 ml glucose 5% or sodium chloride 0.9% over 20mins (omit if already taking oral theophylline and check level) Followed by 0.5mg/kg/hr adjusted according to plasma theophylline conc. OR

salbutamol 250microgram i.v. in glucose 5% over10 mins,then 3 - 20microgram/min according to response and heart rate. See infusion table further in chapter.


Notes for Asthma Management During Recovery in Hospital

Patients should be managed, where possible, in specialist rather than general wards

Inhaled corticosteroids (ICS) should not be stopped on admission. For patients previously on inhaled steroids, the dose should be stepped up.

ICS and oral steroids should be administered concomitantly in the acute phase Standard inhalers should replace nebulisers 24 - 48 hours before discharge.

Change over should not take place until PEFR is at least 75% of the predicted value.

Check inhaler technique and change inhaler device if appropriate. Oral steroids may be discontinued prior to discharge, if appropriate.

Alternatively a short course may be prescribed to complete at home- a definite course length should be specified.

All patients admitted with an asthma exacerbation should be referred to the asthma specialist nurse for review whilst an inpatient.

On discharge, patients should be followed up by clinicians with expertise in asthma management, preferably within 30 days of discharge.

Nebulisation Guidelines The main indications for the use of a nebuliser are:

To deliver salbutamol or ipratropium to a patient with an acute exacerbation of asthma or airways obstruction i.e. the patient is too ill or unable to use hand held inhalers.

To deliver salbutamol or ipratropium on a regular basis to a patient with asthma or airways obstruction who has been shown to benefit from regular treatment with higher doses.

To deliver prophylactic treatment e.g. a corticosteroid or antibiotics, to a patient unable to use other inhalation devices.

Special Considerations Nebulised steroids should only be initiated on the advice of a consultant chest physician. A special nebuliser with a mouthpiece instead of a face mask is recommended to minimise the incidence of side effects and produce the optimal droplet size. Contact the Asthma Nurse for details. If ipratropium bromide is being nebulised for any length of time, a mouth piece nebuliser should be used. This is to reduce the incidence of conjunctival irritation or precipitation of glaucoma in susceptible individuals. If this is a particular problem the patient should wear glasses or be advised to close their eyes for the duration of nebulisation. Alternatively, contact the Asthma Nurse for further advice.


Nebulisation Volume The recommended volume for the nebuliser chamber is 2mL. This is because there is a fixed residual volume left in the nebuliser. This may account for as much as 20% of the dose if nebulisation volumes are too small. Different makes of nebuliser chamber require different fill volumes for optimal medicine delivery. If the volume of the medicine(s) to be nebulised is < 2ml, dilute to 2ml using sodium chloride 0.9%. This will give a nebulisation time of approximately 3 - 4 mins. Driving Gas Oxygen* should be the driving gas in asthmatic patients. For patients who have COPD AND evidence of carbon dioxide retention, air should be the driving gas. (NOTE this is not true for all COPD patients) Flow Rate A flow rate of 6L - 8L/minute will deliver the correct size of droplet required for medicine penetration into distal airway. Care of the Nebuliser Chamber The nebuliser should be rinsed daily with sterile water, wiped dry with a paper towel and the inner tube cleaned using compressed air or oxygen. Cleaning is important in order to reduce the risk of bacterial contamination and prevent the build up of crystallised medicine in the nebuliser. The nebuliser should be replaced every 3 to 4 days. It should also be replaced if the medicine(s) crystallise or if the nebuliser fails to function. Use of Nebulisers in Chronic Disease Before prescribing nebulisers for patients at home, the patient should be referred to the respiratory team for a nebuliser trial. If a nebuliser is prescribed for home use, patients should be instructed not to treat acute attacks at home without seeking medical assistance and they must be given clear instructions on the use of the nebuliser e.g. method and frequency of use; servicing etc. Instructions on peak flow monitoring and action to take in the event of worsening asthma should also be given. Peak Flow Meters A pre and post nebulisation peak flow should be taken for all asthmatic patients. The post nebulisation peak flow should be taken 20 - 30 minutes after nebulisation. This is especially important if ipratropium bromide is being nebulised as it takes at least 30 - 40 minutes for this medicine to produce maximal bronchodilation. The patient should preferably be standing when a PEFR measurement is taken. If the patient is unable to stand they should be in an upright sitting position. When PEFR is > = 75% of the predicted value, nebulised bronchodilators can usually be stopped and replaced by conventional hand held inhalers, (via a large volume spacer if appropriate).


Solutions for Nebulisation

MEDICINE/ STRENGTH DOSE COMMENTS

Bronchodilators Salbutamol 2.5mg/2.5mL 5mg/2.5mL

2.5 – 5mg 4 - 6 hourly

5mg dose can cause tachycardia and/or tremor in some patients which can be resolved by using the 2.5mg dose.

Terbutaline Respules 5mg/2mL

5 - 10mg 4 - 6 hourly

Only used in patients intolerant of salbutamol

Ipratropium bromide 250microgram/mL

250 - 500 microgram 6 hourly

Can be mixed with salbutamol or terbutaline. Click here if eye irritation is a problem.

Mucolytics Sodium chloride 0.9%

5mL 6 hourly Used to loosen secretions

Sodium chloride 6% 4mL Can be used just as a stat. dose prior to physiotherapy for induction of sputum for samples. Or used regularly to loosen secretions after sodium chloride 0.9% has failed.

Corticosteroids Budesonide 0.5mg/2mL 1mg/2mL Fluticasone 0.5mg/2ml 2mg/2ml

1 - 2mg b.d. 0.5-2mg b.d

Nebulise bronchodilators first. A special nebuliser is recommended to give optimum particle size. Contact the Asthma Nurse for details. Fluticasone is twice the potency of budesonide

therefore doses are not equivalent.

Notes:

Bronchodilators should be nebulised before physiotherapy to optimise the clearance of bronchial secretions.

If more than one medicine is to be nebulised, bronchodilators should be nebulised separately first.

If antibiotics are to be nebulised, contact Medicines Information (ext 2096) or asthma nurse for advice if necessary.


Bronchodilators Adrenoreceptor agonists

Selective beta2 agonists Various inhaler devices are available. Ask your ward pharmacist or the Asthma Nurse for details.

Salbutamol inhaler/nebuliser solution /SR tablets/syrup/injection

Inhalation: Aerosol dose, 100 - 200 micrograms (1 - 2 puffs) ‘when required’ in asthma, or 3 to 4 times daily in COPD. Dry powder dose, Ventodisks; 200 - 400 micrograms. Accuhaler; 200micrograms (one blister) Nebulisation, 2.5 - 5mg 6 hourly (acute asthma attack up toevery 15 - 30 minutes). In severe exacerbations 2-4 hourly initially then reduce frequency on review. By mouth, SR tablets, 4 - 8mg twice daily. Syrup, 4mg 3 - 4 times daily. By s.c. or i.m. injection, 500 micrograms (8 micrograms / Kg), repeated every 4 hours if necessary. NB this route/method is rarely used. By slow i.v. injection, 250 micrograms (4microgram/kg) repeated if necessary. To be injected slowly. The injection can be diluted with water for injection to facilitate administration. By i.v. infusion, 5 microgram/min adjusted according to response and heart rate. See infusion table on next page. Usually in range 3 - 20 micrograms/minute. (In patients with respiratory failure, higher doses have been used successfully) Recommended dilution: 5mg in 500ml of sodium chloride 0.9% or glucose 5% (i.e. concentration 10micrograms / ml)

Salbutamol infusion rates for 5mg in 500ml infusion

Dose (micrograms / min ) Rate (ml / hour)

3 18

5 30

7.5 45


Salbutamol infusion rates for 5mg in 500ml infusion

10 60

15 90

20 120

30 180

45 270

Terbutaline inhaler/ respules/injection/ syrup

Terbutaline preparations may be considered if a patient experiences severe tremor with salbutamol. There is a Trust policy and prescribing guidelines document covering the Continuous Sub-cutaneous Infusion of Terbutaline (CSIT) using a portable syringe driver. The document details assessment procedures, pump setup and maintenance doses. The Asthma Nurse Specialists should be contacted for a copy of the document.

Theophylline Theophylline is a narrow therapeutic index drug and TDM must be carried whilst on therapy (especially IV therapy) Check with pharmacy/BNF for drug interactions and patient factors which may affect theophylline metabolism. Oral theophylline/aminophylline For chronic long term management of asthma and COPD

Theophylline SR tablets Uniphyllin

All theophylline preparations should be prescribed by brand name due to the differing bioavailability of SR preparations. The preferred brand for initiation of therapy is Uniphyllin. Dose: starting dose, 200mg every 12 hours adjusted according to blood levels and response.

Aminophylline SR tablets (Phyllocontin)

Dose: starting dose, 225mg every 12 hours adjusted according to blood levels and response.

IV aminophylline For deteriorating acute severe asthma / severe acute exacerbation of COPD / respiratory failure.


Loading dose (If patient is usually on oral theophylline, omit loading dose) By IV infusion: 5mg/kg (usually 250 - 500mg) IV in 250ml sodium chloride 0.9% or glucose 5% over at least 20-30 mins

Maintenance dose By continuous IV infusion : 0.5mg / kg / hr, (if the patient is obese use IBW) The rate can then be adjusted according to plasma theophylline concentration

Target plasma concentration: 10-20mg/ L Plasma concentration should usually be checked within 12 hours of initiating IV maintenance infusion and the infusion rate adjusted accordingly, if necessary..

Infusion fluids & dilution: 1000mg in 1L of sodium chloride 0.9% (most stable) or glucose 5% or glucose 4% in sodium chloride 0.18%

Aminophylline infusion rates for dosage 0.5mg / Kg /hr of a 1mg / ml infusion

Body weight (Kg) 40 50 60 70 80 90

Rate (ml / Hr) 20 25 30 35 40 45

Long Acting Beta2 agonists (LABA’s) Asthmatic patients requiring long term regular bronchodilator therapy MUST also be receiving regular and adequate doses of inhaled corticosteroids (ICS) These agents should not be used for the relief of an acute attack and should be added to existing corticosteroid therapy – not replace it.

Salmeterol inhaler (Evohaler or Accuhaler)

Dose, Asthma and COPD 50 micrograms twice daily

Note Salmeterol Evohaler is 25mcg/puff hence dose is 2 puffs twice daily Salmeterol Accuhaler is 50mcg/ puff hence dose is 1 puff twice daily

Formoterol 6microgram turbohaler Formoterol 12microgram turbohaler

Dose, Asthma 12 micrograms twice daily increased to 24mcg twice daily in severe disease. For short term symptomatic relief (not acute asthma) additional doses can be taken to max. 72mcg daily (max. single dose 36mcg) COPD 12 micrograms twice daily


Antimuscarinic bronchodilators

Ipratropium bromide inhaler /nebuliser solution Tiotropium Handihaler and 18mcg inhalation capsule Respimat aerosol inhaler device 2.5mcg/inhalation

Aerosol Dose, COPD 2 puffs (40 micrograms) 4 times daily

Nebulisation Dose, 250 - 500 micrograms 4 times daily

Current national guidelines do not recommend routine use of ipratropium for chronic asthma management (use in acute setting only) This should be borne in mind when converting patients from nebulisers to inhalers after an acute episode.

For COPD ONLY

Handihaler device dose 18mcg inhaled once daily

Respimat device dose 5mcg (2 puffs) inhaled once daily

Inhaled Corticosteroids (ICS) It is recommended that all patients prescribed inhaled corticosteroids (ICS) via an MDI device should use a spacer device to increase airway deposition and reduce oropharyngeal deposition, which predisposes the patient to a sore mouth, hoarse voice and oral candidiasis. Patients should also be advised to rinse their mouth out after using their corticosteroid inhaler. Beclometasone, budesonide and fluticasone would appear to be equally

effective in the recommended doses. Fluticasone is twice the potency of CFC - containing beclometasone and

budesonide. QVAR doses are not equivalent to CFC- containing beclometasone doses. QVAR 100 micrograms is approximately equivalent to 200micrograms

beclometasone. QVAR should always be prescribed by brand name.

All ICS doses stated below are licensed only for use in asthma. No ICS, as a single agent, is licensed for use in COPD

ICS in Asthma

QVAR MDI, easibreathe or autohaler device

Dose: 50 - 400 micrograms twice daily depending on asthma severity.

Budesonide Turbohaler or easyhaler device

Dose: 200-800mcg twice daily depending asthma severity.


Fluticasone MDI, Accuhaler or easyhaler devices

Dose: 125-500mcg twice daily. Increased to max. 1mg twice daily, according to asthma severity.

ICS in COPD Please note the only licensed ICS option in COPD is the combination of ICS WITH LABA (i.e. Seretide 500 accuhaler or Symbicort 400/12 turbohaler, see next page for details) NICE 2010: In people with stable COPD who remain breathless or have exacerbations despite use of short-acting bronchodilators as required, offer the following as maintenance therapy: if forced expiratory volume in 1 second (FEV1) ≥ 50% predicted: either long-acting

beta 2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) * NOT FOR ICS YET *

if FEV1 < 50% predicted: either LABA with an inhaled corticosteroid (ICS) in a combination inhaler, or LAMA.

Offer LAMA in addition to LABA + ICS combination to people with COPD who remain breathless or have exacerbations despite taking LABA + ICS, irrespective of their FEV1.

Compound Corticosteroid Preparations Compound ICS and long acting bronchodilator inhalers have not been found to be significantly more effective nor safer than the separate constituents used together and stepping up/ down ICS doses in asthma is difficult with the compound inhalers. However a compound device may help to improve compliance, decrease inhaler burden and reduce the number of prescription charges payable especially when doses will remain stable. They are also the only licensed ICS option in COPD management. Be aware that the strength of salmeterol per puff in the two Seretide device differs. Accuhaler 50micrograms/ puff Evohaler 25micrograms/ puff

Seretide Accuhaler 100/50 Accuhaler 250/50 Accuhaler 500/50 Accuhaler *** FORMULARY CHOICE

Available as 100, 250 and 500 mcg (fluticasone strength). Each product contains 50 micrograms of salmeterol. Asthma dose, 1 puff twice daily (all strengths) COPD dose, 1 puff twice daily (only 500mcg strength licensed)


Symbicort Turbohaler 100/6 turbohaler 200/6 turbohaler 400/12 turbohaler *** FORMULARY CHOICE

Available as 100, 200 and 400 micrograms inhalers (budesonide strength) 100 and 200 preparation contains 6 microgram formoterol per puff 400 preparation contains 12 micrograms formoterol per puff Asthma dose 100/6 and 200/6 strength, 1 – 2 puffs twice daily. Max 4 puffs twice daily. 400/12 strength, 1 puff twice daily. Max 2 puffs twice daily. If asthma is well controlled the dose can be decreased to the lowest effective dose given once daily. COPD dose 400/12 strength 1 puff twice daily

Seretide Evohaler 50/25 Evohaler 125/25 Evohaler 250/25 Evohaler *** NON FORMULARY

CHOICE ONLY TO BE USED IF OTHER

DEVICES UNSUITABLE

Only licensed for use in asthma Available as 50, 125 and 250 mcg (fluticasone strength). Each product contains 25 micrograms of salmeterol. Asthma dose, 1 – 2 puffs twice daily (all strengths) This device is not licensed in COPD- use accuhaler or symbicort turbohaler as above.


Algorithm for appropriate inhaler choice This algorithm aims to give a guide to inhaler choice when testing inhaler technique. Patient choice is an important factor when ensuring compliance. However, where possible, the algorithm should be used to ensure the cost effective use of the available inhaler devices.

DexterityProblem ?

Inability to use:1.Easibreathe2.Turbohaler3.Autohaler

?

Is spacer acceptable ?

STANDARDINHALER &

VOLUMATICOR

AEROCHAMBER

Propellant/Taste problems

?

AUTOHALER

N Y

Y

ACCUHALER

N

TURBOHALEROR

ACCUHALER If the lactose

taste is needed for

acknowledge -ment

of dose

N

Y

N

Technique problems?1 Does patient need”Click” prompt

AND/OR2.Does patient actuate

Easibreathe® prematurely ?

EASIBREATHE

N

Y

Y

Poor Co-ordination

?

Poor Inspiration ?

N

Y Y

From this point onwards please consider seeking

advice from Your ward pharmacist or asthma nurse specialist


Antihistamines Sedating Antihistamines

chlorphenamine [chlorpheniramine] tablets/syrup/injection

Choice in pregnancy and porphyria. Symptomatic relief of pruritus and other allergy: By mouth, 4mg every 4 - 6 hours. Parenteral, emergency treatment of anaphylactic reactions by slow i.v. injection, 10 - 20mg diluted with 5 - 10ml sodium chloride 0.9%and given over 1 minute.

Hydroxyzine tablets

Pruritus: Initially 25mg at night increased if necessary to 25mg 3 - 4 times daily.

Non - sedating Antihistamines

Cetirizine tablets

Recommended preparation 10mg daily.

Fexofenadine tablets

Symptomatic relief of seasonal allergic rhinitis Dose: 120mg once daily

Symptomatic relief of chronic idiopathic urticaria Dose: 180mg once daily

Respiratory stimulants For use in patients with hypercapnic respiratory failure who are becoming drowsy / comatose and in whom ventilatory support is contra – indicated or not immediately available.

Doxapram infusion By infusion: See infusion table below Frequent arterial blood gas and pH measurements are necessary during treatment to ensure appropriate dosage.

Doxapram Intravenous infusion for acute respiratory failure

Time from start of infusion Dose Doxapram 2mg/mL in glucose 5% infusion

0 - 15 mins 4mg/min 120mL/hr for 15 mins



60 mins onwards 1.5mg/min 45mL/hr continuously


Oxygen therapy There is a trust oxygen policy and prescription chart which must be followed for oxygen prescribing and administration within the trust. Please refer to this document which is available via the intranet. Mucolytics Oral mucolytics are recommended by the NICE guideline for COPD management (2004) to trial in those patients who suffer with a chronic productive cough. A four week trial should be given and the patient then reviewed to assess benefit. If no benefit is gained the mucolytic should be discontinued. They are also recommended in bronchiectasis.

Carbocisteine 375mg capsules 250mg/5ml syrup

Dose, initially 750 mg three times daily for 4 weeks and then review response. If no improvement, discontinue treatment. If noticeable improvement, continue on maintenance dose of 750mg twice daily thereafter.

Nebulised mucolytics are given to patients having difficulty in expectorating sputum. Bronchiectasis patients may be on these long term at home.

Sodium chloride 0.9% For nebulisation Dose, 5ml as required (usually QDS)

Sodium chloride 6% For nebulisation. Dose, 4ml as required (usually QDS) If used for prolonged periods a mouthpiece may be desirable due to irritation to the eyes.

Cough preparations

Cough suppressant Pholcodeine

linctus(5mg/5mL)

Dose, 5 - 10mL 3 - 4 times daily when required. May be diluted in warm water and sipped. (sugar free linctus also available)

Demulcent Simple linctus

Dose, 5mL 3 - 4 times daily when required.


Systemic nasal decongestants

Pseudoephedrine tablets/syrup

Dose, 60mg 3 times daily for short term use only. Avoid use in patients with hypertension, hyperthyroidism, coronary heart disease or diabetes.


CENTRAL NERVOUS SYSTEM Contents (Click on heading to go to that section) Benzodiazepine Policy

CSM advice Initiating Therapy Alternative Strategies On Discharge Patients on Long Term Therapy

Hypnotics and anxiolytics

Hypnotics Anxiolytics

Medicines Used in Psychoses and Related Disorders

Antipsychotic medicines Antipsychotic Depot Injections Antimanic medicines Antidepressant Medicines

Tricyclic and related antidepressant medicines Selective Serotonin Re - Uptake Inhibitors

Medicines used in the treatment of obesity Medicines Used in Nausea and Vomiting

Guidelines for Chemotherapy - induced Nausea and Vomiting Choice of Anti - emetic For Regimens of Low, Moderate and High Risk of Emesis Assessing the Emetogenicity of a Regimen Risk of Emesis with Single or Combination Cytotoxic Regimens Guidelines for the Management of Post Operative Nausea & Vomiting

Analgesics

Management of Acute Pain Non-opioid analgesics Opioid analgesics Equivalent Doses of Opioid Analgesics Neuropathic pain Antimigraine Medicines

Antiepileptics

Control of Epilepsy Medicines used in Status Epilepticus in Adults


Medicines Used in Parkinsonism and Related Disorders Dopaminergic medicines used in parkinsonism Antimuscarinic Medicines Medicines used in chorea, tics and related disorders Medicines Used in Substance Dependence Management of Alcohol Withdrawal Algorithm for prescription of vitamin supplementation in alcohol misusers Administration of IV Pabrinex Treatment of Withdrawal Cigarette Smoking Opioid Dependence


Benzodiazepine Policy BNF advice Benzodiazepines should only be prescribed for short term (2 - 4 weeks) relief of anxiety that is severe, disabling or subjects the individual to unacceptable distress. They should only be used for insomnia when it is severe, disabling or causing the patient extreme distress. If prescribed, benzodiazepines should be used in the lowest possible dose, for the shortest possible time, they should be reviewed regularly and discontinued as soon as possible.

Initiating Therapy Patients not previously prescribed benzodiazepines, and those who are not taking them on admission, should not be prescribed a benzodiazepine routinely, either as night sedation or for the management of generalised anxiety disorder (GAD). Do not offer a benzodiazepine for the treatment of GAD except as a short-term measure during crises. Follow the advice in the ‘British national formulary’ on the use of a benzodiazepine in this context, see NICE Guidance CG 113 Quick Reference Guide - Anxiety

Routine use of night sedation should be avoided, patients should be encouraged to take hypnotics on alternate nights and less frequently if possible

If night sedation is required before surgery, it should be prescribed for one night only.

Patients should be encouraged to sleep without medication; a hypnotic should not be routinely offered

Tolerance to hypnotics develops in 3 to 14 days

The lowest effective dose should be prescribed

Benzodiazepines be prescribed for a maximum of 5 days and only be on an 'as required' basis.

Chronic benzodiazepine users admitted to hospital should be allowed to continue treatment; medication histories should be confirmed as soon as possible for patients who are admitted to hospital and claim to be taking benzodiazepines,

Abrupt withdrawal may cause confusion, toxic psychosis, convulsions or a condition resembling delirium tremens

Hypnotics should not be used for acute behavioural disturbances.

Benzodiazepines should be avoided in the elderly since these patients are particularly at risk of becoming ataxic and confused and are likely to fall as a result

When a clinical need for therapy exists, consider the following:


http://guidance.nice.org.uk/CG113/QuickRefGuide/pdf/English


Alternative Strategies

Advise patients to avoid caffeine - containing drinks such as coffee and tea after 6pm. A hot milky drink is often helpful in inducing sleep.

Treat underlying medical and psychiatric problems, which may be causing anxiety and insomnia, e.g. adequate pain relief or antidepressants.

Psychological treatments including relaxation and CBT

Reassurance that 5 - 6 hours sleep at night for the elderly is normal, especially if the individual also `cat naps' during the day.

On Discharge

Patients should not be prescribed a benzodiazepine on discharge unless they have been medically assessed as a chronic user, or are taking them as part of terminal care treatment.

When a clear clinical need exists, the minimum quantity necessary should be prescribed and no more than 14 days treatment supplied

Patients on Long Term Therapy Benzodiazepines should be withdrawn gradually in any patient receiving them for longer than four weeks. When Considering Withdrawal:

Close liaison with the GP is essential. Check that the patient is not already undergoing a withdrawal schedule.

Withdraw the benzodiazepine over a four week period after a short course, i.e. less than four weeks.

A withdrawal period of several months may be necessary for a patient who has been taking benzodiazepines for several years. As a rough guide allow one or two months of withdrawal per year of taking the medicine.

Convert the patient to an equivalent daily dose of diazepam; preferably taken at night

Reduce the dose in steps of 2 to 2.5mg every 2 to 3 weeks; complete withdrawal may take several months


Approximate equivalent doses of benzodiazepines:

= chlordiazepoxide 15mg

= loprazolam 0.5 - 1mg

= lorazepam 500micrograms

= lormetazepam 0.5 - 1mg

= nitrazepam 5mg

= oxazepam 15mg

Diazepam 5mg

= temazepam 10mg

Advice should be available for patients wishing to discontinue benzodiazepines, including information concerning support groups. (For further advice see the current British National Formulary).

Hypnotics and anxiolytics

Hypnotics The medicine of choice in the Trust for the short term management of severe insomnia is Zopiclone, for further information see NICE Guidance TA77 Insomnia - newer hypnotic drugs: Quick reference guide and Trust Night Sedation Policy

Zopiclone Insomnia 7.5mg PRN nocte for a maximum of 5 nights Elderly patients 3.75mg nocte for a maximum of 5 nights

Lormetazepam tablets No longer recommended for insomnia in the Trust – treated as a Controlled Drug

Temazepam CD tablets/syrup

Insomnia: 10mg at bedtime. For patients already prescribed this medication on admission only

Anxiolytics

Diazepam By mouth, 2mg tablets/syrup 3 times daily increased if necessary to 15 - 30mg daily in divided doses. Elderly, half adult dose.

Propranolol Anxiety with palpitations, sweating, tremor: 40mg tablets/syrup once daily increased to 3 times daily if necessary.


http://www.nice.org.uk/nicemedia/pdf/TA077quickrefguide.pdf

http://www.nice.org.uk/nicemedia/pdf/TA077quickrefguide.pdf

http://staffintranet/policy/?web=64&sub=80&page=1351

Medicines Used in Psychoses and Related Disorders All antipsychotics used for psychoses are to be prescribed by psychiatrists only. The uses of the following medicines are for conditions other than psychoses. The choice of antipsychotic should be based on the required clinical effect e.g. sedation and side effect profile. Side Effect Profile of commonly prescribed antipsychotics

Medicine Anticholinergic effects Cardiac effects Extrapyramidal effects

Sedative effects

Chlorpromazine +++ ++ ++ +++

Levomepromazine +++ ++ ++ +++

Promazine ++ ++ + ++

Haloperidol + ++ +++ +

Amisulpiride 0 0 + 0

Sulpiride + 0 + +

Olanzapine + 0 0 ++

Quetiapine + + 0 +

Risperidone 0 0 + +

Antipsychotic medicines Once the patient is stabilised, the long half lives of these medicines allows the total daily dose to be given as a single night time dose in most patients. Use with caution in epilepsy, cardiovascular disease, hepatic impairment and Parkinsonism. For further information see NICE Guidance: CG 38 Bipolar disorder Quick reference guide

BNF Advice Antipsychotic medicines for the elderly

Antipsychotic medicines should not be used in elderly patients to treat mild to moderate psychiatric symptoms

Initial doses in elderly patients should be reduced to half the usual adult dose, or less, taking into account the patients weight, co-morbidities and concomitant medication

Treatment should be reviewed regularly


http://www.nice.org.uk/nicemedia/pdf/CG038quickrefguide.pdf

Rapid tranquillisation For further information see NICE Guidance: CG 25 Violence Quick reference guide Intervention Minimum Effective

Dose Maximum dose per 24 hours

Additional Information

Step 1

De-escalation, time out

Step 2

Offer Oral Treatment

Lorazepam (tablets) 1 – 2mg (elderly or debilitated half adult dose)

4mg (elderly or debilitated half adult dose)

If patient already receiving a benzodiazepine give antipsychotic. Peak serum level reached in 2 hours

Haloperidol (tablets or syrup) 5-10mg (elderly or debilitated initially half adult dose

30mg Risk of dystonic reactions increased in neuroleptic naïve and young patients (reverse with procyclidine injection)

Olanzapine (tablets or orodispersible tablets) 5 – 10mg

20mg MHRA has advised that olanzapine should not be used for treating behavioural symptoms of dementia due to increased risk of stroke. Peak plasma concentrations in 5 – 8 hours

Step 3

Consider IM treatment

Lorazepam IM Injection 1 – 2mg (elderly or debilitated half adult dose)

4mg (elderly or debilitated half adult dose)

Lorazepam injection must be diluted 1: 1 with water for injection for IM injection Stored in refrigerator

Haloperidol IM injection 5-10mg (elderly or debilitated initially half adult dose)

18mg Risk of dystonic reactions increased in neuroleptic naïve and young patients (reverse with procyclidine injection)

Step 4

Seek expert mental health advice

Atypical antipsychotic drugs For initiation by specialists in mental health only

Clozapine tablets If doses are missed for 48 hours or longer then the dose must be re-titrated starting with 12.5mg od or bd due to the risk of collapse from hypotension


http://www.nice.org.uk/nicemedia/pdf/cg025quickrefguide.pdf

Atypical antipsychotics and stroke Olanzapine and risperidone are associated with an increased risk of stroke in elderly patients with dementia. The MHRA has advised:

Risperidone or olanzapine should not be used for treating behavioural symptoms of dementia

For acute psychotic conditions in elderly patients with dementia risperidone should be limited to short-term use under specialist advice; olanzapine is not licensed for acute psychoses

The possibility of cerebrovascular events should be considered before treating any patient with a history of stroke or TIA

Other uses of antipsychotics Intractable hiccup: Chlorpromazine – oral 25-50mg 3-4 times daily Haloperidol – oral 1.5mg 3 times daily

Antipsychotic Depot Injections For initiation by specialists in mental health only

Antimanic medicines

Lithium salts

Lithium carbonate tablets/ s/r tablets

(s) Consultants only. Thyroid and therapeutic concentration monitoring is advised. Avoid co - administration with diuretics as sodium depletion potentiates toxicity. Avoid co-prescription of NSAIDs – increased risk of toxicity. Prescribe by brand name only.

Priadel s/r tablets 200mg (equivalent to 5.4mmol lithium) 400mg (equivalent to 10.8mmol lithium)

Camcolit tablet/ s/r tablets

250mg (equivalent to 6.8mmol lithium) 400mg (equivalent to 10.8mmol lithium)

Lithium citrate liquid (Priadel).

(s) Consultants only. 520mg/5mL (approx.5.4mmol lithium/5mL)

N.B: Monitor plasma - lithium levels regularly (click here for therapeutic concentration monitoring) especially if patient is also taking medication which may interact and increase toxicity (see BNF appendix 1).


Antidepressant Medicines Patients should be reviewed every 1-2 weeks at the start of antidepressant treatment. Treatment should be continued for at least 4 weeks before considering whether to switch antidepressant due to lack of efficacy. Following remission antidepressants should be continued at the same dose for at least 6 months. Patients with recurrent depression should continue to receive maintenance treatment for at least 2 years. Do not use antidepressants routinely to treat subthreshold depressive symptoms or mild depression in patients with a chronic physical health problem (because the risk–benefit ratio is poor), but consider them for patients with:

– a past history of moderate or severe depression or – mild depression that complicates the care of the physical health problem or – initial presentation of subthreshold depressive symptoms that have been

present for a long period (typically at least 2 years) or – subthreshold depressive symptoms or mild depression that persist(s) after

other interventions. When an antidepressant is to be prescribed for a patient with depression and a chronic physical health problem, take into account the following:

– the presence of additional physical health disorders – the side effects of antidepressants, which may impact on the underlying

physical disease (in particular, SSRIs may result in or exacerbate hyponatraemia, especially in older people)

– that there is no evidence as yet supporting the use of specific antidepressants for patients with particular chronic physical health problems

– interactions with other medications. For further information see NICE guidance: CG90 Depression in adults: quick reference guide The choice of antidepressant medicine depends mainly on the side effect profile.

Medicine Anticholinergic effects Cardiac effects Sedative effects

Epileptogenic effects

Amitriptyline +++ +++ +++ ++

Dosulepin [Dothiepin]

++ ++ +++ ++

Lofepramine ++ + + 0

Citalopram / Escitalopram

0 0 0 0

Fluoxetine 0 0 0 0

Mirtazapine 0 0 ++ ++

Venlafaxine 0 ++ + +




Arrhythmias and heart block occasionally follow the use of tricyclic antidepressants, especially amitriptyline and should therefore be used with extreme caution in patients with cardiac disease. The use of tricyclic antidepressants is contra - indicated in patients with arrhythmias or recent myocardial infarction.

BNF Advice Hyponatraemia, (usually in the elderly) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions whilst taking an antidepressant.

Tricyclic and related antidepressant medicines

Amitriptyline tablets/ solution

Initially 75mg (elderly 30 - 75mg) daily at night increased gradually as necessary to max. 150mg.

Lofepramine tablets / suspension

140 – 210mg daily in divided doses. Elderly patients often respond tablets/syrup to lower doses.

Selective Serotonin Re - Uptake Inhibitors

Fluoxetine capsules / liquid

20mg daily in the morning.

Citalopram tablets / oral drops

20mg daily (8 drops liquid equivalent to 20mg tablet)

Medicines used in the treatment of obesity

Appetite Suppressants The development of obesity is multi - factorial. Aggravating factors may be medicine treatment, depression or other psycho - social problems. Medicines in the treatment of obesity can play only a limited role and should never be used as the sole element of treatment. Appetite suppressants may only be prescribed by consultants after referral to a specialist clinic. For further information see NICE guidance: CG 43 Obesity;

Medicines Used in Nausea and Vertigo Symptomatic Relief from Underlying Cause Anti - emetics should be prescribed only when the cause of nausea or vomiting is known, as the symptomatic relief they produce may delay correct diagnosis. The choice of medicine then depends on the aetiology of vomiting. See here for adjunctive therapy for anti - emetic prescribing in palliative care.


http://www.nice.org.uk/nicemedia/pdf/word/CG43NICEGuideline.doc

Extrapyramidal side effects are seen with prochlorperazine, metoclopramide and domperidone. Acute dystonic reactions with facial and skeletal muscle spasms and oculogyric crises are more common in the young (especially women) and the very old.

Prochlorperazine tablets/syrup/ injection

By mouth, 5 - 10mg 2 - 3 times daily. By deep i.m. injection, 12.5mg when required every 4 - 6 hours.

N.B: Always indicate route of administration when prescribing since doses are different. Metoclopramide has a peripheral action on the gut as well as action at the chemoreceptor trigger zone and is therefore the anti - emetic of choice for gastroduodenal, hepatic and biliary disease. Do not use if gastrointestinal obstruction is suspected. N.B. in patients less than 20 years of age, use is restricted to severe intractable vomiting due to risk of dystonic reactions..

Metoclopramide tablets/syrup/injection

By mouth, 10mg 3 times daily (5mg 3 times daily if less than 20 years old). By i.m./i.v. injection, 10mg 3 times daily.

Domperidone has a similar central and peripheral action to metoclopramide but is less likely to cause central side effects such as sedation and dystonic reactions, since it does not readily cross the blood brain barrier. It is therefore the anti-emetic of choice in Parkinson's disease.

Domperidone tablets/ suspension / suppositories

By mouth, acute nausea and vomiting (including that induced by levodopa) 10 - 20mg every 3-4 times daily By rectum, 60mg twice a day

Hyoscine is the most effective medicine for motion sickness. It may also be used for vertigo and nausea associated with Ménière's Disease and middle ear surgery.

Hyoscine hydrobromide tablets

(s) ENT and Consultants only. May be used sublingually.

Cyclizine is an antihistamine, which acts on the vomiting centre. It is more sedating than other anti - emetics. It may aggravate heart failure.

Cyclizine tablets/injection By mouth, 50mg up to 3 times daily. By i.m. or i.v. injection, 50mg up to 3 times daily.

Vomiting during pregnancy Recommended stepwise treatment of nausea and vomiting in pregnancy:

Step 1: (non-pharmacological management) – small, high carbohydrate, low fat, frequent meals and P6 (wrist) accupressure

Step 2: (first-line medicines) - cyclizine or promethazine Step 3: (second-line medicines) - prochlorperazine or metoclopramide Step 4: (treatment resistant symptoms) consider ondansetron



Other medicines for Meniere’s disease

Betahistine tablets Initially 16mg TDS with food; maintenance dose 24 – 48mg daily Cost band for 28 days (16mg TDS): B

Guidelines for Chemotherapy - induced Nausea and Vomiting 1. Anti - emetics are best given regularly and before chemotherapy. Ondansetron should be

administered just before treatment, if given IV, and 1 hour before if given orally.

2. Dexamethasone may be used to prevent, but not to treat emesis. If the patient is already taking corticosteroids, seek advice on the use of this medicine.

3. If the patient fails on current treatment, move to the next anti - emetic regimen.

4. Consider the use of oral cyclizine 50mg three times daily if necessary.

5. If delayed emesis is likely, use prophylactic anti - emetics instead of "as required" doses. Ondansetron should not be used for this purpose.

6. If anticipatory nausea and vomiting occurs, give lorazepam 1mg the night before and on the morning of chemotherapy. Note: Counsel the patient on the possibility of drowsiness with this medicine.

7. Other possible oral anti - emetic agents include prochlorperazine 5mg three times daily, haloperidol 1.5mg twice daily and levomepromazine [methotrimeprazine] 12.5mg twice daily.

Choice of Anti - emetic for Regimens of Low, Moderate and High Risk of Emesis

Low Emetic Risk Moderate Emetic Risk High Emetic Risk

First line schedule Prior to chemotherapy:

Dexamethasone 8mg iv +/- Metoclopramide 10mg iv

Then

Dexamethasone 4mg po t.d.s. with Metoclopramide 20mg po t.d.s. or

domperidone 20mg po t.d.s. for 3 - 5 days.

Anti - emetics should be prescribed regularly to prevent delayed emesis.

First line schedule Prior to chemotherapy:

Ondansetron 8mg iv +/- dexamethasone 8mg iv

Then

Ondansetron 8mg po b.d. +/- dexamethasone 4mg po t.d.s.

Post chemotherapy switch to:

Metoclopramide 10 - 20mg po/iv t.d.s. regularly to prevent delayed emesis.

Exceptions to this schedule are patients receiving high dose chemotherapy with TBI (Total Body Irradiation). Use ondansetron 16mg iv +/- dexamethasone 4 - 12mg iv over 24 hours if indicated (review daily).

Regular anti - emetics may not be routinely required.

If necessary, give metoclopramide 10mg iv prior to chemotherapy.

If symptoms develop, then: metoclopramide 10 -

20mg po/iv t.d.s. or domperidone 10 -

20mg po t.d.s. or domperidone 30mg

PR t.d.s.

Second line schedule If anti - emetics fail in the acute period (i.e. first 24 hours or before chemotherapy complete)

Next cycle, prior to chemotherapy: Ondansetron 8mg iv

Then Ondansetron 8mg po b.d. for 3 days. Switch to metoclopramide 10mg po

t.d.s. or domperidone 10mg po t.d.s. post chemotherapy for 3 days.

Second line schedule If anti - emetics fail in the acute period (i.e. first 24 hours or before chemotherapy complete), add lorazepam 1 - 2mg po/iv stat. (Failure = one vomit or > 4 hours of distressing nausea).


Assessing the Emetogenicity of a Regimen

1. A regimen containing any agent that is high risk should be classified as highly emetogenic.

2. A regimen containing two or more moderate risk agents should be classified as highly emetogenic.

3. A regimen containing one moderate risk agent plus any number of low risk agents should be classified as moderately emetogenic.

4. A regimen containing one or more low risk agents should be classified as having low emetogenicity.

Risk of Emesis with Single or Combination Cytotoxic Regimens

Low Risk:- Regimens Containing One or More of the Following Time to onset of symptoms (hours)

Asparaginase 1 - 3

Bleomycin 3 - 6

Bulsulphan

Chlorambucil 48 - 72

Cladribine

Fludarabine

5 – Fluorouracil 3- 6

Gemcitabine

Hydroxycarbamide [hydroxyurea] 6 - 12

Melphalan (po) 6 - 12

Mercaptopurine (po) 4 - 8

Methotrexate < 50mg/m2 4-12

Tioguanine [thioguanine ] (po) 4 - 8

Thiotepa 6 - 12

Vinblastine 4 - 8

Vincristine 4 - 8

Vindesine


Moderate Risk:- Regimens Containing One or More of the Following + any Low Risk agents Time to onset of symptoms (hours)

Amsacrine

Cyclophosphamide (po)

Cyclophosphamide IV < 750mg/m2 4 -12

Cytarabine < 1g/m2 6 – 12

Dactinomycin 2 - 6

Docetaxel

Daunorubicin 2 - 6

Doxorubicin 4 - 6

Epirubicin

Etoposide 3 - 8

Idarubicin

Ifosfamide <1.5g/m2

Melphalan <100mg

Methotrexate >50mg/m2

Mitomycin 1 - 4

Mitoxantrone

Paclitaxel

Pentostatin (deoxycoformycin)

Procarbazine (po) 24 - 27

Raltitrexed


High Risk:- Regimens Containing One or More of the Following or two or more Moderate Risk agents Time to onset of symptoms (hours)

Busulfan 40mg

Carboplatin

Carmustine (2 - 4) hours

Cisplatin (1 - 6) hours

Cyclophosphamide IV >750mg/m2

Cytarabine >1g/m2

Dacarbazine (1 - 3) hours

Ifosfamide>1.5g/m2 (1 – 2)

Lomustine

Melphalan >100mg

Mustine (0.5 - 2)

Streptozocin (1 - 4)

Metoclopramide Injection

By continuous IV infusion, initially (before starting chemotherapy) 2 - 4mg/kg in 50 - 100mL glucose 5% or sodium chloride 0.9% over 15 - 30 mins then 3 - 5mg/kg in 500mL glucose 5% or sodium chloride 0.9% over 8 - 12 hours. Max. 10mg/kg in 24 hours.

Ondansetron tablets/injection

Moderately emetogenic chemotherapy or radio-therapy: By mouth, 8mg 1 - 2 hours before treatment or By slow IV injection, 8mg immediately before treatment, then 8mg orally every 12 hours for up to 5 days. Severely emetogenic chemotherapy or radiotherapy: By slow IV injection, 8mg immediately before treatment, followed by 8mg at intervals of 2 - 4 hours for 2 further doses. Then 8mg by mouth every 12 hours for up to 5 days.

Dexamethasone tablets/syrup/injection

Use as adjunct to metoclopramide or ondansetron: 8mg IV before chemotherapy, then 2mg orally 3 times daily post chemotherapy for 3 days or according to unit protocols.


Guidelines for the Management of Post Operative Nausea & Vomiting

PONV Assessment Score

0 No nausea or vomiting

1 Mild nausea. No vomiting

2 Moderate nausea and\or occasional vomiting

3 Severe nausea and\or frequent vomiting


Analgesics (See here for assessment and management of acute pain) Management of Acute Pain Pain is a complex physiological and psychological sensation, which acts as a warning sign. The pain tolerance differs between individuals and can be affected by a number of factors. Factors that lower the pain tolerance include insomnia, anxiety, fear, isolation, depression and boredom. Treatment of pain is dependent on cause, type (musculoskeletal or visceral), duration (acute or chronic) and severity. See here for management of pain in palliative care. Principles of Pain Management

Pain is what the patient says it is and should be treated to the patient's satisfaction.

Accurately diagnose cause of pain.

Prescribe according to the W.H.O. analgesic ladder. (here)

Use REGULAR analgesia once source of pain is diagnosed.

Set realistic goals by negotiation with the patient.

Re - assess frequently.

Consider non - medicine treatment.

Give analgesics REGULARLY before consideration is given to moving up the analgesic ladder.

Non–opioid analgesics Non-steroidal anti-inflammatory drugs (NSAIDs) are the analgesics of choice for musculoskeletal pain especially if there is an inflammatory component or bone pain. All NSAIDs are gastric irritants regardless of the route of administration, naproxen or ibuprofen in the lowest possible doses are associated with the lowest risk of GI side effects. Consider prophylaxis against gastrointestinal ulceration if administration is likely to be chronic. Use with extreme caution in asthmatics. The use of NSAIDs is contra - indicated in asthmatics that have a known hypersensitivity to aspirin or other NSAIDs. Use with caution in the elderly and in patients with renal impairment. NSAIDs may be associated with an increased risk of thrombotic events; assess cardiovascular risk before prescribing.

Paracetamol Infusion 10mg/mL

For use only when the oral route is not available


Compound Analgesic Preparations Co – prescribing of compound analgesics with paracetamol on a when required basis has led to overdose of paracetamol.

Opioid analgesics

Diamorphine CD injection

Acute pain: By s.c. or i.m. injection, 5mg repeated every 4 hours if necessary. By slow i.v. injection, 1.25 – 2.5mg every 4 hours if necessary. Myocardial infarction: By slow i.v. injection, (1mg/min), 5mg (elderly or frail patients 2.5mg) followed by a further 2.5 – 5mg (elderly or frail patients 1.25 – 2.5mg) if necessary. Acute pulmonary oedema: By slow i.v. injection, 2.5 – 5mg.

Morphine sulphate CD Acute pain: By s.c. or i.m. injection, 10mg (elderly or frail patients 5mg) every 4 hours if necessary. By slow i.v. injection, 2.5 mg (elderly or frail patients 1.25mg) every 4 hours if necessary. Myocardial infarction: By slow i.v. injection, (1mg/min) 10mg (elderly or frail patients 5mg) followed by a further 5 – 10mg (elderly or frail patients 2.5 – 5mg) if necessary. Acute pulmonary oedema: By slow i.v. injection, 5 – 10mg.

Fentayl sublingual tablets (Abstarl),

Pain team only

Oxycodone CD tablets/capsules/ injection

Pain Team and Palliative Care Team only.

Pethidine CD tablets/injection

Pethidine is inappropriate for routine use due to its short action. It should be avoided in patients with renal failure. Accumulation of metabolites may result in neurotoxicity

Tramadol – recommendations for use

Treatment with tramadol should be short and intermittent and only for moderate to severe pain

Tramadol should be used with great caution in patients with a history of dependence


Patients with epilepsy or a history of epilepsy should only be treated if there are compelling reasons

Tramadol should be used with caution in patients taking medication that can lower the seizure threshold, particularly serotonin re - uptake inhibitors and tricyclic antidepressants.

Tramadol capsules/ s/r capsules/ injection

50mg – 100mg every 4 hour – usual maximum 400mg in 24 hours

Ketorolac injection/tablets

(s) Anaesthetists and A&E only.

Equivalent Doses of Opioid Analgesics Click here for opioid dose conversion ratios.

Neuropathic pain

1st line Gabapentin capsules

300mg single dose on day 1, 300mg BD on day 2, 300mg TDS on day 3. Increase according to response to maximum 3.6g daily.

2nd line Pregabalin capsules

(s) Consultants only, pain clinic and Diabetologists

Post Herpetic Neuralgia

Amitriptyline tablets Start with 25mg, (10mg in the elderly) taken in the early evening to avoid hangover effect. Pain relief may begin in 1 – 7 days. Rate of increase depends on pain level and degree of supervision. If tolerated dose may be increased by about 25mg every three days to 75mg at night. Elderly: rate of increase may need to be slower e.g. 25mg per week.

Capsaicin cream 0.075% (Axsain)

(s) Consultants only. Note: only to be used after lesions have healed.


Antimigraine Medicines Treatment of the acute migraine attack Analgesics

Paracetamol PLUS Metoclopramide

500mg - 1g every 4 - 6 hours when required. Max 4g daily.10mg 3 times daily when required.

Ibuprofen PLUS Metoclopramide

400mg 3 times daily when required. 10mg 3 times daily when required.

Note: Products combining a simple analgesic with an anti – emetic, e.g. Migraleve, have not been shown to be any more effective than the above regimens and are considerably more expensive. 5HT1 agonists

Sumatriptan tablets/injection

(s) Consultant and A & E use only.

Prophylaxis of migraine

Propranolol tablets / m/r capsules

Ensure no contra - indications apply e.g. asthma. 80mg daily in single or divided doses according to preparation. May be gradually increased to max. 240mg daily if necessary.

Pizotifen tablets Useful when there is a contra - indication or unacceptable side effects to propranolol. Note: Causes weight gain. Dose: 1.5mg daily increasing to 3mg if necessary.


Antiepileptics (Click here for therapeutic level monitoring)

Control of Epilepsy Use monotherapy whenever possible, if one treatment is unsuccessful due to seizures or adverse effects try monotherapy with another medicine. Care must be used to build up to an adequate or tolerated dose of the second medicine and then taper off the first medicine slowly. A neurology opinion should be sought before initiating antiepileptic medication. For further information see NICE Guidance: CG20 Epilepsy in adults: Quick reference guide Maintenance doses of antiepileptic medicines should not be prescribed for alcohol induced seizures as there is no evidence that they are effective in preventing further seizures.

Partial Seizures Sodium valproate, Carbamazepine and Lamotrigine can be used as monotherapy.

Generalised Seizures

Tonic Clonic Carbamazepine, lamotrigine, sodium valproate.

Absence seizures Sodium valproate, especially if co – exists with tonic-clonic seizures, lamotrigine.

Myoclonic Sodium valproate

Carbamazepine suppositories/ tablets/ MR tablets/ liquid

By mouth, initially 100 - 200mg 1 - 2 times daily and build up slowly in increments of 100 – 200mg every 2 weeks to a usual dose of 0.8 - 1.2g daily in divided doses. By rectum, short term use (seven days max) 125mg approximately equivalent to 100mg by mouth. Max. dose by rectum is 250mg 4 times daily for up to 7 days. Serum level monitoring is recommended.

Lamotrigine tablets (s) Consultants only.

Phenytoin capsules/ suspension/injection

No longer recommended as a first line antiepileptic medicine for maintenance treatment of any seizure type. 100mg capsules are equivalent to 90mg (15mL) of 30mg/5ml syrup. By i.v. injection, same dose as by oral route administered into large peripheral vein, no faster than 50mg/min with ECG monitoring. Method of administration, click here


http://www.nice.org.uk/guidance/index.jsp?action=download&o=29529

Sodium valproate / valproic acid tablets/liquid/injection

By mouth, initially 600mg daily in divided doses preferably after food, increasing by 200mg/day at 3 day intervals to a max. of 2.5g daily in divided doses. Usual maintenance 1 - 2g daily. By IV injection, by short i.v. infusion over 30 minutes for continuation of valproate treatment when oral therapy not possible. Give at same dose as current oral dose.

Sodium valproate M/R Prescribe by brand name (e.g. Epilim Chrono). By mouth, initially 600mg daily increasing by 200mg/day at 3 day intervals to a max of 2.5g daily in divided doses. Usual maintenance 1 - 2g daily. Total daily dose given in 1 to 2 divided doses.

Medicines used in status epilepticus

Management of Major Status Epilepticus in Adults

Initial Management

For further information see NICE guidance Treatment of Status Epilepticus

Turn to lateral semi-prone position and protect airway if needed (extend neck).

Appropriate management of airways, breathing and circulation. Give oxygen 35 - 40% by face mask Establish IV access, if this fails consider the rectal route. Lorazepam 4mg I.V bolus (first choice) alternatively intravenous

diazepam (Diazemuls) at a dose of 10mg If no i.v. access give diazepam 10-20mg rectally (Stesolid rectal

tubes). Note: Risk of respiratory depression with all benzodiazepines. Monitor B.P Take blood for U&E, glucose, anti - epileptic medicine levels,

calcium, magnesium, FBC. Measure blood gases to assess acidosis


http://www.nice.org.uk/nicemedia/pdf/CG020fullguideline_appendixC_corrected.pdf

http://www.nice.org.uk/nicemedia/pdf/CG020fullguideline_appendixC_corrected.pdf

Management of Major Status Epilepticus in Adults

Subsequent Management

Repeat Lorazepam 4mg IV after 10 minutes Phenytoin 15mg/kg loading dose, administered into large

peripheral vein, no faster than 50mg/min with BP and ECG monitoring, (risk of arrhythmias)

Method of administration of phenytoin, either by syringe pump, or direct injection, without dilution. Flush line with sodium chloride 0.9% before and after infusion. Note: Max. rate 50mg/min. Or: By minibag, in100 - 250mL sodium chloride 0.9% only. Final concentration must not exceed10mg/mL. Use an in line filter (0.22 - 0.50micron) and administer over 20-40 mins (max. rate 50mg/min) but no longer than one hour. Flush line with sodium chloride 0.9% before and after infusion. N.B: Filter can be used for up to 72 hours.

Hypoglycaemia give 250ml of 10% glucose History of alcohol abuse give 2 pairs ampoules IV Pabrinex

Refractory Contact Anaesthetist on call. Propofol or Thiopental as on the advice of anaesthetist.


Medicines Used in Parkinsonism and Related Disorders

Dopaminergic medicines used in parkinsonism The recommended ratio of dopa - decarboxylase inhibitor to levodopa is 1:4 in order to achieve sufficient inhibition of extracerebral dopa - decarboxylase. Co - careldopa 25/100 (Sinemet Plus) provides low dose levodopa (100mg) with sufficient decarboxylase inhibitor (25mg) for initial therapy. Co - careldopa 10/100 (Sinemet - 110) and Co - careldopa 75/200 (Sinemet - 275) are NOT appropriate preparations for initial therapy. Domperidone may be used to control the nausea associated with levodopa therapy. Some medicines in this section are restricted to consultant initiation only due to the difficulty in diagnosing Parkinson's disease. For further information see NICE guidance: CG 35 Parkinson's disease Quick reference guide

Apomorphine Injection (s) Lead Consultant for Parkinson’s Disease only

Co - beneldopa (Madopar) capsules/soluble tablets/ m/r capsules

Co - careldopa (Sinemet) tablets/ m/r tablets

Entacapone tablets (s) Lead Consultant for Parkinson’s Disease only.

Pramipexole tablets (s) Lead Consultant for Parkinson’s Disease only

Ropinirole tablets (s) Lead Consultant for Parkinson’s Disease only

Rotigotine patches (s) Lead Consultant for Parkinson’s Disease only

Selegiline tablets/syrup/lyophilisate

(s) Lead Consultant for Parkinson’s Disease only Selegeline 10mg (conventional) is equivalent to selegeline lyophilisate 1.25mg(Zelapar)

Stalevo ® tablets (s) . Lead Consultant for Parkinson’s Disease only Co-careldopa with entacapone. 50/12.5/200mg; 100/25/200mg and150/37.5/200mg. To replace entacapone plus co-careldopa regimens with improvement in patient compliance.

Other preparations available on consultant request.




Antimuscarinic Medicines

Procyclidine tablets/syrup/injection

To treat medicine induced extrapyramidal effects: By mouth, 2.5mg 3 times daily gradually increased if necessary to max. 30mg daily. Acute dystonia: By i.m or i.v.. Injection, 5 - 10mg repeated if necessary after 20 mins. (usually effective in 5 -10 minutes but may need 30 minutes for relief)

Medicines used in chorea, tics and related disorders Haloperidol

tablets/liquid Motor tics: 0.5 - 1.5mg 3 times daily adjusted according to response.

N.B: Not for use in tremors related to Parkinson's disease


Medicines Used in Substance Dependence

Alcohol withdrawal ranges from an insignificant upset to a life - threatening syndrome with delirium, fits and serious neurological complications.

Withdrawal symptoms may start around 3 - 6 hours after stopping drinking and can last 5 - 7 days, sometimes longer.

Up to 12 hours after the last drink symptoms may include tremor, sweating, anorexia, nausea, insomnia and anxiety.

Between 10 and 60 hours, alcohol withdrawal seizures are a risk and may precede or accompany delirium tremens. Predisposing factors include hypoglycaemia, hypokalaemia, hypomagnesaemia and epilepsy.

Patients with thiamine deficiency may develop Wernicke's encephalopathy, which is characterised by confusion, ataxia, memory disturbance and ophthalmoplegia. Patients may then develop Korsakoff's syndrome, where they have difficulty acquiring new memories.

Management of Alcohol Withdrawal

General Support Initial investigation should include estimation of blood urea and electrolytes, glucose, amylase, calcium, magnesium, blood gases and LFTs. Blood glucose should be monitored frequently in severe cases. Rehydration and correction of hypoglycaemia, hypokalaemia and hypomagnesaemia are essential. Note: A glucose load (sweet food or IV glucose) can precipitate Wernicke's encephalopathy in a thiamine deficient patient, so IV Pabrinex must be given to all high risk patients as in the flow chart below.

Thiamine Deficiency The algorithm on the next page describes the treatment of established Wernicke’s encephalopathy and those deemed to be at high risk.

All patients should be prescribed:

Thiamine tablets 100mg TDS (doses should be split in this way to maximise absorption)

PLUS

Multivitamin tablets One or two daily.

Continue upon discharge only if the patient’s diet is inadequate


Refer all patients who are encephalopathic to a gastroenterologist Algorithm for prescription of vitamin supplementation in alcohol misusers Patients who abuse alcohol are at risk of developing Wernicke’s encephalopathy as a result of poor dietary intake of thiamine. Thiamine absorption is mediated by a saturable transport mechanism (the maximum amount absorbed from an oral dose is approx. 8mg). Therefore oral thiamine doses should be split – patients will absorb more if they are given 100mg TDS than if they are given 300mg OD. The algorithm below describes the vitamin supplementation required by alcohol misusers admitted for detoxification.

Diagnosis of Wernicke’s/ Assessment of Risk Established Wernicke’s encephalopathy is usually characterised by confusion

± ataxia, memory disturbance and ophthalmoplegia. However, in many cases, these classical signs may not be present, and therefore, it is always important to consider the possibility that the patient may have Wernicke’s encephalopathy.

High risk patients include: o Those who present with significant weight loss and/or show signs of

under-nutrition o Severe withdrawal o Increasing memory problems/black outs o Are in a coma or present with confusion o Patients who present with hypoglycaemia (and are treated with IV

glucose) with evidence of chronic alcohol ingestion must be given IV Pabrinex due to the risk of precipitating Wernicke’s encephalopathy.

Low Risk

Established Wernicke’s /

High Risk

Give 2 pairs Pabrinex ampoules IV three times a

day for 3 days. This may be reduced to 1 pair daily for 3-

5 days if the patient responds.

Give thiamine 100mg TDS and multivitamins 1 tablet daily. Continue upon discharge only if the patient’s diet is inadequate.

Known/suspected alcohol misuser


Administration of IV Pabrinex Pair(s) should be added to 50-100ml of saline 0.9% or glucose 5% and infused over 30 minutes to reduce the risk of anaphylactic reactions. Facilities to manage anaphylaxis should be made available before the dose is administered.

Treatment of Alcohol Withdrawal It is important to avoid a) inadequate treatment, which may lead to Delirium Tremens or seizures and b) over treatment, which may lead to over sedation and respiratory depression. Early detection and prompt initiation of treatment is crucial as untreated acute alcohol withdrawal can progress to delirium tremens, which has been shown to be fatal in 15-20% of untreated patients. If untreated, death may result from respiratory and cardiovascular collapse or cardiac arrhythmias. Patients most at risk are those with a high fever (>104°F/39.9°C), tachycardia, dehydration and an associated illness (e.g. pneumonia or pancreatitis), general debility or where the diagnosis is delayed. However, appropriate management reduces mortality to around 1%. In most cases this can be achieved with oral benzodiazepines, usually chlordiazepoxide. Because of the psychological impact of detoxification planning and coordination with alcohol follow-up services is essential. Good nursing care in a well lit, cool environment has been shown to reduce the impact of sensory deprivation on the confused patient, and as such is a crucial part of the treatment plan. Benzodiazepines, particularly chlordiazepoxide, are central to the management of alcohol withdrawal and have the following important properties: Sedative, anxiolytic, anticonvulsant, cross-tolerant with alcohol, and do not induce liver enzymes. The Adapted Clinical Institute Withdrawal Assessment tool (CIWA-AD) will be used by the senior doctors or ASN to provide guidance for dosage level. Chlordiazepoxide will then be prescribed on the PRN or variable dose section of the patient prescription/drug chart.


Oral Chlordiazepoxide Symptom Triggered Regime

The presence of jaundice, encephalopathy, ascites, bleeding, prolonged prothrombin time >17 seconds, low serum albumin <30g/l or urea >10mmol/l should alert the clinician to the possibility of significant or decompensated liver disease. The dose of chlordiazepoxide should be halved in significant liver disease. Benzodiazepines should be avoided if hepatic encephalopathy is present or if decompensation is incipient. The Hepatology team or on-call Gastroenterology registrar on-call should be contacted urgently.

CIWA- AD Score Oral Chlordiazepoxide

CIWA-AD Score

Less than 9 NIL Repeat in 1 hour Score of 9 to 11 10 to 20mg Repeat in 1 hour Score of 12 or greater 25 to 30 mg Repeat in 1 hour

When patient symptoms are controlled assessment can be four hourly.

Oral Thiamine 100mg three times daily should be commenced. OR

If confusion, ataxia, ophthalmoplegia or BMI less than 20 with recent

Tachycardia A non - selective beta - blocker e.g. Propranolol may decrease the risk of arrhythmias and help where tachycardia and tremor are prominent. Propranolol m/r 80mg daily, increasing to propranolol m/r 320mg daily if required, may allow a lower dose of sedative to be used. Care should be taken if the patient has co - existing cardiovascular or respiratory problems. Seizures

Alcohol withdrawal seizures or status epilepticus should be treated with lorazepam 4mg I.V bolus (first choice) alternatively intravenous diazepam (Diazemuls) at a dose of 10mg

If no i.v. access give diazepam 10-20mg rectally (Stesolid rectal tubes). Maintenance antiepileptic medication should not be prescribed as there is no evidence that it reduces the incidence of alcohol withdrawal seizures. Psychiatric Syndromes A variety of psychiatric syndromes may manifest once a patient has recovered from the acute withdrawal state, e.g. paranoid psychosis, memory difficulties, and affective disorders. A psychiatric consultation is advisable when persistent auditory hallucinations and/or delusions are noted, or when an affective disorder is suspected. Home Detoxification Programmes The management of acute alcohol withdrawal in the community setting can reduce a patient’s length of stay in hospital and may even prevent them being admitted into hospital. Patients eligible for home treatment To be suitable for home detoxification, the patient must satisfy the following criteria:

They must be medically fit for discharge (as determined by a doctor). They must be assessed by an alcohol specialist nurse regarding their

suitability for home detoxification. The result of this assessment will be documented in the case notes.

They must have support at home from either friends or relatives. Patients who live alone are not suitable.

Patients may only be discharged on days between Monday and Thursday.


Prescribing chlordiazepoxide on discharge prescriptions (TTO) If a patient is deemed suitable for home detoxification, chlordiazepoxide can be prescribed on their TTO.

Due to the nature of the reducing regimes, it is often difficult to put clear dosing instructions onto the pharmacy-dispensing label. Therefore, a patient information sheet (available from the alcohol specialist nurses) detailing the doses to be taken must be completed by the prescriber and sent to pharmacy with the TTO and medicine card for a pharmacist to clinically check. A copy of this sheet is also sent to the patient’s GP.

A maximum of 200mg of chlordiazepoxide can be prescribed/dispensed for an individual patient. Patients who require more than 200mg of chlordiazepoxide to complete their reducing regime need to have a prescription written by their GP for the remaining amount. The alcohol specialist nurses will liaise with the patient’s GP to arrange this.

For further information see Trust Policy: Managing Acute Alcohol Withdrawal and Delirium Tremens (available via intranet). Cigarette Smoking Smoking cessation products such as patches, chewing gum etc. should only be used as an adjunct to counselling. The Trust smoking cessation adviser can be contacted on 706 2332 and will come to the ward to advise patients.

Varenicline tablets Dr Burhan, smoking cessation specialist advice only


Opioid Dependence

Opioid withdrawal symptoms are unpleasant but not life threatening.

In contrast

Methadone overdose, or its administration to opioid - naive patients, can be fatal.

Opioid withdrawal is not a medical emergency, so methadone does not routinely need to be prescribed in the Accident and Emergency Department (unless there is objective evidence of opioid withdrawal symptoms).

In pregnancy, opioid or benzodiazepine withdrawal can precipitate serious foetal outcomes. Rapid stabilisation of symptoms is essential. For pregnant patients, please liaise urgently with the on - call obstetrics registrar at the Liverpool Women’s Hospital.

Doctors do not need a special licence to prescribe methadone in the management of drug dependence. However, a special licence issued by the Home Secretary is needed to prescribe, administer or supply diamorphine, dipipanone or cocaine in the treatment of drug dependence.

Doctors may still prescribe diamorphine, dipipanone or cocaine for patients, including addicts, for relief of pain due to organic disease or injury, without a special licence.

Opioid Withdrawal Symptoms

Occur When an opioid - dependant individual is without their usual source of opioid for a period of time.

Severity Is variable and depends on: 1. The amount of opioid usually taken. 2. Route of administration - usually more severe in intravenous users. 3. Psychological factors, e.g. coping strategies/anxiety.

Time of Onset Depends on the opioid used. Short - acting opioids: 6 - 8 hours after last use e.g. Heroin, morphine, and dihydrocodeine. Long - acting opioids: 16 - 24 hours after last use e.g. Methadone


Symptoms

Subjective:

Craving for opioids.

Anxiety symptoms.

Pains and cramps in muscles, particularly stomach, back and legs.

Unable to sleep.

Feeling hot and cold.

Objective:

Cold, sweating, clammy and goose flesh.

Yawning.

Nausea, vomiting and diarrhoea.

Restlessness and insomnia.

Tremor.

Lachrymation and rhinorrhea.

Raised BP and tachycardia.

Note:

1. These symptoms may occur in other medical conditions or co - exist with other conditions.

2. Seizures or fits do not occur in pure opioid withdrawal. 3. Drowsiness, sedation, disorientation or confusional states do not occur in

pure opioid withdrawal. 4. Pyrexia is not a symptom of opioid withdrawal. 5. Opioid withdrawal may be masked or attenuated by other medicines or

substances, e.g. benzodiazepines, barbiturates, alcohol, phenothiazines.


Managing Patients on “Street” Heroin or Unconfirmed Prescribed Methadone Dose. (Click here for methadone algorithm)

Take a urine sample and send to clinical chemistry for “opiates and methadone”.

Do not start methadone unless there is objective evidence of withdrawal symptoms.

Prescribe a single dose of methadone 10mg on the “once only” part of the prescription chart.

A second dose of methadone 10mg may be prescribed and given no sooner than four hours after the first dose.

The patient should not receive more than 20mg of methadone in the first twelve hours.

After this initial twelve hours, methadone may be prescribed as 20mg twice daily - maximum dose 40mg in 24 hours.

Write the dose in both words and figures to prevent unauthorised alterations Do not prescribe on a “when required basis”. Endorse the prescription “do not give if drowsy”. Do not give if patient is drowsy, sedated, ataxic, has slurred speech or is

asleep. Never wake a patient to give them methadone. Methadone doses should be prescribed in words and figures to prevent

patients from altering their prescriptions.


General Points Regarding Methadone Prescribing.

Oral methadone liquid should be prescribed, i.e. methadone mixture 1mg/ml.

If the parenteral route is unavoidable, methadone should be given IM. IV administration is unlicensed.

In those patients with true methadone intolerance, dihydrocodeine may be used. However, this is an unlicensed indication.

A patient’s usual dose of methadone must be confirmed with the clinic, GP or community pharmacy before prescribing, details of the confirmation must be documented in the case notes.

If patients have missed 72 hours or more of their usual dose of methadone the clinic should be contacted for advice regarding an appropriate dose. If it is not possible to contact the clinic e.g. at a weekend the follow the guidance above.

Dosing interval When in the community patients usually take their daily methadone as a single dose. Therefore there it is not necessary to have a minimum specified time interval between doses when the daily dose is divided into two and given twice daily while in hospital. However if the patient is showing signs of toxicity e.g. drowsiness, confusion further doses should be with held and senior medical advice sought.

Discharge issues: Patients with a history of IV drug abuse who are not registered on a

programme should not receive methadone on discharge. For patients registered on a methadone programme, the GP/clinic needs

to be informed at least 24 hours in advance of a patient’s discharge so they can arrange a further prescription.

Prescribe and administer a STAT dose of methadone (to make up the patient’s usual total daily dose) on the ward before discharge.

If a patient is discharged during a weekend, a TTO for up to 48 hours (72 hours in the case of a bank holiday) supply may be written.

All liaisons with the GP/clinic must be documented in the case notes.

Analgesia prescriptions: Additional opioids should be avoided where possible due to potential for

abuse Regular paracetamol should be tried first line If the patient is still in pain despite this, dihydrocodeine may be used.

Requests for benzodiazepines: Patients prescribed methadone should not be prescribed benzodiazepines

or zopiclone for night sedation (due to the abuse potential associated with these drugs).

Chlordiazepoxide may be used to treat acute alcohol withdrawal owing to the potential seriousness of this syndrome.

The majority of patients admitted will be registered with one of the clinics below or their GP. The clinic should be notified (office hours only) and the prescription suspended at the appropriate community pharmacy to prevent dispensing of duplicate supplies.


Liverpool Drug Dependency Clinic (Hope Street)

0151 709 0516

Brook Place (Tuebrook) 0151 330 8260

Liverpool Drug Rehabilitation Requirement Team (Criminal justice system users)

0151 234 5800

St. Helen’s Lifestyles Team 01744 458364

Addaction (Huyton) 0151 489 3005


Flow Chart for Prescribing Methadone in Patients Admitted for an Unrelated Medical/Surgical Reason


Medicines for Dementia Alzheimer’s disease must be diagnosed in a specialist clinic and treatment may only be initiated by physicians specialising in the care of patients with dementia. For further information see NICE guidance: TA217 Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease

Rivastigmine Symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson's disease. (s) Lead Consultant for Parkinson’s Disease only




ENDOCRINE SYSTEM Contents (Click on heading to go to that section)

Trust Clinical Policy for the Management of Diabetic Keto-acidosis (DKA)

Diagnosis Investigations Management Management of Cerebral Oedema Conversion to Conventional Insulin

Management of Hyperosmolar Hyperglycaemic State (HHS) Diagnosis Treatment

Management of insulin treated diabetic patients and non – insulin treated diabetic patients in the peri-operative period Trust Clinical Policy for Glucose, Potassium and Insulin Infusion (GLIK/Alberti Regimen) for all Patient Groups

Criteria Procedure Blood Glucose Monitoring Plasma Potassium Monitoring

Trust Policy For Intravenous Insulin Therapy Regimen (IVIT)

Suitable Patients Cautions Initiation Adjustment Sodium Requirements Hypoglycaemia

Trust Policy For Intravenous Insulin Therapy Regimen (IVIT) For Diabetic Patients With Renal Impairment (CKD stage 4 and 5 eGFR < 30ml/min) Trust policy for the management of hypoglycaemia

Diagnosis Action Following a Hypoglycaemic Episode

Medicines Used in Diabetes

Insulins Insulin Regimens Oral Antidiabetic Medicines


Diabetes Treatments, Liver & Renal Impairments and selected other cautions Thyroid and Antithyroid Medicines

Thyroid Hormones Antithyroid Medicines

Corticosteroids

Mineralocorticoids Glucocorticoids

Sex Hormones

Female Sex Hormones For Women With a Uterus For Women Without a Uterus

Male Sex Hormones and Antagonists

Anti-Androgens Anabolic Steroids

Hypothalamic and Anterior Pituitary Hormones and Anti–Oestrogens

Anterior Pituitary Hormones Posterior pituitary hormones and antagonists

Medicines Affecting Bone Metabolism

Calcitonin Bisphosphonates

Other Endocrine Medicines

Bromocriptine and Other Dopaminerergic Medicines Medicines Affecting Gonadotrophins Metyrapone Diagnostic Agents for Endocrine Disorders


Trust Clinical Policy for the Management of Diabetic Ketoacidosis (DKA)

Diabetic Keto-Acidosis (DKA) is a potentially life threatening condition. Discuss difficult cases with on-call Specialist Registrar/Consultant. Consider HDU/ITU referral sooner rather than later. Commence treatment immediately if DKA is suspected.

Diagnosis

Laboratory plasma glucose >11 mmol/l (most cases) or known diabetes

Plasma ketones positive AND/OR urine ketones >++.

Arterial pH <7.2 AND/OR plasma Bicarbonate <15 mmol/l.

Blood glucose level >11 mmol/l, urine ketones ++, pH 7.2-7.4 and plasma bicarbonate of 15-20 mmol/l may suggest early DKA

Investigations Urgent:

Laboratory blood glucose and ketones (near patient testing strips e.g. Advantage II; Medisense Precision Plus, are not reliable in the presence of ketones).

Arterial Blood Gases.

U+E’s.

Urine for ketones, glucose, protein,

Blood culture MSU.

U+E and Laboratory Blood Glucose:

Check

every 3 hours for 6 hours,

then

6 hourly for 12 hours,

then

every 12 hours for 1 day,

then daily.


Search for a Cause:

Screen for infection.

Antibiotics are only required in the presence of infection – moderate leucocytosis is a common feature of DKA

Screen for MI in high risk groups.

Consider CVP measurement in cardiac/renal failure.

ECG monitoring in hyper or hypokalaemia.

Urinary catheter if comatose or anuric for >4 hours.

Prophylactic subcutaneous Dalteparin 2500 - 5000 units daily in severely ill patients.

NG tube if persistent vomiting or unconscious.

Plasma expanders in shock.

Management

Fluids Usually 4-8 litres are needed during the first 24 hours

Start IV Sodium Chloride 0.9% as soon as the diagnosis is suspected and adjust infusion rate according to severity of dehydration.

e.g.

1 litre over 1hour, then

1 litre over 2 hours, then

1 litre over 4 hours, then

1 litre every 6-8 hours.

If elderly, in cardiac or renal failure; reduce fluid infusion rate and consider CVP measurement.


Potassium plasma levels usually initially high but concentration falls quickly.

When U&Es available, use premixed IV bags containing potassium as below:

plasma potassium > 5.0 mmol/l

Use Sodium Chloride 0.9% 1 litre without potassium

plasma potassium 3.5 - 5.0 mmol/l

Use Sodium Chloride 0.9% 1 litre + 20 mmol potassium/litre bag

plasma potassium < 3.5 mmol/l

Use Sodium Chloride 0.9% 1 litre + 40 mmol potassium/litre bag.

Insulin Do Not Stop Insulin. Treat any hypoglycaemia as per policy and inform medical staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable control of blood glucose.

Patients on long acting analogue insulins – Insulin Glargine (Lantus) or Insulin Detemir (Levemir) should have them continued whilst they are being treated for DKA.

Use the same starting rate of insulin below whether continuing long acting insulin or not and adjust as per blood glucose

Administer as an intravenous infusion via a syringe driver.

1. Add 50 units of soluble insulin (Humulin S) to 50 mls Sodium Chloride 0.9% (i.e. 1unit/ml).

2. Start at 6 ml/hour (6 units per hour).

3. A fresh solution should be prepared every eight hours for immediate use.

Monitor blood glucose hourly and act on results.

Rapid correction of hyperglycaemia is not advisable.

Aim to decrease blood glucose levels by 5-10% per hour.

After 1 hour, if glucose does not fall by 3-5 mmol/l, increase insulin infusion rate to 12 units/hour.

When blood glucose is <15 mmol/l change IV fluid to 5% Glucose.

Thereafter, aim at maintaining blood glucose at 5 - 12 mmol/l by adjusting insulin infusion rate: (see below)


Blood Glucose <5 mmol/l and not rising:

decrease rate by 0.5 – 1unit / hour to a minimum rate of 0.5 units / hour.

Blood Glucose 5 - 12 mmol/l:

continue at present rate.

Blood Glucose >12 mmol/l and not falling:

increase rate by 0.5 – 1unit / hour.

Bicarbonate

Avoid administration unless pH is < 6.9.

If indicated, give 250 - 500ml of 1.4% sodium bicarbonate over 30 - 60 minutes and assess response.

Management of Cerebral Oedema

Occurs more often in extremes of age especially if hyperglycaemia is rapidly corrected.

Presents with headache, confusion with/without papilloedema.

Investigation

Urgent brain CT scan.

Management

avoid fluid overload.

mannitol by rapid IV infusion - administer (weight (Kg) x 5) ml of 20% solution over 15 minutes

OR

dexamethasone 8.8 mg IV stat then 4.4 mg IM 6 hourly as required for 2-10 days .


Conversion to Conventional Insulin

Patients can eat and drink as soon as they feel able.

Continue IV insulin until acidosis is corrected i.e. 24 hours after clearance of ketonuria and/or plasma bicarbonate >20 mmol/L.

Refer to Specialist Nurse for Diabetes.

If normally on subcutaneous insulin, restart the patient's usual regimen prior to their next meal (e.g. if on insulin analogue give it just before or with the meal or if on other insulins give 30 minutes before their meal) and stop IV insulin 60 minutes later.

If the patient has not had insulin prior to this episode, contact Specialist Registrar for Diabetes for advice.

Management of Hyperosmolar Hyperglycaemic State (HHS) (formerly known as HONK)

HHS is a potentially life threatening condition.

Discuss difficult cases with on-call SpR/Consultant.

Consider HDU/ITU referral sooner rather than later.

Diagnosis

Plasma osmolality (2xNa+ + K] + urea+ blood glucose) >350 mmol/l

Lab glucose >30 mmol/l, no significant ketones or acidosis.

Severe dehydration and hypovolaemia.

Confirm diagnosis, seek cause, full CVS/CNS assessment.

Clinical Investigations

Arterial blood gases

Full blood count

U+E (2 - 4 hourly), glucose, HbA1c, urinalysis (check for urinary ketones also), blood and urine culture, CXR, ECG, coagulation and troponin.


Treatment General

Anticoagulate with treatment dose of Dalteparin (HHS has a high mortality due to thrombotic complications e.g. MI, CVA, PE).

Give broad spectrum antibiotics – Piperacillin/tazobactam 4.5g tds. If penicillin allergic please refer to med micro for advice

Consider need for NG tube, urinary catheter and CVP line.

Fluids

Use Sodium Chloride 0.9% 1litre over 2 hours then 1litre over 4 hours, then 1litre 8 hourly thereafter.

Avoid hypotonic solutions. Give colloid (e.g. gelofusin) if required to raise blood pressure.

Caution ( monitor CVP) in elderly, cardiac or renal disease patients.

If Na+ not declining after 4hrs then consider using hypotonic saline or dextrose with insulin - refer to Diabetes SpR

Potassium Only pre-mixed preparations are available.

Serum potassium>5.0 mmol/l

Use Sodium Chloride 0.9% 1 litre without potassium

Serum potassium 3.5-5.0 mmol/l

Use Sodium Chloride 0.9% with20 mmol potassium chloride, 1 litre bag.

Serum potassium <3.5 Use Sodium Chloride 0.9% with 40 mmol potassium chloride 1 litre bag.

Insulin

Patients on long acting analogue insulins – Insulin Glargine (Lantus) or Insulin Detemir (Levemir ) should have them continued whilst they are being treated for HHS.

Use the same starting rate of insulin below whether continuing long acting

insulin or not and adjust as per blood glucose


Set up a syringe driver with 50 units of soluble insulin Humulin S in 50 mls Sodium Chloride 0.9% (i.e. 1unit/ml )

Start the infusion rate at 2 mls/hr (i.e. 2 units/hr).

The starting rate and incremental increases and decreases will need to be greater in overweight patients with insulin resistance

A fresh insulin solution should be prepared every 8 hours for immediate use.

Monitor BMs hourly and act on your findings aiming to decrease blood glucose no more than 10% per hour. Adjust the insulin infusion rate as follows:

Blood glucose above 12 mmol/l and not decreasing – increase the insulin rate by 0.5 units (0.5 ml) per hour. Blood glucose within target range of 5-12 mmol/l – leave the insulin running at the present rate. Blood glucose below 5 mmol/l and not increasing – decrease the insulin rate by 1 unit (1 ml) per hour to a minimum of 0.5 units (0.5 ml) per hour.

Inform medical staff of hypo or hyperglycaemia or difficulties in achieving stable control of blood glucose.

When patient eating and drinking normally convert back to usual treatment regimen.

If the patient was not previously known to have diabetes refer to the Diabetes SpR for advice.

Management of insulin treated diabetic patients and non – insulin treated diabetic patients in the peri-operative period (Guidelines for anaesthetists and house officers) For type 2 patients on oral hypoglycaemics/ GLP1 ONLY who are well controlled eg have HbA1c <69mmol and there is a short starvation time and morning surgery you should just omit oral hypoglycaemics on the morning of surgery. If afternoon surgery then they can have (as long as they can eat in the morning) metformin as long as no contrast media is involved but oral agents such as long acting sulphonylureas, DPP4 inhibitors and GLP1 should be omitted GKI is needed (see below) if:

The starvation period is longer than 1 meal The patient has poor diabetes control eg HbA1c> 69mmol The patient is on insulin


Guidelines for the management of these patients undergoing elective surgery.

Pre – operative assessment

Note the presence or absence of complications e.g. retinopathy, nephropathy, hypertension, ischaemic heart disease, neuropathy (peripheral and autonomic), foot problems (vascular or neuropathic).

Investigations Urinary protein ECG U & E profile HbA1C

General recommendations

Admit at least 24 to 48 hours prior to surgery. Operation should be in the morning and preferably

not on a Friday. Do not give lactate containing infusions e.g.

Hartmann's Take special care of the heels and malleoli (either side of the ankle joint) in patients with neuropathic feet.

Take the opportunity to assess the patient's skills in injection technique, use of blood glucose monitoring (BM) sticks, use of urine testing sticks etc. and re - educate if problems are identified.

The diagnosis of type 2 diabetes on admission to the surgical ward need not necessitate cancellation of the operation.

Morning of operation Omit breakfast. Omit s.c. insulin if the patient uses insulin.

Check blood glucose and urinalysis at least 1 hour pre - op.

If ketonuria present and/or blood glucose > 17mmol/L, contact anaesthetist. Set up GKI (Alberti) regimen as below. Continue

the GKI regimen until the first post - operative meal. Then restart on full recovery the usual insulin or tablet regimen.

If normally on subcutaneous insulin, restart the patient's usual regimen prior to their next meal (e.g. if on insulin analogue give it just before or with the meal or if on soluble insulins give 30 minutes before their meal) and stop GKI 60 minutes later.

If an afternoon operation is unavoidable, the patient should have a light breakfast, but no s.c. insulin and the GKI infusion should be set up as described below

Diabetic patients undergoing emergency surgery may have special requirements. Please discuss the management with anaesthetists and the diabetes team. When in doubt, ask. The above guidelines are for the management of diabetic patients undergoing elective surgery.


Trust Clinical Policy for Glucose, Potassium and Insulin Infusion (GKI/Alberti Regimen) for all Patient Groups Criteria

If the patient remains NBM after 48 hours consider changing to an intravenous insulin therapy regimen (IVIT).

For surgical patients with renal impairment (plasma creatinine > 150micromol/l) consult the anaesthetist.

Blood glucose must be checked hourly intra-operatively.

Procedure Set up as follows:

Pre-mixed bags of 500 ml of Glucose 10% with 10 mmol potassium

chloride are available. These can be ordered from pharmacy. Stock levels and usage must be recorded in the Controlled Drugs book as this

is an unlicensed product.

1. Add 10 units of soluble insulin Humulin S to the bag and mix well.

2. Run off 50 ml to prevent insulin being adsorbed to the plastic of giving set and start infusion rate at 100 ml/hour.

Patients with Body Mass Index >30:

- consider a higher content of insulin e.g. 16 units.

Patients with Body Mass Index <20, or those who usually require less than 20 units of insulin per day:

- consider a lower content of insulin e.g. 6 - 8 units. NB If patients are on long acting insulin analogue- insulin glargine (Lantus) or insulin detemir (Levemir) then this should be continued and consider halving the number of units of Humulin S that are added to the bag Pre printed orange prescription sheets are available for prescribing GKI

Blood Glucose Monitoring Do not stop insulin. Treat any hypoglycaemia as per policy and inform medical staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable control of blood glucose Check blood glucose hourly and adjust as below

blood glucose <5 mmol/l change infusion bag and reduce insulin content by 4 units.

blood glucose 5-12 mmol/l continue with current infusion bag insulin content.

blood glucose > 12 mmol/l change infusion bag and increase content insulin by 4 units.

Patients requiring larger doses of insulin need larger adjustments of doses e.g. if on a GKI containing 40 units of insulin and BM 14mmol/l, increase insulin by 6-8 units.


Plasma Potassium Monitoring

Check at 4 hours, 8 hours and if stable; every 24 hours Adjust the infusion as follows:

Plasma potassium >5 mmol/l change infusion bag to Glucose 10% without potassium

Plasma potassium 3.5-5 mmol/l continue with current regimen;

Plasma potassium <3.5 mmol/l change infusion bag to Glucose 10% with 20 mmol potassium

(500ml pre-mixed bag).


Trust Policy for Intravenous Insulin Therapy Regimen (IVIT) [For IVIT For diabetic patients with renal impairment (CKD stage 4 and 5 eGFR <30ml/min) click here]

Background Fixed insulin infusion rates for a given blood glucose level, (i.e. sliding scales) produce erratic blood glucose readings and therefore should not be used.

insulin sensitivity varies from patient to patient. Even for a given patient, this

can change during the course of, and recovery from, an illness.

Suitable Patients Those patients who are NBM for a prolonged period e.g. post CVA or have

severe diarrhoea and vomiting etc.

Cautions Patients with renal impairment (CKD stage 4 and 5 eGFR <30ml/min) click

here This regime should not be confused with the ITU Insulin Infusion Protocol

which aims to give very tight blood glucose control in a critical care setting.

Never stop IV insulin in patients with Type 1 diabetes as diabetic ketoacidosis can develop quickly.

Patients on long acting analogue insulins – Insulin Glargine (Lantus) or Insulin Detemir (Levemir ) should have them continued whilst they are on IVIT

Initiation

Determine the appropriate concentration and rate of the glucose (with added potassium) infusion in the clinical circumstances.

1. The concentration and rate of the glucose infusion should be kept constant.

Examples: 5% Glucose containing 20 mmol potassium/litre at 125 ml/hr,

or 10% Glucose containing 40mmol potassium/litre at 62ml/hr

2. Set up a syringe driver with 50 units of soluble insulin Humulin S in 50 mls Sodium Chloride 0.9%, i.e. 1unit per ml.

3. Start the infusion at 2 units (2 mls) per hour. 4. The starting rate and incremental increases and decreases will need to be greater

in overweight patients with insulin resistance; as much as 5 units (5 mls) per hour in some cases.

5. A fresh insulin solution should be prepared every 8 hours for immediate use. 6. Measure and chart blood glucose hourly and act on your findings as below


Adjustment Adjust the insulin infusion rate as follows:

Blood Glucose below 5 mmol/l and not rising

decrease rate by 1 unit (1 ml) per hour to a minimum of 0.5 units (0.5 mls) per hour.

Blood Glucose within target range of 5-12 mmol/l

leave the insulin running at the present rate.

Blood Glucose above 12 mmol/l and not falling

increase the rate by 0.5 units (0.5 mls) per hour.

Sodium Requirements If an IVIT is continued for more than 24 hours, consider adding sodium chloride 0.9% via another line running concurrently with the glucose infusion to avoid hyponatraemia.

Hypoglycaemia

Do Not Stop Insulin. Treat any hypoglycaemia as per policy and inform medical staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable control of blood glucose.


Trust Policy for Intravenous Insulin Therapy Regimen (IVIT) For Diabetic Patients With Renal Impairment (CKD stage 4 and 5 eGFR < 30ml/min) Background Patients with renal impairment may be unable to tolerate the high fluid volumes and potassium load used in Alberti/GKI regimens and the standard IVIT regime used at RLBUHT. The following regimen is recommended for these patients who are undergoing surgery or procedures where the patient will be NBM.

This regime should NOT be confused with the standard IVIT policy or the ITU Insulin Infusion protocol which aims to give very tight blood glucose control in a critical care setting. This is also NOT to be used to treat DKA (Diabetic Ketoacidosis) or HHS (Hyperosmolar Hyperglycaemic Syndrome)

Never stop IV insulin in patients with Type 1 diabetes as diabetic ketoacidosis can develop quickly. Also never have insulin running without glucose infusion running at the same time

Initiation

1. Use 500ml Glucose 10% and run it at 42ml/ hour. No need to routinely add potassium to these bags but if patient is on this regime for > 24hrs please check potassium daily.

2. Set up a syringe driver with 50 units of soluble insulin Humulin S in 50 mls

Sodium Chloride 0.9%, i.e. 1unit per ml. The starting rate is 1 unit (1ml) per hour and adjusted as below.

In overweight patients or patients on high regular insulin doses as much as 5 units (5 mls) per hour may be needed A fresh insulin solution should be prepared every 8 hours for immediate use. Measure and chart blood glucose hourly and act on your findings as below Adjustment of insulin rate Adjust the insulin infusion rate as follows: Blood Glucose below 5 mmol/l and not rising decrease rate by 0.5 units (0.5 ml) per hour to a minimum of 0.5 units (0.5 ml) per hour. Blood Glucose within target range of 5-12 mmol/l leave the insulin running at the present rate. Blood Glucose above 12 mmol/l and not falling increase the rate by 0.5 units (0.5 ml) per hour.


Patients who are NBM for a prolonged period, or those who continue to pass significant volumes of urine may require addition fluids. These patients should be reviewed by a nephrology / transplant consultant or SpR. Hypoglycaemia

Do Not Stop Insulin. Treat any hypoglycaemia as per policy and inform medical staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable control of blood glucose.

For patients who are fluid restricted and nil by mouth give IV 100ml Glucose 20% over 10-15 minutes centrally if possible or via a large vein peripherally to reduce the risk of thrombophlebitis


Trust Policy for the Management of Hypoglycaemia

Diagnosis Capillary blood glucose level below 4 mmol/l. Action For those able to swallow

Give a sugar containing product immediately: e.g. 3 Dextrose tablets ("Dextro energy"® or "Lucozade"®) OR 100 ml of Lucozade® (available from NHS supplies) OR 200 ml of full sugar pop (not diet)

This must be followed immediately by a starch containing food: -

e.g. the patients’ next meal if due or a bowl of plain cereal OR 2 plain biscuits (Digestives) OR a sandwich or 2 pieces of toast.

NB Check blood glucose every 10 minutes until BM ≥ 4mmol/l

For those unable to swallow/ unconscious 200 ml of Glucose 10% IV via peripheral intravenous line over 15-20 minutes For fluid restricted patients give 100 ml of Glucose 20% over 15 minutes,

centrally if possible or via a large vein peripherally to reduce the risk of thrombophlebitis.

OR Glucagon 1 mg sc/im/iv as prescribed. If no response within 10 minutes,

intravenous glucose must be given. NB Check blood glucose every 10 minutes until BM ≥ 4mmol/l

Following a Hypoglycaemic Episode

Insulin and/or oral hypoglycaemic agents must not be omitted; Once the hypoglycaemic episode has been treated as above and blood

glucose is >4 mmol/l, the usual medication should be administered when due. Record all hypoglycaemic episodes and treatment given on the blood glucose

monitoring chart. Try to identify the cause. If recurrent refer to the Diabetes Specialist Nurses for review / advice


.


Medicines Used in Diabetes

Insulins - the main types of insulin preparations available are:

1. Rapid Acting analogue insulins (R) 2. Short acting or Soluble Insulin (S) 3. Intermediate acting or Isophane Insulin (I) 4. Long acting analogue Insulins (L)

Insulin Regimens 1.Basal Bolus

Pre - Breakfast Pre - Lunch Pre - evening meal

Pre - Bedtime

S or R S or R S or R

I or L

2. Twice daily - these are usually fixed biphasic mixtures see below e.g. Humulin M3

Pre - Breakfast Pre - evening meal

S or R S or R

I I

3. Once daily - In patients with type 2 diabetes long acting insulin analogues (e.g. Glargine (Lantus)) can be given once daily with or without oral hypoglycaemic agents


Rapid and Short Acting Insulin

Preparation Species Form Onset (approx.)

Duration of Action (approx.)

Rapid Acting Insulins

Apidra (insulin glulisine)

Analogue Vial Disp pen 3ml cart

10-20 mins 1.5-4 hours

Humalog (insulin lispro*)

Analogue Vial Disp pen, 3ml cart

15 mins 2-5 hours

NovoRapid (insulin aspart)

Analogue Vial Disp pen 3ml cart

10-20 mins 3-5 hours

Short acting insulins

Insuman Rapid Human Disp pen <30 mins 7-9 hours

Humulin S Human Vial 3ml cart

30 mins-1h 6- 12 hours

Intermediate- and Long-Acting Insulins

Preparation Form Onset (approx.)


Intermediate acting insulins

Insulatard Vial, 3ml Cart <1.5 hours 24 hours

Humulin I Vial , 3ml cart Disp pen

30- 60 mins 22 hours

Long-Acting Insulins

Lantus (insulin glargine) Vial 3ml cart Disp pen

2.5 hours 24 hours

Levemir (insulin detemir) 3ml cart, Disp pen

2.5 hours 24 hours


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Biphasic Insulin Preparations Usually given twice daily

Preparation Form Onset (approx.)


Humalog Mix25 3ml cart Disp pen 15 mins 22 hours

Humalog Mix50 Disp pen 15 mins 22 hours

Humulin M3 Vial ,3ml cart, Disp pen

30 mins-1h 22 hours

Insuman Combi 25

Vial, 3ml cart, Disp pen

30mins-1h 12-19 hours

Insuman Combi 50

3ml Cart, Disp pen <30 mins 12-16 hours

NovoMix 30 3ml cart, Disp pen <10-20 mins 24 hours

Vial- 10ml vial Disp pen- Disposable pen device 3ml cart- 3ml cartridge (non disposable pen) Table for insulin preparations adapted from www.emims.net Patients may be admitted on insulin other than those listed above. Please contact pharmacy concerning availability. Contact the Diabetes Specialist Nurse bleep 4041 (RLH) for further advice

Continuous Subcutaneous Insulin Infusion (CSII) (Known as insulin pump therapy) Insulin pumps just require a rapid acting analogue such as Humalog, Novorapid or Apidra. A patient using an insulin pump must be allowed to self manage both their pump and insulin requirements. Dose adjustment for these patients can only be made by a member of the insulin pump management team and named individuals as identified by the team. If glycaemic targets are not achieved or the patient appears too unwell to effectively manage their insulin pump then in the first instance the insulin pump management team should be contacted for advice, if this is not possible then the patient should be converted onto either injection therapy or IV insulin depending on the clinical situation. All patients admitted to hospital who are managed with CSII should be referred via the ICE system for DSN support. For further information please review the hospital policy on insulin pump therapy.


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Oral Antidiabetic Medicines First line

Biguanides

Metformin tablets 500mg once a day gradually increased up to 3 times a day with meals up to a Max 3g daily Alterantively can use 850mg twice daily.

MR tablets. Only to be used in patients unable to tolerate ordinary metformin. More expensive. Initially 500mg once daily increased every 10-15 days, max 2g once daily with evening meal. Renal impairment In patients with a eGFR <45ml/min minute then metformin should be reviewed. NICE 2009 recommends stopping if Serum Cr>150micromol/L or eGFR <30ml/min/1.73m2

Second line

Sulphonylureas

Gliclazide tablets Short acting, choice for elderly and renally impaired. Initially 40 - 80mg daily, adjusted according to response, up to 160mg as a single dose with breakfast. Max. 320mg daily in divided doses. MR tablets: (s) Consultant diabetologists only. Initially 30mg daily with breakfast, adjusted according to response every four weeks. Max 120mg daily NOTE: gliclazide mr 30mg may be considered to be approximately equivalent in therapeutic effect to 80mg of the standard formulation.

Glimepiride tablets Initially 1mg daily adjusted according to response in 1mg steps at 1 - 2 week intervals. Usual max. 4mg (exceptionally, up to 6mg) taken shortly before or with first main meal.



Other Antidiabetic drugs

Pioglitazone tablets

Used alone or in combination with metformin or a sulphonylurea or with both or with insulin. Dose 15 – 30mg once daily increased to 45mg according to response. Important Notes (1) Rosiglitazone has been withdrawn and should be stopped. If it is appropriate you can switch to Pioglitazone, (2) Pioglitazone appears to be associated with an increased risk of bladder cancer which should be taken into consideration when choosing this drug. It should not be used in un-investigated macroscopic haematuria and should be used with care in those at increased risk of bladder cancer. Patients should be monitored at 3-6 months and regularly thereafter

Glitpins

Sitagliptin

For use in patients with type 2 diabetes in combination with metformin or a glitazone or with a sulphonylurea or with metformin and a sulphonylurea To be initiated only by diabetes SpRs and Consultants

GLP-1 Analogues

Exenatide ( injection)

Liraglutide ( injection)

Liraglutide or Exenatide may be useful in some (BMI > 30-35) type 2 patients. Combination with insulin is off-licence and not recommended by NICE Only to be initiated by diabetes SpRs and Consultants Use in combination with metformin or sulphonylurea or both when metformin or sulphonylurea or both inadequate Initially 5 microgram twice daily by s.c. injection. Increased if necessary after at least 1 month to 10 microgram twice daily Use in combination with: – Metformin or a sulphonylurea, in patients with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin or sulphonylurea Or in combination with: – Metformin and a sulphonylurea or metformin and a thiazolidinedione in patients with insufficient glycaemic control despite dual therapy. Initially 0.6mg daily by s.c injection, increased if needed after at least 1 week to 1.2mg daily maximum


Diabetes Treatments, Liver & Renal Impairments and selected other cautions This is not a comprehensive list of cautions & contraindications –for this you must consult the BNF or a pharmacist. We recommend you consult the latest version of the British National Formulary (BNF) or a pharmacist if in doubt. In any patient the decision to use or not to use a treatment is based on a host of factors including a carefully considered risk-benefit analysis agreed with the patient. The table below is a guide: Creat=Serum creatinine in micromole/litre; eGFR=MDRD value; ALT=alanine aminotransferase; ULN=upper limit of normal; CCF=congestive heart failure; Mod LV↓=moderate LV impairment on ECHO or angiography; CK=creatinine kinase; Rx=treatment; and Dose↓=consider dose reduction. Fibrate=fenofibrate. OK=no explicit contraindication or caution.

Adapted from Mersey Health and Community Diabetes guidelines 2011-2013

Thyroid and Antithyroid Medicines

Thyroid Hormones

Levothyroxine sodium (thyroxine) tablets

Initially 50 – 100 micrograms daily, before breakfast, (50 micrograms for those over 50 years). Adjust in steps of 50 micrograms every 3 – 4 weeks until normal metabolism maintained. Usual maintenance dose 100 - 200 micrograms daily. Where cardiac disease is present, 25 micrograms daily OR 50 micrograms on alternate days, adjusted in steps of 25 micrograms. Exclude cortisol deficiency – either clinically or by measuring cortisol as indicated before commencing thyroxine replacement for the first time.

Liothyronine tablets/injection

(s) Consultants only. By mouth: 10 – 20 micrograms daily gradually increased to 60 micrograms daily in 2 - 3 divided doses. By slow i.v injection: hypothyroid coma: 5 – 20 micrograms repeated every 12 hours or more frequently. Alternatively, 50 micrograms initially then 25 micrograms every 8 hours reducing to 25 micrograms daily.

Administration details: Add 2ml water for injection to the ampoule to dissolve powder. Draw up the dose and give as a slow i.v. bolus (over 4 minutes).

`Block and Replace Therapy' for thyrotoxicosis Carbimazole 40mg daily is given for 4 to 6 weeks then when T4 is in normal range ADD levothyroxine sodium [ thyroxine ] 100micrograms daily. Thereafter adjust the levothyroxine sodium [thyroxine] dose to maintain T4 in normal range. Therapy is usually given for 18 months. The `block and replace' regimen has been shown to produce lower relapse rates. It is preferable, because doses do not need to be adjusted once the thyroid tests are in normal range. This regimen should not be used in pregnant women. If Carbimazole is not toletrated consider using Propylthiouracil 200mg bd (need to do LFTs)


Thyrotoxicosis in Pregnancy In pregnant women use propylthiouracil (PTU) if possible. Maximum dose 200mg bd. Wean down rapidly and do monthly Thyroid function tests

Breast feeding-

Propylthiouracil first choice as it crosses the placenta and into breast milk twentyfold less than carbimazole. If the patient is unable to tolerate PTU use the lowest dose carbimazole possible. Patients taking less than 15mg carbimazole or 150mg PTU can safely breastfeed without TFT monitoring of the baby.

Patients should be referred and discussed with Dr Purewal at The Joint Endocrine Disorders of Pregnancy Clinic. Hypothyroidism in pregnancy Thyroid binding globulins increase in pregnancy under hormone stimulation. Patients need more regular TFT monitoring usually 6-8 weekly. Patients should be referred and discussed with Dr Purewal at The Joint Endocrine Disorders of Pregnancy Clinic. Levothyroxine and liothyronine can both be used safely. Thyroid Crisis This is an emergency requiring specialist management. Discuss with an Endocrine Consultant. Please note - Propylthiouracil and Carbamazepine can both cause reversible neutropaenia, and patients should be counselled to stop them and have urgent FBC if they develop a sore throat or high temperature. The drugs are to only be restarted when FBC is shown to be normal.


Antithyroid Medicines CSM warning for Carbimazole Advise patients to report symptoms suggestive of bone marrow depression especially sore throat or mouth ulcers. In such cases treatment should be stopped

Carbimazole tablets For patients not on "block and replace" therapy. Initially, 15 - 40mg daily until the patient becomes euthyroid (usually 4 - 8 weeks). The dose should then be progressively reduced to maintenance of 5 - 15mg daily. Therapy is usually given for 18 months.

Aqueous iodine (Lugol’s) oral solution

(s) Consultants only. Dose: 0.1 - 0.3ml three times daily. Well diluted with milk or water.

Propylthiouracil tablets (s) Consultants only.

Adjuncts to Antithyroid Medicine Therapy

Propranolol tablets Thyrotoxicosis (adjunct): 10 - 40mg 3 - 4 times daily.

Parathyroid Surgery

Methylthioninium Chloride (Methylene Blue) injection

(s) Consultants only. To stain and identify the parathyroid glands. Unlicensed use. Dose: 5mg/Kg body weight in 500mL glucose 5% or Sodium Chloride 0.9% (maximum concentration 350mg in 500ml) over 1 hour. Maximum staining occurs 1 hour after infusion and lasts for about 20minutes.


Corticosteroids All patients receiving long - term therapy should be advised to carry a steroid card.

Mineralocorticoids

Fludrocortisone tablets Mineralo-corticosteroid replacement in adrenocortical insufficiency: 50-300 micrograms daily.

Glucocorticoids

Prednisolone tablets 1mg, 5mg, 25mg

e/c tablets 5mg soluble tablets 5mg

By mouth, initially (depending on condition), 5-20mg daily (severe disease up to 60mg daily) in the morning. Doses may vary depending on a individual basis Note: Enteric coated are not generally recommended and reserved for those patients on doses greater than 60mg.

Dexamethasone tablets/injection

By mouth, usual range 0.5 - 10mg daily. By i.m. or slow i.v. injection, initially 0.5 – 17.6mg daily.

Hydrocortisone tablets/injection

Replacement therapy: By mouth, 10 - 30mg daily in divided doses. Give a higher dose in the morning to mimic diurnal variation e.g. 15mg dose split as 10mg am, 5mg teatime. Some patients do split doses so a 20mg dose may be prescribed as 10mg mane, 5mg midday and 5mg pm Patients should be advised to increase the dose of replacement steroids during periods of stress. By intramuscular, slow i.v. Injection or infusion, 100 - 500mg 3 - 4 times daily.

Methylprednisolone Injection

(s) Consultants only.

Equivalent anti-inflammatory doses of corticosteroids NB This table takes no account of mineralocorticoid effects, nor does it take account of variations in duration of action Prednisolone 5mg equivalent to

Betamethasone 750 micrograms Cortisone acetate 25mg Deflazacort 6mg Dexamethasone 750 micrograms Hydrocortisone 20mg Methylprednisolone 4mg Triamcinolone 4mg


Sex Hormones - See here for agents used in the treatment of malignant disease.

Female Sex Hormones By Consultant prescription only

Oestrogens for Hormone Replacement Therapy Women with a uterus need oestrogen plus progesterone. Women who have

had a hysterectomy require oestrogen only. There is some evidence that transdermal oestrogen is safer than oral oestrogen with reduced risk of venous thromboembolism and gallstones.

For Women with a Uterus - Combined Therapy

1. Sequential Therapy (i.e. Withdrawal Bleeds)

First choice

Estraderm MX 50 patches plus cyclical progesterone

Second choice:

Femoston 1/10 and 2/10,

2. Patients > 1 Year Post–Menopause

Tridestra

3. Continuous Therapy (i.e. No Withdrawal Bleeds)

Tibolone Premique

Low dose oestrogen contains equine derived oestrogens

For Women without a Uterus - Oestrogen Therapy

Estraderm MX patch 25, 50, 75, 100 micrograms

Progynova 1mg, 2mg

Premarin 0.625mg, 1.25mg

Contains equine derived oestrogens

Hormonin

FemSeven patch One patch to be applied weekly.


Progestogens

Norethisterone tablets (s) Consultants only. In conjunction with chemotherapy regimens, the dose used is 5mg tds.

Male Sex Hormones and Antagonists

Testosterone implant/injection


Testosterone patch (Andropatch)


Testosterone gel (s) Consultants only.

Anti-Androgens

Cyproterone tablets (s) Consultants only.

Cyproterone Acetate

Finasteride tablets (s) Urologists only.

Dutasteride capsules (s) Urologists only

Dutasteride and Finasteride

Anabolic Steroids

Nandrolone injection (s) Nephrologists only.

Hypothalamic and Anterior Pituitary Hormones and Anti–Oestrogens

Anterior Pituitary Hormones

Tetracosactride (tetracosactrin) Injection (synacthen test)


Thyrotrophin injection 900mg

(s) Consultants only


Posterior pituitary hormones and antagonists

Desmopressin intranasal spray/tablets/injection


Desmopressin nasal spray/ injection

(Octim)

(s) Consultant Haematologists only

Terlipressin injection (s) Gastroenterologists only.

Vasopressin injection (s) Consultants only.

Antidiuretic Hormone Antagonists

Demeclocycline capsules

(s) Consultants only. Dose: Initially 0.9 – 1.2g daily in divided doses, reduced to 600 – 900mg daily for maintenance. Discontinue if plasma urea rises above the normal range.

Tolvaptan (s) Consultants endocrinologists only. Dose: 15mg once daily for hyponatraemia secondary to SIADH

Medicines Affecting Bone Metabolism

Calcitonin

Calcitonin (salmon) [salcatonin] injection

Prior to starting treatment, give a test dose of 10units sc to exclude hypersensitivity. Hypercalcaemia of malignancy, Calcitonin 100units tid sc for 5 days. For analgesic effect in acute vertebral fracture, Calcitonin 100units sc daily for up to 6 weeks.


Bisphosphonates

Alendronate tablets 70 mg once weekly Prescribers should clearly strike through the days on in-patient prescription charts when doses are not to be taken Must be taken 30 minutes before breakfast with at least a glassful of tap water only. The patient should remain upright for 30 minutes after taking Alendronate.

Risedronate tablets 35mg weekly. See alendronate above for prescribing advice. Pagets disease 30mg: daily for 2 months may be repeated if necessary after at least 2 months Must be taken 30 minutes before breakfast with at least a glassful of tap water only.The patient should remain upright for 30 minutes after taking Risedronate.

Ibandronate 150 mg once a month

Must be taken an hour before breakfast with at least 400ml of tap water only. The patient should remain upright for one hour after taking Ibandronate.

Ibandronate (Bonviva) 3mg IV every three months

For patients with gastrointestinal intolerance to oral bisphosphonates Clinical Biochemistry only

Zoledronate (Aclasta) IV 5mg yearly

For patients with gastrointestinal intolerance to oral bisphosphonates Clinical Biochemistry only

Zoledronate 4mg IV (Zometa)

Paget’s disease of bone. Hypercalcaemia of malignancy. Clinical Biochemistry only

Strontium Ranelate sachets

One 2g sachet daily on an empty stomach eg an hour before breakfast or at least two hours after food.

Other Endocrine Medicines Bromocriptine and Other Dopaminerergic Medicines

Bromocriptine tablets (s) Consultants only.

Cabergoline tablets (s) Consultants only.



Medicines Affecting Gonadotrophins

Danazol capsules (s) Consultants only.

Metyrapone

Metyrapone capsules (s) Consultants only.

Diagnostic Agents for Endocrine Disorders

Corticotropin injection (s) Dermatologists and Gastroenterologists only. Unlicensed.

Protirelin (TRH) injection (unlicensed)


Gonadorelin (LH – RH) injection (unlicensed)


OBSTETRICS, GYNAECOLOGY AND URINARY TRACT DISORDERS

Contents (Click on heading to go to that section) Medicines Used in Obstetrics

Prostaglandins and Oxytocics Common Sexually Transmitted Infections Contraceptives

Emergency Contraception Combined Oral Contraceptives Pregersterone Only Contraceptives

Medicines for Genito-Urinary Disorders

Medicines for Urinary Retention Medicines for Urinary Frequency, Enuresis and Incontinence Medicines Used in Urological Pain Bladder Instillations and Urological Surgery Medicines for Erectile Dysfunction

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Medicines Used in Obstetrics

Prostaglandins and Oxytocics

Oxytocin injection In A & E and theatres.

Ergometrine Injection In A & E and theatres.

Ergometrine with oxytocin injection (Syntometrine)

In theatres.

Common Sexually Transmitted Infections All suspected and confirmed STIs should be referred to GUM / discussed with GUM on call (via switchboard) to enable appropriate investigation, treatment, follow up and partner notification wherever possible. See section 5 (click here) - GENITOURINARY & SEXUALLY TRANSMITTED INFECTIONS

Contraceptives To be prescribed by G.U.M. only.

Emergency Contraception Up to 72 hours after coitus: Levonelle 1500mg (levonorgestrel): 1.5 mg as a single dose as soon as possible

after coitus (preferably within 12 hours but no later than after 72 hours) Between 72 hours and 120 hours after coitus: ellaOne® (ulipristal): 30 mg as a single dose as soon as possible but no later than

after 120 hours

Combined oral contraceptive

e.g. Yasmin, Mercilon, Microgynon Note: The following oral contraceptive preparations should ONLY be prescribed for women intolerant of other combined oral contraceptives and who are prepared to accept an increased risk of thrombosis: Marvelon, Femodene, Femodene ED, Minulet, Triadene, Tri - minulet, Mercilon, Femodette. Progesterone Only Pill - Cerazette Other services available in GUM – long acting reversible contraceptives Implanon insertion / removal IUS (Mirena ) /IUD fitting / removal


http://staffintranet/Library/document_library/departments_and_services/diagnostics_and_therapeutics/Pharmacy/Antimicrobial%20Therapy%202010-11.pdf

Missed Pill Algorithm

Advice for women missing combined oral contraceptives (30-35microgram and 20microgram ethinylestradiol formulations)

If one or two

30-35mcg ethinylestradiol pills have been missed at anytime

OR One 20mcg ethinylestradiol pill is

missed

If three or more

30-35mcg ethinylestradiol pills have been missed at anytime

OR Two or more 20mcg ethinylestradiol

pills are missed

She should take the most recent missed pill as soon as she remembers

She should continue taking the remaining

pills daily at her usual time*

She does not require additional contraceptive protection

She does not require emergency

contraception

She should take the most recent missed as

soon as she remembers

She should continue taking the remaining pills daily at her usual time*

She should be advised to use condoms or

abstain from sex until she has taken pills for 7days in a row

In Addition (because extending the pill-free

interval is risky)

If pills are missed in week 1(Days 1-7)as the pill free interval has been extended

If pills are missed in week 3

(days 15-21) to avoid extending the pill free interval

Emergency Contraception

should be considered if she had unprotected sex in the pill free

interval or in week 1

She should finish the pills in her current pack and start a new pack the next day thus omitting the pill free interval

*Depending on when she remembers her missed pill she may take two pills on the same day

(one at the moment of rememberingand the other at the regular time) or even at the same time


Medicines for Genito-Urinary Disorders A) Medicines for Urinary Retention Acute retention is painful and is managed by catheterisation. Chronic retention is often painless. Alpha Blockers After the cause has been established and treated, medicines may be used to increase detrusor muscle tone. Note: Initiate treatment at night time if postural hypotension is a problem.

1st line Alfuzosin XL Tablets (Alpha 1a selective inhibitor)

2nd line Tamsulosin MR

Tablets/Capsules (Alpha 1a selective inhibitor)

Doxazosin Tablets

Short/Long term use - (s) Urologists only Dosing details: 10mg once daily 2.5mg three times a day (immediate release tablets) – if patient has a stoma / severe diarrhoea Short/Long term use - (s) Urologists only Dosing details: 400micrograms once daily (s) Urologists only For Renal patients with BPH/AUR Dosing details: Initially 1mg once daily, increased according to response to a maximum of 8mg once daily [immediate release tablets should be given in divided doses (twice daily)] Note: Doxazosin has moderate to severe effect on Blood Pressure (Monitor BP)

Note: Anticholinergics may be used for short-term while patients are catheterized to relieve bladder spasms B) Medicines for Benign Prostatic Hyperplasia Alpha Blockers relaxes the smooth muscles of the prostate hence helps free flow of urine through the

prostatic urethra See section above


5-Alpha Reductase Inhibitors (5-ARI) 5-ARI’s inhibits the conversion of testosterone to the more potent Dihydro Testosterone

(DHT) and hence helps to reduce the prostate size in BPH

1st line Finasteride tablets

2nd line Dutasteride tablets (only for patients not suitable for surgery)

(s) Urologists only Dosing details: 5mg once daily (s) Urologists only Dosing details: 500micrograms once daily Note: Pregnant women or women likely to become pregnant must wear hand gloves while handling these tablets Advice patients that children should not handle these tablets

C) Medicines for Transrectal Ultrasound guided Biopsy of Prostate (TRUB) procedure Pre-TRUB: *Ciprofloxacin tablets oral 750mg stat dose (1-hour pre procedure) Gentamicin 3-5mg/kg body weight (up to a maximum dose of 240mg) will be given by

intravenous infusion (in sodium chloride 0.9% 100ml) over 20 minutes – Only for patients allergic to ciprofloxacin (Note: Dose should be prescribed in the TRUB prescription by the doctor in charge of the patient)

Post-TRUB: *At the end of the procedure patients will be administered a stat dose of Metronidazole 1g suppository rectally. For patients allergic to metronidazole, an alternative antibiotic will be administered at the clinician’s discretion (discuss with med-micro). Take home Pre-packs *Ciprofloxacin 500mg every 12hours from the evening of the procedure for 5 doses.

Patients will receive a 10-tablet pack of Ciprofloxacin 250mg with directions to take. *Patients allergic to ciprofloxacin will be discharged with Co-amoxiclav 625mg every

8hours from 8hours post-procedure for 8 doses. Patients receive a 100ml bottle of Co-amoxiclav 250/62.5 suspension with directions to take.

* As per PGD


D) Medicines for Stent removal procedure Ciprofloxacin tablets oral 500mg to 750mg (dependent on size of patient) stat dose (1-

hour pre procedure) Gentamicin 80mg IM for patients below 80Kg and 160mg IM for patients above 80Kg –

Only for patients allergic to ciprofloxacin For patients who have had recent joint replacement (<3 months) or cardiac valve replacement or on immunosuppressants please contact Medical Micro-biology for advise regarding additional Antibiotics cover. Risk will be assessed based on individual patient’s medical history. E) Medicines for Stone Management

Alkalinisation of Urine

Potassium citrate mixture

(s) Urologists only. Dosing details: 10ml three times a day - Take well diluted with water

Sodium Bicarbonate capsules (500mg)

(s) Urologists only. Dosing details: Variable according to individual patient requirements (up to Maximum 10g daily)

Acidification of Urine

Ascorbic acid Tablets

Up to 4g daily in divided doses

Alpha Blockers (Unlicensed use) Alpha blockers relax the smooth muscles of Bladder neck and hence used to help pass stones after fragmentation of stones (used in both male and female)

1st line Alfuzosin XL Tablets

2nd line Tamsulosin MR tablets/capsules

Short term use only - (s) Urologists only Dosing details: 10mg once daily 2.5mg three times a day (immediate release tablets) Short term use only - (s) Urologists only Dosing details: 400micrograms once daily


F) Medicines for Lithotripsy Procedure Pre-Lithotripsy: *Diclofenac suppositories PR 100mg stat dose (or) Diclofenac tablets oral 50mg stat

dose (Maximum daily dose 150mg) *Cyclizine tablets oral 50mg stat dose *Oramorph liquid oral 10 – 20mg or Fentanyl Lozenges 200 – 400micrograms Stat

dose *Ciprofloxacin tablets oral 500mg stat dose *Gentamicin injection Intramuscular 120mg stat dose – Only for patients allergic to

ciprofloxacin Note: 2nd choice anti-emetic Ondansetron Melts 4mg stat dose – to be prescribed by doctor 2nd choice analgesia Alfentanil (RapifenR) IV – dose as required or Pethidine 50mg IM; this is to be prescribed as per CD prescription regulations Post-Lithotripsy: Diclofenac tablets oral 50mg three times a day for 3days Co-codamol tablets oral 8/500 1-2 tablets four times a day for 3 days – Only for

patients allergic to diclofenac Trimethoprim tablets oral 200mg twice daily for 3days – only for patients at moderate

to high risk of UTI (to be prescribed at Doctor’s discretion) Co-amoxiclav tablets oral 375mg three times a day for 3days (for patients allergic to

trimethoprim) – only for patients at moderate to high risk of UTI (to be prescribed at Doctor’s discretion)

Medicines for Urinary Fre quency and Incontinence

Algorithm for use of Anticholinergics in the management of Urinary Frequency & Incontinence

1st Line 2nd Line 3rd Line

Oxybutynin XL tablets 5mg – 20mg once daily Initial dose 5mg, then titrate

Tolterodine XL capsules 4mg once daily

Oxybutynin Patch (9mg/24hrs) 1 patch twice weekly

Solifenacin tablets 5mg – 10mg once daily Initial dose 5mg, then titrate

Trospium SR tablets 60mg once a day

Symptoms uncontrolled with 1st line agents Symptoms uncontrolled with 1st & 2nd line agents

Symptoms controlled but unable to tolerate side-effects

Patients NBM or unable to take oral medicines for longer periods Tolterodine tablets

1mg twice daily (Maximum)

for patients with hepatic impairment or renal impairment (Crcl <30ml/min)


1st Line Oxybutynin immediate-release tablets Oxybutynin XL tablets Oxybutynin (KentaraR) 36mg Patch

For short-term use only Dosing details: 5mg 2 - 3 times daily increased if necessary to maximum 5mg 4 times daily. Elderly 2.5 - 3mg twice daily, increased to 5 mg twice daily according to response and tolerance. For long-term use only - (s) Urologists only Dosing details: Start with 5mg Once daily and titrate according to response up to a Maximum daily dose of 20mg OD Note: Increased risk of side-effects with higher dose especially in elderly patients

Only for the following patient group (s) Urologists only: For patients already stabilised on Oxybutynin tabs but

can’t tolerate the side-effects – trial with the patches and continue if preferred by patient

For patients who can’t take tablets or liquids orally for longer durations

Dosing details: Apply 1 patch twice weekly

1st Line Tolterodine

XL capsules 4mg (DetrusitolR XL)

For short-term or long-term use - (s) Urologists only. Dosing details: 4mg OD Note: For patients with Hepatic impairment or Renal impairment (Crcl <30ml/min) the maximum daily dose must not exceed 1mg twice daily (Use immediate release tablets)

2nd Line Solifenacin Tablets

(VesicareR)

- (s) Urologist only For patients unable to tolerate 1st line agents or whose symptoms persisted with 1st line agents Dosing details: Initial dose 5mg OD, titrated up to a maximum of 10mg OD Note: Increased risk of side-effects with 10mg dose

3rd Line Trospium SR (RegurinR)

tablets

- (s) Urologist only Dosing details: 60mg once a day

Desmopressin (s) Consultant Urologists only.

Amitriptyline or Imipramine

Nocturnal enuresis Dosing details: 10-25mg at night


Analgesics used to relieve Urological Pain

Diclofenac suppositories/injection

Maximum daily dose by any route is 150mg. By rectum, 100mg stat. By deep Intramuscular injection, 75mg into GLUTEAL muscle ONLY. Dose may be repeated after 30 minutes if necessary. Maximum duration of treatment 48 hours (i.e. 4 x 75mg injections).

Pethidine CD injection

By Intramuscular injection, 50 - 100mg.

Lidocaine [lignocaine] 2%,chlorhexidine 0.25% (Instillagel)

To relieve discomfort of catheterisation. Male patients 11mL, female patients 6mL

Oxybutynin To relieve bladder spasms associated with Catheterisation Dose 2.5mg TDS when required (Maximum daily dose 20mg)

Medicines used in Prostate Cancer management Gonadotropin Releasing Hormone (GnRH)/Lutenising Hormone Releasing Hormone (LHRH) Agonists 1st Line Decapeptyl® (Triptorelin) SR 3mg – by Intramuscular injection every 4 weeks Decapeptyl® (Triptorelin) SR 11.25mg – by Intramuscular injection every 3 months Note: Always use 4-weekly injection while initiating on GnRH agonist therapy, then change to 3-monthly injection thereafter. 2nd Line ZoladexR (Goserelin) 3.6mg – by sub-cutaneous injection into anterior abdominal wall every 28 days ZoladexR (Goserelin) LA 10.8mg – by sub-cutaneous injection into anterior abdominal wall every 12 weeks Note: Always use 28-day injection while initiating on GnRH agonist therapy, then change to 12-weekly injection thereafter. Antiandrogens Flare with initial GnRH therapy:

Cyperoterone acetate tablets oral 100mg three times a day (may be reduced to 100mg twice daily) or Bicalutamide tablets oral 50mg once daily Monitoring: LFT’s before initiation of treatment and during treatment

When surgical or other medical intervention (GnRH) inappropriate


Cyperoterone acetate tablets oral 100mg three times a day (may be reduced to 100mg twice daily) or Bicalutamide tablets oral 150mg once daily Monitoring: LFT’s before initiation of treatment and during treatment

Gonadotropin Releasing Hormone (GnRH) Antagonist Degarelix (FirmagonR) MMG have approved the use of degarelix restricted only to those patients in whom LHRH agonist plus a short course of anti-androgen is not suitable (patient’s with risk of spinal cord compression on diagnosis). First dose 240mg (administered as 2 injections of 120mg) subcutaneous into the abdominal region Subsequent doses 80mg subcutaneous into the abdominal region every 28 days

Flow-chart for choice of Gonadotrophin Releasing Hormone (GnRH) agonists / antagonist

Patients diagnosed with Prostate Cancer initiated on Hormonal Treatment

Does Patient have Painful Bony Metastases on Diagnosis?

No Yes

If No Start on GnRH Agonists

If Yes Start on GnRH Antagonists

1st Choice: Triptorelin^ (Decapeptyl®)

2nd Choice: Goserelin ^^ (Zoladex®)

Note: No new patients will be started on Leuprorelin (Prostap®) as from 1st October 2011. The current patients on Leuprorelin will continue to receive it until there treatment is completed.

+ + Cyproterone acetate 100mg BD or 100mg TDS for three weeks

or Bicalutamide 50mg OD for three weeks

Degarelix (Firmagon®) 1st Dose: Cyproterone acetate 100mg BD or

100mg TDS for three weeks or

Bicalutamide 50mg OD for three weeks

240mg as STAT dose by Sub-cutaneous injection From 2nd dose onwards: 80mg by Sub-cutaneous injection every 28 days


Medicines used in Bladder Cancer Management Mitomycin Bladder Instillation 40mg in 40ml Water for Injections (prepared by pharmacy LMCU ext: 3787/3788) (use designated Yellow Mitomycin Cytotoxic prescription chart) Post-TURBT (for suitable patients only):

Stat dose of Mitomycin intravesical instillation 40mg in 40ml Water for Injection should be administered within 6 – 48 hours to get maximum benefit in reducing recurrence Note: Ensure bleeding has stopped post-op before administration of Mitomycin intravesical instillation

Induction regime (administration performed at BGH – Urology Centre)

Induction schedule: Weekly for 6 weeks Dosing details: 40mg in 40ml WFI Shelf-life of the reconstituted solution: 4 days Duration of treatment: 1-hour (to obtain complete covering of the bladder, patients should be advised to stay for 15minutes on each of the following lying positions; Left-side, on stomach, right-side and backside) Route of administration: Intravesical instillation

Maintenance Regime (administration performed at BGH – Urology Centre)

Maintenance regime should be started after the induction regime is completed, and a further 6-week drug free period is observed Maintenance schedule: Monthly thereafter until clinically needed for individual patients Dosing details: 40mg in 40ml WFI Shelf-life of the reconstituted solution: 4 days Duration of treatment: 1-hour (to obtain complete covering of the bladder patients should be advised to stay for 15minutes on each of the following lying positions; Left-side, on stomach, right-side and backside) Route of administration: Intravesical instillation

BCG Bladder Instillation ImmuCystR 81mg (prepared by specialist nurses before administration at BGH-UC) (use designated Green BCG prescription chart) BCG bladder instillation contains live vaccine of BCG hence Must not be administered to patients until after 2 weeks Post-TURBT. Must not be administered to patients with infection, wait until the patient is infection

free for at least 1 week Induction regime (administration performed at BGH – Urology Centre)

Induction schedule: Weekly for 6 weeks Dosing details: 81mg (1.8 – 15.9 x 108 cfu) in sodium chloride 0.9% 50ml


Shelf-life of the reconstituted solution: must be used within 8hours Duration of treatment: 1-hour (to obtain complete covering of the bladder patients should be advised to stay for 15minutes on each of the following lying positions; Left-side, on stomach, right-side and backside) Route of administration: Intravesical instillation

Maintenance Regime (administration performed at BGH – Urology Centre)

Maintenance regime should be started after the induction regime is completed, and a further 6-week drug free period is observed Maintenance schedule: Weeks 1, 2 & 3 at 3months, then weeks 1, 2 & 3 at 6-month intervals (i.e. 6th month, 12th month, 18th month etc.) until clinically needed for individual patients Dosing details: 81mg (1.8 – 15.9 x 108 cfu) in sodium chloride 0.9% 50ml Shelf-life of the reconstituted solution: must be used within 8hours Duration of treatment: 1-hour (to obtain complete covering of the bladder patients should be advised to stay for 15minutes on each of the following lying positions; Left-side, on stomach, right-side and backside) Route of administration: Intravesical instillation


Commonly used Bladder Instillations in Urology

Sodium chloride 0.9% Preferred bladder irrigation for indwelling catheters.

Chlorhexidine gluconate 0.02% (1 in 5,000)

(s) Consultant Urologists only Note: May irritate mucosa and cause burning and haematuria. Discontinue use if this is a problem.

Water, sterile For irrigation

Glycine (s) Urologists only.

DMSO bladder instillation (Prepared by Pharmacy Aseptic Production Unit)

(s) Consultant Urologists only Contains dimethylsulphoxide, hydrocortisone, Sodium bicarbonate and Pentosan polysulphate. Unlicensed preparation for the management of Interstitial Cystitis (IC). (use designated white DMSO prescription chart)

Noxyflex bladder washout

(s) Consultant Urologists only.

Oxybutynin bladder instillation

(s) Consultant Urologists only. Unlicensed preparation (5mg/30ml) for the management of Interstitial Cystitis

Sodium hyaluronidate bladder instillation (CystistatR)

(s) Consultant Urologists Only 40mg in 50ml for the management of Interstitial Cystitis (IC)(use designated white Cystistat prescription chart)

Tranexamic acid bladder instillation

(s) Consultant Urologists Only Unlicensed Preparation (1g in 1000ml) for the management of Refractory Haematuria

Potash Alum 1% bladder instillation

(s) Consultant Urologists Only Unlicensed Preparation (10g in 1000ml) for the management of Refractory Haematuria (Try oral Tranexamic acid and or Tranexamic acid bladder instillation before potash alum is considered) Note: Risk of Aluminium toxicity

Tromethamine (THAM) 7% bladder irrigation

(s) Consultant Urologists Only Unlicensed Preparation (to dissove acetyl cysteine stones, staghorn calculi not dissolved by any other means) – its use is restricted by cost and complexity of the regime. The proposed regime is 60mls per hour for the first 6-7 hours then 30mls per hour continuously for 30 days. The cost per patient for the complete course is approximately £9500 - £18000.


Medicines for Erectile Dysfunction

5-Phosphodiesterase (5-PDE) inhibitors Sildenafil/ tadalafil/Vardenafil


Alprostadil Intracavernosal Injection

CaverjectR, CaverjectR Dual-chamber


Alprostadil Urethral Application MUSER



TREATMENT OF MALIGNANT DISEASE AND IMMUNOSUPPRESSION

Contents (Click on heading to go to that section) Cytotoxic Medicines

Medicines for Chemotherapy induced side – effects Prevention of Urothelial Toxicity

Management of Extravasation Injury Medicines Affecting the Immune Response Antiproliferative Immunosuppressants Corticosteroids and Other Immunosuppressants Other immunomodulating Medicines

Sex Hormones and Antagonists in Malignant Disease

Progestogens Hormone Antagonists Symptom Control in Palliative Care


All items in this section are prescribable by Consultants and Senior Registrars only unless indicated otherwise.

Cytotoxic Medicines Cytotoxic injections are prepared in the Chemotherapy Linda McCartney Centre Unit (Ext. 3787/ 3788/ 3789). Special prescriptions must be used for ordering parenteral cytotoxic regimens (available by contacting the Chemotherapy Unit). Please allow adequate time for preparation of dose/s – 24hrs notice should be given.

Oral Chemotherapy on admission to hospital If oral chemotherapy is continued following admission to hospital patients may receive more than the planned dose of chemotherapy which can lead to serious consequences including death. Moreover patients who are admitted to hospital are likely to be ill and are at greater risk of toxicity and should have the chemotherapy discontinued even if the prescribed course has not been completed. Please take the following action when patients are admitted to hospital on oral chemotherapy: � Merseyside & Cheshire Cancer Network policy is that any oral chemotherapy should be stopped upon admission to hospital. � It should be restarted only after consultation with the relevant specialist. � All patients receiving oral chemotherapy should be in receipt of an alert card which clearly outlines the treatment plan including the duration of any oral chemotherapy treatment. � Patients must be encouraged to carry the card with them and present it to health care professionals. � The MCCN alert card fulfils these requirements. The simple rule is therefore to stop any oral chemotherapy if a patient is admitted to hospital and to seek the advice of the relevant specialist team e.g. Haematology or Acute Oncology If patients are admitted to hospital taking oral anti-cancer medicines for non-cancer indications then a risk assessment must be undertaken and the above guidance applied as appropriate.

NPSA Rapid Response Report 2008_RRR001 Risks of incorrect dosing of oral anti-cancer medicines In January 2009 the National Patient Safety Agency (NPSA) alerted all healthcare staff involved in the use of oral anti-cancer medicines of potentially fatal outcomes if incorrect doses of these medicines are used. These oral anti-cancer medicines are increasingly being used in hospitals and in the community. Risks are increased if non-specialist practitioners prescribe, dispense or administer these oral medicines and bypass the normal safeguards used for injectable anti-cancer medicines. Doctors, nurses, pharmacists and their staff must be made aware that the prescribing, dispensing and administering of oral anti-cancer medicines should be carried out and monitored to the same standard as injected therapy. This requires that:


Healthcare organisations should prepare local policies and procedures that

describe the safe use of these oral medicines. Treatment should be initiated by a cancer specialist. All oral anti-cancer medicines should be prescribed only in the context of a written

protocol and treatment plan. Non-specialists who prescribe or administer on-going oral anti-cancer medication

should have ready access to appropriate written protocols and treatment plans including guidance on monitoring and treatment of toxicity.

Staff dispensing oral anti-cancer medicines should be able to confirm that the prescribed dose is appropriate for the patient, and that the patient is aware of the required monitoring arrangements, by having access to information in the written protocol and treatment plan from the hospital where treatment is initiated and advice from a pharmacist with experience in cancer treatment in that hospital.

Patients should be fully informed and receive verbal and up-to-date written information about their oral anticancer therapy from the initiating hospital. This information should include contact details for specialist advice, which can be shared with non-specialist practitioners. Written information, including details of the intended oral anti-cancer regimen, treatment plan and arrangements for monitoring, taken from the original protocol should be given to the patient. When shared with pharmacists and dispensing staff, this would enable the above dispensing requirements to be satisfied.

Full use should also be made of NHS cancer centre web sites to provide information for healthcare staff, patients and carers to ensure the safe use of oral anti-cancer medicines.

The above guidance is primarily intended to promote the safe use of the medicines listed to treat cancer. Where the use of these medicines is for non-cancer treatment, a risk assessment should be undertaken and the guidance applied as appropriate.


Medicines for Chemotherapy induced side – effects Methotrexate Induced Mucositis and Myelosuppression ("Folate Rescue")

Folinic acid tablets/injection For use with methotrexate. Consult individual treatment protocols for dosage regimes of folinic acid.

Prevention of Urothelial Toxicity

Mesna injection/tablets For use with cyclophosphamide and ifosfamide. Consult individual treatment protocols for dosage regimes of mesna.

Management of Extravasation Injury Stop the infusion and disconnect the drip. Do not remove Cannula. For the management of a suspected extravasation then seek experienced assistance from Senior Haematology Medical, Pharmacy and Nursing staff. Extravasation kits are kept on 7Y, 7YDW and 10Z.

Vinca Alkaloids

NPSA Rapid Response Report 2008_RRR004 Using Vinca Alkaloid Minibags (Adult/Adolescent Units) There have been further reports of fatal and serious incidents from hospitals outside the UK in which doses of vinca alkaloids intended for intravenous administration have been administered by the intrathecal (spinal) route in error. These include three cases where doses of vincristine had been diluted to 10ml and 20ml in syringes. The World Health Organisation (WHO) has issued guidance (see supporting information) recommending that doses of vinca alkaloids should be prepared and administered in intravenous minibags to further minimise the risk of wrong route errors. When vinca alkaloids are prescribed, dispensed or administered in adult and adolescent units:

Doses in syringes should no longer be used. The prescribed dose should be supplied from the hospital pharmacy ready to

administer in a 50ml minibag of sodium chloride 0.9% (for some brands of vinorelbine glucose 5% solution for injection may be used instead of sodium chloride 0.9%).

The following warning should be prominently displayed on the label of ALL vinca alkaloid doses ‘For Intravenous Use Only – Fatal If Administered by Other Routes’.

There should be judicious use of colour and design on the label, outer packaging and delivery bags to further differentiate minibags containing vinca alkaloids from other minibag infusions.

The vinca minibag should be infused intravenously over 5 - 10 minutes and the patient closely monitored for signs of extravasation. Incidents of extravasation should be reported and shared via the National Extravasation Information Service (www.extravasation.org.uk).

Chemotherapy policies and procedures should be amended to reflect these requirements.

Staff should be alerted and trained to follow the new practice. Practice should be audited to ensure compliance with the revised safety procedure.


Intrathecal Chemotherapy The circular HSC 2008/001 covers the updated national guidance on the safe administration of intrathecal chemotherapy and has been implemented across this Trust. For further information contact Senior Haematology Medical and Pharmacy staff.

Merseyside and Cheshire Cancer Network (MCCN) The MCCN was formed in 2000 and links together the organisations that provide care for people with cancer across Merseyside and Cheshire. They work closely with patients, carers, health professionals and managers to help implement the NHS Cancer Reform Strategy and North West Cancer Plan for the people of Merseyside & Cheshire. The Network covers a population of 2.3 million people and encompasses one Strategic Health Authority, seven Primary Care Trusts, twelve Hospital Trusts, ten Hospices and a number of voluntary organisations. The purpose of the Network is broadly to organise and oversee the local implementation of the NHS Cancer Plan which sets out a programme of investment and reform. The Plan also includes a number of ambitious targets with the overall aim to save more lives and to improve the patient’s experience by ensuring that people with cancer have access to the right professional support and access to the best treatment throughout their period of care. Health professionals can access network documents including local and national policies, guidelines, treatment protocols and referral forms through their website (www.mccn.nhs.uk).

Medicines Affecting the Immune Response

Antiproliferative Immunosuppressants

Azathioprine tablets/injection Avoid concurrent use with allopurinol.

Mycophenolate Mofetil capsules/tablets/suspension/injection

Mycophenolate acid e/c tablets (Myfortic)

(s) Consultant Nephrologists only. For patients intolerant of mycophenolate mofetil

Corticosteroids and Other Immunosuppressants

Basiliximab injection (s)Prophylaxis of acute rejection in allogenic renal injection transplantation

Ciclosporin (Sandimmun capsules/liquid/injection or Neoral)

Note: Prescribe by brand name only to avoid confusion between preparations which have different bioavailabilities. All new patients should be commenced on the Neoral brand.

Sirolimus liquid Surgeons. (s) Approved for use by Renal Transplant

Tacrolimus. Capsules (s) Renal transplant Consultant surgeons

Thalidomide tablets (s) Consultant only – refer to the Thalidomide Pharmion Pregnancy Prevention Programme


http://www.mccn.nhs.uk/

Other immunomodulating Medicines

Interferons

Interferon alfa injection (Intron A, Roferon A, Viraferon)

(s) Consultants in Rhematology; and Infectious Diseases and Haematology

Interferon beta (s) Consultant Neurologist use only.

BCG Bladder Instillation

BCG bladder instillation recurrent

Licensed for the treatment of primary or carcinoma and prevention of recurrence following transurethral resection

Sex Hormones and Antagonists in Malignant Disease Progestogens

Megestrol tablets

Medroxyprogesterone tablets

Hormone Antagonists

Breast cancer

Aminoglutethimide tablets

Anastrozole tablets (s) Consultants only.

Formestane injection (s) Consultants only

Fulvestrant injection (s) Consultant breast surgeons only

Letrozole tablets (s) Consultants only.

Tamoxifen tablets

Prostate cancer and gonaderelin analogues

Bicalutamide (s) Urologists only

Buserelin nasal spray

Cyproterone tablets (s) Urologists and Endocrinologists only.

Flutamide tablets/injection (s) Urologists only.

Goserelin injection (s) Urologists only.

Leuprorelin injection (s) Urologists only.


Somatostatin analogues

Octreotide injection See BNF 8.3.4 for range of licensed doses. Unlicensed use: Bleeding oesophageal varices. Administration details: 1mg of octreotide made up to total volume 60ml with sodium chloride 0.9%, the infusion is run at 3ml/hr, i.e. 50micrograms/hour for 20 hours each day (only one infusion a day).

Symptom Control in Palliative Care For advice and support, contact the Palliative Care Team Ext 2274, Bleep 4191.


MEDICINES AFFECTING NUTRITION AND BLOOD Contents (Click on heading to go to that section) Anaemias and Other Blood Disorders

Iron Deficiency Anaemias Medicines used in megaloblastic anaemias Medicines used in hypoplastic, haemolytic and renal anaemias Medicines used in neutropenia

Fluids and Electrolytes

Potassium Management of Hypokalaemia Prevention of Hypokalaemia Established Potassium Depletion SUMMARY OF POTASSIUM CONTAINING INTRAVENOUS INFUSIONS Parenteral Preparations for Fluid and Electrolyte Imbalance

Subcutaneous Administration of Fluids Bicarbonate and lactate

Intravenous Nutrition

Total Parenteral Nutrition (TPN) Oral Nutrition

Enteral Nutrition Minerals

Calcium and magnesium Phosphorus Fluoride Zinc

Vitamins

Vitamin B Group Vitamin C Vitamin D Vitamin E Vitamin K Multivitamins

Metabolic Disorders Medicines for the Treatment of Acute Porphyrias


Anaemias and Other Blood Disorders Iron Deficiency Anaemias Iron preparations can cause altered bowel habit (constipation or diarrhoea) and should be used with care especially in older patients and those with intestinal strictures or diverticular disease. They are best absorbed on an empty stomach but may be given after food to reduce gastro - intestinal side effects, particularly nausea. Timing of dose in relation to other medicines is important as oral iron can reduce the absorption of levothyroxine, alendronate, mycophenolate and some anbibiotics. The absorption of iron is itself reduced by administering with antacids, calcium or zinc preparations. Patients on intravenous iron supplements will not require oral supplements.

Therapeutic Response The haemoglobin concentration should rise by 2g/100ml over 3 - 4 weeks. After the haemoglobin has risen to normal, treatment should be continued for a further three months in an attempt to replenish iron stores. There is no justification for the inclusion of other ingredients, such as vitamins (except folic acid for pregnant women or confirmed folic acid deficiency) with iron in compound preparations.

Modified and Slow Release Iron Preparations These preparations are likely to carry the iron past the area of iron absorption in the gut. The lower incidence of side effects is probably due to the smaller amounts of iron being absorbed. They therefore have no therapeutic advantage over plain preparations.

Oral Iron

Ferrous sulphate 200mg tablets

Therapeutic dose: 200mg 3 times daily (equivalent to 180mg elemental iron daily). Prophylactic dose: 200mg daily (equivalent to 60mg elemental iron daily). Note: There is no liquid preparation of ferrous sulphate available but patients unable to swallow tablets can be converted to another salt (maintain similar daily elemental iron dose)

Ferrous fumarate 140mg/5mL syrup (Fersamal)

10-20mL twice daily (10mL twice daily equivalent to 180mg elemental iron daily) Note: this product requires considerable effort to re-suspend the ferrous fumarate and must be shaken well before dose administration.


Parenteral Iron Preparations For use in patients with proven iron deficiency. Do not start oral iron until 5 days after last

injection. For use when oral therapy unsuccessful due to malabsorption or inability to tolerate oral

iron. Parenteral iron does not produce a faster haemoglobin response than oral iron except in

patients with chronic kidney disease receiving haemodialysis These product carry the risk of anaphylaxis and require test dose administration

Iron Dextran (CosmoFer)injection 50mg/mL

Consult product literature for details of dosage and administration. Consultants use only for total dose infusion.

Iron Sucrose (Venofer) injection 100mg/5ml

Consult product literature for details of dosage and administration. Used for management of anaemia in CKD (see Trust Nephrology policy) I.V. Administration only.

Medicines used in megaloblastic anaemias If megaloblastic anaemia is diagnosed it is essential to establish which deficiency, either vitamin B12 or folate, is present. If there is doubt and where delay may be dangerous then both vitamin B12 and folic acid should be administered. Monitor and treat as for both B12 and folate deficiency. This will prevent precipitation of peripheral neuropathy. Monitor plasma potassium during treatment as hypokalaemia may be precipitated due to an increase in cell turnover when B12 and folic acid are utilised.

Hydroxocobalamin (B12) injection

By i.m. injection, initially, 1mg on alternate days for 1 - 2 weeks. Maintenance, 1mg every 3 months.

Folic acid tablets/liquid 5mg daily. Higher doses up to 15mg may be required in patients with malabsorption.


Medicines used in hypoplastic, haemolytic and renal anaemias

Darbepoietin Injection (Aranesp ®)

(s) Nephrologist use only. Pre-filled syringes

Epoietin beta injection (Neo – Recormon ®)

(s) Nephrologist / Haematologist use only. (To increase yields of autologous blood in predonation programme in moderate anaemia)

Iron Overload

Desferrioxamine injection (s) Consultant use only – seek specialist advice (UK National Poison Service)

Deferasirox tablets (Exjade) (s) Consultant use only – chronic iron overload

Medicines used in neutropenia

Filgrastim (Zarzio) injection (s) Haematologist use only.

Pegfilgrastim (Neulasta) injection

(s) Haematologist use only.

Lenograstim (Granocyte) injection

(s) Haematologist use only.

Fluids and Electrolytes Potassium

Management of Hypokalaemia Compensation for potassium loss is necessary for those patients who: 1) are taking medication which predisposes to hypokalaemia e.g diuretics, especially if co-

prescribed medication such as digoxin or anti - arrhythmic medicines, where potassium depletion may induce arrhythmias

2) have excessive potassium loss e.g. chronic diarrhoea, fistulae.


Prevention of Hypokalaemia Consider dietetic advice regarding potassium - rich food. Compliance with oral potassium salts is often poor due to nausea and vomiting

resulting from inadequate dilution. Therefore, if possible, consider the use of potassium sparing diuretics.

Potassium chloride 25 - 50mmol daily by mouth is suitable for patients taking a normal diet.

Potassium supplements are seldom necessary when low dose diuretics are given for hypertension.

When larger doses of diuretics are used to treat oedema, potassium - sparing diuretics are preferable to chronic administration of potassium salts.

Reduce the dose of potassium supplements in renal failure or the elderly. Established Potassium Depletion

Plasma potassium (2.5 - 3.5mmol/L)

Oral doses of 70 - 100mmol/day may be required over a number of days. It is preferable to give potassium salts as liquid or well diluted soluble tablets rather than slow release preparations, which are large and may cause oesophageal ulceration if not swallowed with plenty of water.

Severe depletion i.e. plasma potassium < 2.5mmol/L

Consider IV therapy using pre-mixed bags of IV fluids containing potassium chloride Peripheral infusion rate not to exceed 10mmol / hour (20mmol/hour by central infusion in critical care setting only where cardiac monitoring available)

Oral Potassium

Potassium chloride effervescent tablets (Sando K)

12mmol potassium per tablet. Two tablets in 200mL water 3 times daily (72mmol/day) until plasma potassium is in required range (usually 3 - 4 days). Do not give at bed - time: risk of oesophageal ulceration.

Potassium chloride syrup 7.5% (1mmol/ml) (Kay - Cee – L)

20mL 3 times daily (60mmol/day) until plasma potassium is in required range. The taste of this product is poorly tolerated by many patients.

Potassium chloride m/r tablets (Slow K)

8mmol potassium per tablet. Two tablets 3 times daily (48mmol/day) until plasma potassium is in required range. Tablets should be swallowed whole with plenty of fluid, during meals whilst standing or sitting up straight. Care is required where patients have oesophageal stricture; hiatus hernia and peptic ulcer disease as could cause ulceration.


Intravenous Potassium The intravenous administration of solutions containing potassium chloride to prevent or correct hypokalaemia is associated with a risk of potentially fatal cardiac effects resulting from the following:

Improper preparation of infusions at ward level using ampoules of very concentrated potassium chloride (e.g. Strong Potassium Chloride injection 15%).

Inadequate mixing of locally prepared infusions resulting in "pockets" of highly concentrated potassium chloride.

(At RLBUHT these risks are reduced following the removal of concentrated potassium chloride/acid phosphate ampoules from all clinical areas. All intravenous potassium is provided as ready mixed infusion bags in various concentrations)

High concentration solutions causing local thrombophlebitis, tissue necrosis and/or loss of IV access.

Excessive rate of infusion. Inappropriately prolonged use of the IV route.

Prior to initiating intravenous therapy, the following require careful consideration: Urgency of potassium replacement, e.g. presence of cardiac arrhythmia, need for

early surgery, very low plasma potassium (<3mmol/L). Co-morbidity (e.g. fluid restriction, renal function) and co-prescription, notably

digoxin or antiarrhythmics. Patient location, i.e. general ward or ITU/POCCU/HDU/CCU. The most appropriate infusion solution in terms of volume and potassium

concentration. The rate of administration and mechanism of rate control (e.g. using IVAC type

infusion pump). The anticipated potassium needs of the patient for the following 24-48 hours. This

should be discussed with a Clinical Biochemist where necessary. Where there remains a clear clinical need for a patient to be treated with intravenous potassium infusions, all staff involved must ensure that this treatment is delivered in a way that minimises all of the known risks and hazards. To this end, the Trust Intravenous Potassium Administration Policy has been prepared.


Trust Intravenous Potassium Administration Policy statements Intravenous treatment of hypokalaemia must only be instigated when the oral/ enteral

route is unavailable or will not achieve the required elevation of plasma potassium within a clinically acceptable time.

All prescribing of potassium must be expressed in terms of millimoles of potassium and must include the rate of infusion and duration of treatment.

A treatment programme considering the patient's potassium needs for the following 24 - 48 hours should be prepared, with assistance from Clinical Biochemisty if necessary.

All ampoules of potassium containing solutions have been removed from, and will not be available to, any ward or clinical area under any circumstances.

Only pre-prepared potassium containing infusions must be used. These are available in the following strengths & presentations: 20mmol in 1000mL of 0.9% sodium chloride or 5% glucose (dextrose) infusion.

(Equivalent to 0.15% potassium chloride) 40mmol in 1000mL of 0.9% sodium chloride or 5% glucose (dextrose) infusion.

(Equivalent to 0.3% potassium chloride) 40mmol in 500mL 0.9% sodium chloride or 5% glucose (dextrose) infusion.

(Equivalent to 0.6% potassium chloride) * 40mmol in 100mL 0.9% sodium chloride infusion. (Equivalent to 3% potassium

chloride) * # * This solution is not commercially available and is purchased as an unlicensed "special" and will be treated as a Controlled Drug within the Trust # This solution is for ITU/POCCU/HDU/CCU use only and must be administered via a central IV line with continuous ECG monitoring of rate & rhythm.

All potassium containing infusions must be administered via a suitable infusion pump to control the infusion rate and volume.

All patients being treated with intravenous potassium are to have at least once daily measurement of plasma potassium until levels are shown to be satisfactory.

Phosphate supplementation: see Section 9

Alberti-GKI. Regimens: see Section 6

The suggested infusion rates according to urgency and degree of hypokalaemia are:

Plasma Potassium level (mmol/L)

Patients with NORMAL Renal Function and NO fluid restriction (Where renal function and/ or fluid intake is compromised, seek senior advice)

Fluid Route Infuse over

Prophylaxis against Hypokalaemia (Normal = 3.5 – 5.3)

20mmol in 1000mL of 0.9% sodium chloride OR 20mmol in 1000mL 5% glucose infusion

peripherally OR Centrally

over at least 8 hours as part of a normal fluids regimen



Plasma Potassium level (mmol/L)

Patients with NORMAL Renal Function and NO fluid restriction (Where renal function and/ or fluid intake is compromised, seek senior advice)

Fluid Route Infuse over

Mild Hypokalaemia (3.0 – 3.4 or non-urgent)

40mmol in 1000mL of 0.9% sodium chloride OR 40mmol in 1000mL 5% glucose infusion

peripherally OR Centrally

over at least 6-8 hours

40mmol in 500mL 0.9% sodium chloride OR 40mmol in 500mL 5% glucose infusion

peripherally OR centrally

over at least 4 hours Severe Hypokalaemia <3 or very urgent

40mmol in 100mL 0.9% sodium chloride infusion administered in ITU/POCCU/HDU/CCU

central line with continuous ECG monitoring of rate & rhythm

over at least 2 hours

Note: Overzealous potassium replacement therapy can result in life threatening hyperkalaemia.

Formula for calculating approximate potassium requirements for replacement:

mmol potassium required = (4 - plasma potassium in mmol) x body weight (kg)

SUMMARY OF POTASSIUM CONTAINING INTRAVENOUS INFUSIONS Millimoles per infusion 'bag'

Intravenous infusion* Na+ K+ Cl- PO43- Order / Supply

Potassium chloride 0.15% in 1000ml glucose 5% 20 20 Stock Requisition / IV 'top-up'

Potassium chloride 0.15% in 1000mL sodium chloride 0.9% 150 20 170 Stock Requisition / IV 'top-up'

Potassium chloride 0.3% in 1000mL glucose 5% 40 40 Stock Requisition / IV 'top-up'

Potassium chloride 0.3% in 1000ml sodium chloride 0.18% and glucose 4%

30 40 30 Stock Requisition / IV ‘top up’

Potassium chloride 0.15% in 1000ml sodium chloride 0.18% and glucose 4%

30 20 30 Stock Requisition / IV ‘top up’

Potassium chloride 0.3% in 1000mL sodium chloride 0.9% 150 40 190 Stock Requisition / IV 'top-up'

Potassium chloride 0.15% in 500 ml glucose 10% (for Gl.I.K. Regimes)

10 10 UNLICENSED CD requisition/ CD register record / CD issue record

Potassium chloride 0.3% in 500 ml glucose 10% (for Gl.I.K. Regimes)

20 20 UNLICENSED CD requisition/ CD register record / CD issue record

Potassium chloride 0.6% in 500ml glucose 5% 40 40 UNLICENSED CD requisition/ CD register record / CD issue record

Potassium chloride 0.6% in 500ml sodium chloride 0.9% 75 40 115 UNLICENSED CD requisition/ CD register record / CD issue record

Potassium chloride 3% in 100ml sodium chloride 15 40 55 UNLICENSED ITU / POCCU/ HDU/CCU use only CD requisition/ CD register record / CD issue record

Potassium Acid Phosphate 1.2% in 250ml (water) 20 20 UNLICENSED

ITU / POCCU/ HDU Others via Clinical Chemistry advice only CD requisition/ CD register record / CD issue record



* The column shows infusion names as they appear printed on the infusion bag label

Summary table notes: Potassium Acid Phosphate 20mmol in 250ml water and potassium chloride 40mmol in 500ml 0.9% sodium chloride may be given peripherally but may cause

thrombophlebitis and loss of venous access. All potassium-containing solutions should be stored in a separate location to other intravenous solutions. Those solutions which require order via CD requisition do not need to be stored in a CD cupboard

Management of Hyperkalaemia

Plasma potassium Action

5.4 - 6.0mmol/L Mild Hyperkalaemia Discontinue any inappropriate prescriptions e.g. potassium sparing diuretics etc.

6.0 - 7.0mmol/L Moderate Hyperkalaemia

No ECG changes: Discontinue any inappropriate prescriptions e.g. potassium sparing diuretics etc. and then By mouth, Calcium Resonium 15g 4 times daily and/or By rectum, Calcium Resonium enema 30g in 100mL administered by bladder syringe and retained for 9 hours. Rectal administration results in more rapid elimination of potassium. Rectal route is appropriate if rapid reduction is required and will act while the calcium resonium by the oral route is in gastro - intestinal transit.

ECG changes: As above plus treatment as for severe hyperkalaemia

> 7mmol/L Severe Hyperkalaemia Discontinue any inappropriate prescriptions e.g. potassium sparing diuretics etc. Urgently seek senior or specialist advice.

With / Without ECG changes:

1) 10mL (equivalent to 6.8mmol of calcium) calcium chloride 10% injection or calcium gluconate to stabilise the myocardium then

2) 10 units of soluble insulin in 250mL bag of glucose 10% given peripherally over 60 to 120 mins.

Fluid restricted patients only: 100mls of 20% glucose with 10 units soluble insulin over 60 - 120mins via syringe driver.

Control potassium levels with calcium resonium orally or rectally.

Monitoring: All patients should have their blood glucose monitored for several hours after the infusion, as the patient may become hypoglycaemic. Consideration may be given to omitting insulin in non - diabetic patients.Monitor calcium in susceptible individuals.

pH < 7.1 Acidotic Seek senior or specialist advice, dialysis may be indicated.

Note: Regularly monitor plasma glucose, potassium and blood pH. The effects of hyperkalaemia recur due to redistribution of potassium in the body.


Oral Sodium Sodium chloride is indicated in states of sodium depletion and usually needs to be given intravenously. Water restriction is effective for dilutional hyponatraemia Only in chronic conditions associated with mild or moderate degrees of sodium depletion are oral supplements indicated. e.g. Renal disease or salt - losing bowel.

Sodium chloride 600mg (s) m/r tablets (Slow Sodium)

Consultants only. 10mmol each of sodium and of chloride. Dose : 4 to 8 tablets daily in divided doses. Take doses with a full glass of water.

Oral Rehydration Salts

Dioralyte sachets Mild to moderate diarrhoea: Reconstitute one sachet with 200mL of water and administer according to fluid loss, usually 200 - 400mL after every loose motion.

Oral Bicarbonate Sodium bicarbonate 500mg

capsules (s) Nephrologists only.

Parenteral Preparations for Fluid and Electrolyte Imbalance Intravenous Sodium Chronic dilutional hyponatraemia should be corrected by water/fluid restriction. Caution: hyponatraemia should be corrected slowly to avoid the risk of osmotic demyelination syndrome. 0.9% sodium chloride can also be used to treat mild to moderate metabolic acidosis. For further information see BNF section 9.2.2: Intravenous sodium.

SODIUM CHLORIDE INTRAVENOUS INFUSIONS

Millimoles per litre Intravenous infusion

Na+ K+ HCO3- Cl- Ca2+

Sodium chloride 0.9% 150 150



Sodium chloride 0.18% and Glucose 4%

30 30


SODIUM CHLORIDE INTRAVENOUS INFUSIONS



Compound sodium lactate (Hartmann's)

131 5 29 111 2

Intravenous Glucose Intravenous glucose 5% is used mainly to replace water deficits and should be given alone when there is no significant loss of electrolytes. e.g. in fevers, hyperthyroidism, diabetes insipidus and hypercalcaemia. Average requirements in a healthy adult are 1.5 - 2.5 litres daily. Sodium chloride and glucose solutions are indicated when there is combined water and sodium depletion. Give in a 1:1 mixture i.e. alternate administration of glucose 5% with sodium chloride 0.9%. Glucose infusions of greater than 10% should be infused via a central i.v. line as they are highly irritant.

Glucose infusions 5%, 10%, 20%, 50%.

Subcutaneous Administration of Fluids When intravenous administration is not possible, large volumes (up to 2 litres per day) of glucose 5% or sodium chloride 0.9% can be given by subcutaneous infusion. Suitable sites for administration include intraclavicular, scapular, abdominal or thigh. Subcutaneous administration is contra – indicated in severe dehydration or shock. Up to 20mmol potassium chloride may be added to each litre of infusion fluid and administered over 3 -4 hours. If the patient experiences discomfort due to the build – up of fluid in the tissues around the administration site, the rate of administration should be reduced. Available evidence suggests that the addition of hyaluronidase to infusion bags for sub - cutaneous administration is NOT necessary in most patients. (S.T. O'Keefe, J.N. Laven, Gerontology1996;42:36-39).


Bicarbonate and lactate

BICARBONATE INTRAVENOUS INFUSIONS



Sodium bicarbonate 8.4% 1000 1000



Sodium bicarbonate is used to control severe metabolic acidosis. Caution:

Intravenous sodium bicarbonate has a high pH. Precipitation may result if it is mixed with any medicines or infusion fluids, (including glucose).

Sodium bicarbonate infusions are likely to cause thrombophlebitis.

Risk of over treatment resulting in alkalosis.

Administer with great care in all situations. Only 1.26% and 1.4% can be infused peripherally.

Seek senior or specialist advice if in doubt.

Sodium bicarbonate 8.4% 10mL, 50ml, 250mL

Plasma Substitutes

Gelofusine infusion

Hydroxyethyl starch 6% in sodium chloride 0.6% (Volulyte 6%)


Intravenous Nutrition Total Parenteral Nutrition (TPN) Caution: Inappropriate administration of PN can have potentially serious consequences. It requires a dedicated intravenous line and meticulous attention to correct aseptic technique. This feeding method is intended for patients when oral / enteral nutrition is not indicated or who cannot achieve adequate nutrition by the oral or enteral route. The duration of parenteral nutrition is determined by the return of gastrointestinal function and may often be 2 weeks or less. For example

Delay in achieving oral/enteral nutritional requirements post-operatively

Mucositis following chemotherapy

Severe pancreatitis where nasojejunal feeding has been unsuccessful

Anastomotic leak

Bowel obstruction

Long-term PN (in some cases Home PN) is needed for patients with prolonged episodes of intestinal failure

Extreme short bowel syndrome of any aetiology

Intestinal fistulae

Gut motility disorders such as scheroderma and chronic idiopathic intestinal pseudo obstruction syndromes

In order for the initiation of TPN to be considered, the patient concerned must be an in - patient on the Royal Liverpool Hospital site. Contacting the Nutrition Team Any patient requiring parenteral nutrition should be referred, to the Nutrition Specialist Nurses or Dietician via the ICE system for a full nutritional assessment. It should be clearly documented in the patients’ case notes why a referral for TPN is being made. Nutrition Team members can be contacted during working hours.

Senior Dietician Bleep 4134

Consultant Nutrition Specialist Nurse

Bleep 4595


Nutrition Nurse Specialist Bleep 4524

Clinical Pharmacist (TPN) (Out of normal hours, contact on-call pharmacist via hospital switchboard)

Bleep 4530

Duty Clinical Biochemist Bleep 4313 (including out of normal hours)

Details which must be available when contacting the Nutrition Team

Patient’s full name

Patient’s unit number

Date of birth

Ward

Consultant

Brief medical details and reason for referral to the Nutrition Team

Other considerations/restrictions e.g. maximum fluid allowance

Once a patient has been assessed as a suitable candidate for parenteral nutrition, the following must be obtained

Current weight of the patient

Biochemistry profile

Sodium, Potassium, Bicarbonate

Urea and Creatinine

Calcium (adjusted) and Phosphate

Magnesium

LFTs (ALP, total Bilirubin, ALT and GGT)

Glucose

Triglycerides

Trace elements (Zinc, Copper and Selenium)

Prealbumin

CRP

Electrolytes may need correction before parenteral nutrition (PN) can be initiated. Full profile electrolyte monitoring will be required on a daily basis until patient is stabilised on PN. Trace elements, prealbumin and triglyceride levels need only be requested once a week


Ward Rounds – Nutrition Team

Members of the Nutrition Team visit new referrals and existing PN patients, (with the exception of ITU) each weekday morning, for assessment; recommendations and monitoring. To avoid duplication of requests and unnecessary phlebotomy, blood sampling request forms remain the responsibility of the patient’s own Consultant team. These routine bloods are required daily during the week unless indicated otherwise by the Nutrition Team.

Manufacture of Parenteral Nutrition (PN) TPN bags are individualised and manufactured each morning using the previous day’s blood results. Stock PN bags are not available. In exceptional cases it may be possible to manufacture a new bag if the initial bag is inappropriate in the light of later results. However the TPN pharmacist must be contacted before 12 noon for any adjustments to the PN regimen. Contact after 12 noon will normally mean that PN will have to be omitted for that day if the bag supplied is considered unsuitable. Discontinuation of PN Wards are contacted by the TPN pharmacist each weekday morning to confirm whether a patient’s TPN regime is running to schedule. This is to avoid the manufacture of excess bags when the schedule is not running to time due to complications e.g. patient pyrexia; administration line problems etc. Each TPN bag can costs up to £100 to produce. Directorates are charged in full for unused bags so please contact TPN pharmacist on bleep 4530 or Aseptic Production Unit on ext 3237 if TPN not required.

PN outside Normal Working Hours – all areas except ITU PN bags cannot be manufactured for patients referred to the Nutrition team after 12 noon on weekdays, or at weekends / Bank Holidays. The Pharmacy Aseptic Unit does not compound PN at weekends, as weekend TPN for patients commenced during the week is manufactured on Friday mornings. Referrals received after 12 noon or at weekends, will be reviewed on the next working day for suitability and appropriate intravenous access. It is not considered an emergency to commence PN out of normal working hours, and can be dangerous if the patient has not been fully assessed. ITU have stock PN with and without electrolytes. These are low volume with high osmolality and unsuitable for peripheral administration. They require separate administration of water soluble vitamins and MUST NOT be requested / supplied for patients outside the critical care setting.


Oral Nutrition Enteral Nutrition Administration of medication via enteral feeding tubes If the oral route is unavailable an alternative medicine or route of administration should be considered (rectal, topical, by subcutaneous or intravenous injection). Only when this is not possible or desired, should medication be administered through an enteral feeding tube. There is a RLUHT nursing protocol for administration of feeds through enteral feeding tubes available on the intranet. This gives information on checking position of tube with pH sensitive paper before each administration of feed or medication, flushing of tubes and other issues around their care. If a patient is unable to receive oral medication and is fed through an enteral feeding tube, the feeding tube can sometimes be used for administration of medicines. Administration of medication via enteral feeding tubes is off label and can cause problems. The bore of nasogastric, nasojejunal and gastrostomy tubes is narrow and medicines can cause blockage of the tube and affect nutritional support. An example of this is acid suppression. Omeprazole MUPS and lansoprazole are both known to cause tube blockage and should be avoided. Suitable alternatives would be ranitidine effervescent tablets or if a PPI is required, esomeprazole is at present the only medicine licensed for gastric tube administration as the tablet can be dispersed in a minimum of 25ml of water. Another problem medicine is ciprofloxacin. The suspension is oil based and will block enteral feeding tubes whereas the tablets are easily dispersed in water. General guidelines suggest the administration of a liquid or a dispersible tablet is least likely to cause tube obstruction. Not all tablets can be safely crushed and dispersed in water. If modified release formulations are crushed they release a high dose of medicine very quickly and the duration of action is reduced. Other controlled release formulations if crushed do not reach the intended site of absorption in the GI tract. Medicine/medicine and medicine/feed interactions are common. This can compromise treatment and is especially important for anti-epileptic medicines e.g. phenytoin and carbamazepine, antibiotics and any medicine with a narrow therapeutic index. For information on prescribing and administering medication through an enteral feeding tube, and advice on appropriate formulations and timing of doses, contact your Ward Pharmacist or Pharmacy Medicines Information Department on extension 2096. Outside of normal pharmacy opening hours you can contact the on-call pharmacist via the duty manager.


Minerals Calcium and magnesium Calcium supplements

Calcium lactate gluconate,

calcium carbonate eff. tablets (Sandocal ®)

Sandocal 400: 10mmol Ca2+/tab. Sandocal 1000: 25mmol Ca2+/tab.

Calcium – Sandoz syrup 2. 2.7mmol Ca2+/5mL.

Cacit effervescent tablets

1.12.6mmol Ca2+/tab. (s) Clinical Chemistry only.

Calcichew tablets 1 12.6mmol Ca2+/tab. (s)

Intravenous calcium may cause arrhythmias; hypotension; nausea and flushing if administered too rapidly.

Calcium gluconate 10% injection

0.22 millimoles Ca2+/mL (1g in 10mL).

Calcium chloride 10% injection

0.68 millimoles Ca2+/mL (1g in 10mL) Injection is hyperosmolar and irritant.

Hypercalcaemia Management

Symptoms of moderate hypercalcaemia:

polyuria, thirst, nausea, vomiting, anorexia, fatigue, constipation.

Symptoms of severe hypercalcaemia:

Confusion, arrhythmia, coma.


Usual range of adjusted calcium: 2.2 – 2.6 mmol/L

Always use adjusted calcium in all dosage calculations.

hypercalcaemia of malignancy is confirmed by:

history

clinical findings

Radilological and histological findings

Suppressed parathyroid hormone (PTH) levels on a blood sample taken prior to any treatment

Commence rehydration with a minimum of 1 – 2 litres sodium chloride 0.9% over 24 hours prior to bisphosphonate therapy followed by a further 1 litre of sodium chloride 0.9% after bisphosphonate therapy, (if possible).

zoledronic acid will normalise adjusted plasma calcium in over 90% of patients (as compared with 75% in pamidronate treated patients).

In some patients, the plasma adjusted calcium will increase above 2.7mmol/L two to

three weeks following initial infusion. A further infusion of 4mg zoledronic acid will normalise the majority of these but in particularly severe hypercalaemia, an 8mg infusion should be considered.

In a small number of patients, the 8mg infusion has been noted to cause renal

impairment.

Cautions:

Ensure adequate hydration.

Monitor serum electrolytes, calcium, phosphate, and magnesium.

Assess renal function before each dose.

Avoid if serum creatinine above 400 micromol/litre

Cardiac disease (avoid fluid overload);

Corticosteroids have not been shown to have any significant clinical benefits in the management of hypercalaemia.

Cinacalcet tablets (s) Consultant Nephrologists only


CORRECTED CALCIUM MMOL/L

ACTION

< 3.0 Asymptomatic: Hydration regimen. Give 3 - 4 litres/day of sodium chloride 0.9% intravenously over 24 hours and repeat calcium measurement. Care with fluid overload and monitor potassium levels. Only give furosemide [frusemide] in presence or anticipation of cardiac failure. Symptomatic: Hydration PLUS

Blood sample for Parathyroid hormone (PTH) BEFORE

zoledronic acid 4mg i.v. in 100mL sodium chloride 0.9% over 15 minutes.

3.0 - 4.0 Hydration as above

PLUS Blood sample for Parathyroid hormone (PTH) BEFORE


> 4.0 Hydration as above

PLUS Blood sample for Parathyroid hormone (PTH) BEFORE


calcitonin (salmon) [salcatonin] 100units s.c. injection 3 times daily may be used to achieve a more rapid control of hypercalcaemia. Give a test dose of 25units to ensure no adverse reactions take place. Repeat plasma calcium after 6 hours. If reduced continue calcitonin (salmon) for 48 hours or until calcium is < 4.0. If calcium is same or increased contact Clinical Chemistry for advice. The effects of calcitonin (salmon) are transient therefore it should be discontinued after 5 days irrespective of plasma calcium measurements.

Notes: sample for parathyroid hormone (PTH) assessment are not required for critical care hypercalcaemia or known lymphoma


Magnesium Causes of magnesium deficiency include excessive losses in diarrhoea, stoma or fistula, alcoholism and diuretic therapy. Supplementation is usually by the intravenous route as magnesium salts are poorly absorbed orally. Use cautiously in renal impairment, (magnesium is renally excreted)

Magnesium glycerophosphate 1g tablets

(s) Unlicensed. Nephrologists only. 4mmol magnesium / 1g tablet. Not suitable for correcting established magnesium deficiency.

Magnaspartate sachets 1 sachet dissolved in 200ml of water provides 10mmol magnesium. Use with caution in diabetics as each sachet contains 3g sucrose.

Magnesium sulphate 50% injection

2mmol magnesium/mL (1g in 2mL). [This schedule is not for treatment of serious arryhthmias including torsades de pointes. See here for details] By i.v. Infusion, Give 10mmol over 12 hours (Maximum 20mmol over 24 hours) in 500mL sodium chloride 0.9%. Administration of larger daily doses than this can exceed the renal threshold causing much of the dose to be excreted. Blood samples for repeat plasma magnesium should be taken several hours after infusion has been completed to allow distribution of magnesium throughout the body. A total of 160mmol over 5 days may be required. Maintenance, usually 12mmol daily.

If intravenous access is restricted and there is hypokalaemia with hypomagnesaemia, magnesium may be added to prepared bags of potassium in saline or glucose. The daily requirement of magnesium should be given in divided doses in each bag of fluid. E.g. If the 24 hour requirement is for two litres of fluid, 12mmol magnesium and 80mmol potassium, prescribe two bags (1 litre) with 6mmol magnesium and 40mmol potassium, each to run over 12 hours


Phosphorus

Phosphate Supplements

Phosphate – Sandoz soluble tablets

Contain 16.1mmol phosphate, 20.4mmol sodium, 3.1mmol potassium. Give up to 100mmol (six tablets) of phosphate

CD Potassium acid phosphate 1.2% in 250ml

20mmol potassium and 20mmol phosphate in 250ml water.

Peripheral administration: 20mmol over 24 hours.

Central venous administration: critical care areas only 20mmol over a minimum of 2 hours.

Sodium phosphate injection

(s) Clinical Chemistry only. as disodium hydrogen phosphate B.P 21.49% 10mL contains 12mmol sodium and 6mmol phosphate

Phosphate Binding Agents

Aluminium hydroxide capsules/suspension (Alucaps / Aludrox)

(s) Nephrologists only.

Calcium acetate 1gram tablets (Phosex)

(s) Nephrologists only calcium 250mg (6.2mmol)

Calcium carbonate tablets (Calcichew, Titralac)

(s) Nephrologists and Clinical Chemistry only.

Lanthanum tablets 500mg and 750mg –Nephrologists - special circumstances only.

Sevelamer capsules (Renagel)

(s) Nephrologists only. For use in patients who develop toxic aluminium levels or in those for whom aluminium hydroxide is ineffective.

Fluoride

Sodium fluoride drops/tablets/rinse/gel

(s) Dental Hospital only.

Zinc

Zinc sulphate125mg soluble tablets (Solvazinc)

(s) 45mg zinc/tablet. Consultants and Dieticians only.


Selenium

Selenium oral solution 100mcg/2ml 6.9 ITU Consultants and Biochemistry only

Vitamins

Vitamin B Group

Thiamine (vitamin B1) tablets

See here for use in alcohol withdrawal.

Vitamin B and C High Potency injection (Pabrinex)

Mix ampoules No.1 and No. 2 in syringe and add to 50mL glucose 5% or sodium chloride 0.9% and give over 20 – 30 mins. For use in management of alcohol withdrawal and once daily for 10 days to minimise refeeding complications in malnourished patients unable to take oral thiamine.

Pyridoxine (vitamin B6) tablets

Deficiency states, 20 - 50mg up to 3 times daily. Prophylaxis for isoniazid neuropathy, 10mg daily.

Nicotinamide tablets (s) Consultants only.

Oral vitamin B complex preparations

Vitamin B Compound Strong tablets

Nicotinamide 20mg, pyridoxine 2mg, riboflavin 2mg, thiamine 5mg/tab Prophylaxis, 1 - 2 tablets daily.

Vitamin C

Ascorbic acid 200mg, 500mg tablets, 1g soluble tablets.

Prophylactic: 25-75mg daily. Low doses can be given as 'Ketovite tablets'– see below for details Therapeutic: not less than 250mg daily in divided doses. Maximum of 1.5g per week in renal patients (i.e. 200mg o.d.)

Ascorbic acid injection (s) Nephrologists only.


Vitamin D

Alfacalcidol capsules/oral liquid

(s) Nephrologists and Consultants only.

Calcitriol capsules/tablets (s) Consultants only.

Calcium and colecalciferol


o Tablet Calcichew D3 – calcium carbonate 1.25g (calcium 500mg or Ca2+ 12.6mmol) colecalciferol 5 micrograms (200 units) Calcichew D3 Forte - calcium carbonate 1.25g (calcium 500mg or Ca2+ 12.6mmol) colecalciferol 10 micrograms (400 units) Adcal D3 Tablets – calcium carbonate 1.5g (calcium 600mg or Ca2+ 15.1mmol), colecalciferol 10 micrograms (400 units).

o Sachet Calfovit D3 – calcium phosphate 3.1g (calcium 1.2g or Ca2+ 30mmol) colecalciferol 20 micrograms (800units)

Calciferol injection Cholecalciferol

Cholecalciferol

(s) Monitor plasma calcium at least once a week. 1000units unlicensed medicine Consultants only 20,000units unlicensed medicine Consultants only

Vitamin E

Vitamin E tablets/suspension


Vitamin K

Menadiol sodium phosphate tablets

Water soluble. Use where fat malabsorption is a problem e.g. biliary obstruction or hepatic disease. Dose: 10mg daily.

Phytomenadione injection By slow i.v. injection - not i.m. See here for oral use of injection in coagulation disorders.

Multivitamins

Multivitamins tablets

Ascorbic acid 15mg, nicotinamide 7.5mg, riboflavin 0.5mg, thiamine 1mg, vitamin A 2500u, vitamin D 300 units. Usual dose: one tablet daily.

Ketovite tablets 1 tablet three times daily for renal patients who need low dose vitamin C Ascorbic acid 16.6mg, riboflavin 1mg, thiamine 1mg, pyridoxine 330mcg, nicotinamide 3.3mg, calcium pantothenate 1.16mg, alfa tocopheneryl 5mg, inositol 50mg, biotin 170mcg, folic acid 250mcg, acetomenaphthone 500mcg.


Metabolic Disorders

Medicines for the Treatment of Acute Porphyrias

Haem arginate injection (s) Consultants only. Contact Medicines Information (Ext. 2096) for administration details.

See current BNF section 9.8.2 for a list of medicines unsafe in Acute Intermittant Porphyria.


MUSCULOSKELETAL AND JOINT DISEASES Contents (Click on heading to go to that section) Medicines Used in Rheumatic Diseases and Gout

Non-Steroidal Anti - Inflammatory Medicines (NSAIDS) Corticosteroids Cytokine Modulators Medicines Which Suppress the Rheumatic Disease Process Gout and Cytotoxic – Induced Hyperuricaemia

Medicines Used in Neuromuscular Disorders Medicines Which Enhance Neuromuscular Transmission Skeletal Muscle Relaxants

Medicines for the Relief of Soft - Tissue Inflammation

Rubefacients and Other Topical Antirheumatics


Medicines Used in Rheumatic Diseases and Gout

Non Steroidal Anti - Inflammatory Medicines (NSAIDS) NSAIDs have an analgesic potency similar to paracetamol when taken on a 'when required' basis. They only exert an anti - inflammatory effect when a regular full dose is given. Differences in anti - inflammatory activity between NSAIDs are small, but there is considerable variation in individual patient response. Therefore it is often necessary to try several analgesic medicines before finding one to suit a particular patient. Most NSAIDs will produce an effect within a few days. The main difference between the NSAIDs is in the side effect profile. All those with a higher incidence of adverse effects are restricted to specialist use only. All NSAIDs cause gastro - intestinal irritation regardless of the route of administration since this side effect is systemic. Therefore e/c and m/r preparations will also cause gastric irritation and possibly bleeding. E/C and m/r preparations are unsuitable for `when required' use. NSAIDs should be used with caution in renal/heart failure.

Aspirin (s) Dermatologists and Gastroenterologists only. Unlicensed.

Ibuprofen tablets/syrup

Ibuprofen m/r tablets (s) Consultants only

Naproxen tablets/suspension/ suppositories

Acute musculoskeletal disorders By mouth, 250 - 500mg twice daily. By rectum, 500mg at night and morning if necessary.

Acute gout: By mouth, 750mg initially then 250mg every 8 hours until attack has passed.

Diclofenac e/c tablets/soluble tablets/suppositories/ injection

Max daily dose by any route is 150mg. By mouth, 25 - 50mg 3 times daily, after food. EC tablets are routinely used

By deep i.m. injection, into GLUTEAL MUSCLE ONLY, 75mg once or twice daily for a max. of 2 days

By i.v. infusion, in appropriately buffered infusion fluid. Contact Medicines Information or refer to BNF for details.

By rectum, 100mg at night. Or every 36 hours if higher dose required.

Ureteric colic: 75mg by i.m. injection into gluteal muscle then a further 75mg after 30 mins if necessary.

Diclofenac s/r tablets (s) Rheumatologists and Orthopaedics only. By mouth, 75mg once or twice daily.

In patients who require long term treatment with NSAIDs who are at risk of developing GI bleeding and ulceration lansoprazole or misoprostol may be used. See gastro-intestinal system section for further recommendations.

Cox-2 inhibitors are only preferable to standard NSAIDs when specifically indicated (eg. particularly high risk of PUD, perforation or bleeding).


In view of evidence of increasing risk of MI, Cox-2 inhibitors are contra-indicated in patients with a history of cardio-vascular disease (including ischaemic heart disease, CVA and TIA). They should be used with caution in high risk groups (↑ BP, ↑cholesterol, diabetic patients and smokers).

Celecoxib (s) Rheumatologists only. By mouth, 100mg twice daily, increased if necessary to maximum 200mg twice daily

Corticosteroids

Local Corticosteroid Injections

Methylprednisolone acetate injection 40mg/ml (Depo-medrone)

By intra-articular or intra-synovial injection 40-80 mg according to patient size.

Hydrocortisone acetate injection 25mg/mL (Hydrocortistab)

By intra-articular or intrasynovial injection, 5 – 10mg according to size of the joint.

Methylprednisolone acetate 40mg, lidocaine [lignocaine] 10mg/mL (Depo-medrone with Lidocaine)

(s) Rheumatologists and Orthopaedics only.

Triamcinolonenacetonide 10mg/mL (Adcortyl)

(s) Intra - articular, intradermal. Dermatologists, Rheumatologists and Orthopaedics only.

Triamcinolone acetonide 40mg/mL (Kenalog)

(s) Intra - articular, intramuscular. Rheumatologists and Orthopaedics only.


Medicines Which Suppress the Rheumatic Disease Process


Sodium aurothiomalate Injection

(s) Rheumatologists only.

Penicillamine Tablets (s) Rheumatologists only.

Hydroxychloroquine tablets

(s) Rheumatologists only.

Methotrexate tablets (s) Consultant only. Usually first line treatment. NB this is a WEEKLY dose Folic acid supplement is required

Methotrexate injection S/C

For patients who have failed to tolerate oral methotrexate NB this is a WEEKLY dose Folic acid supplement is required

Sulphasalazine tablets (s) Rheumatologists only.

Azathioprine (s) Consultants only.

Ciclosporin capsules/liquid/injection

(s) Consultants only. For therapeutic level monitoring see here

Leflunomide tablets (s) Consultant Rheumatologists only. Note: After the washout period, the concentration of active metabolite should be less than 20micrograms/l (measured on 2 occasions 14 days apart) in males or females before conception. Contact Medicines Information for further information.

Note: There are special monitoring requirements with all DMARDs. Contact Rheumatologist or Rheumatology Specialist Nurses for advice and to ensure appropriate monitoring is in place. See British Society for Rheumatology updated guidelines on monitoring requirements for DMARDs. Available at www.rheumatology.org.uk.


http://www.rheumatology.org.uk/

Cytokine Modulators - Consultant use only Adalimumab, Etanercept, Infliximab and Tocilizumab inhibit the activity of tumour necrosis factor. They are indicated for moderate to severe rheumatoid arthritis when the response to DMARDs including methotrexate has been inadequate. Rituximab is indicated when one anti-TNF has failed. See NICE guidance for initiation criteria.

Adalimumab 40mg Injection

(s) Consultant Rheumatologists only. Alternative to etanercept and infliximab. Human monoclonal TNF -antagonist antibody. Given by SC injection every 2 weeks.

Etancercept 25mg injection

(s) Consultant Rheumatologists only Given by SC injection of 25mg twice weekly or 50mg once weekly Also indicated for: Treatment of active polyarticular juvenile chronic arthritis where the response to methotrexate has been inadequate or not tolerated. Treatment of active progressive psoriatic arthritis in adults where response to previous DMARD therapy has been inadequate.

Infliximab 100mg injection

(s) Consultant Rheumatologists, Gastroenterologists. See here for use in Crohn's Disease. IV infusion Administration protocol available from Medicines Information. Should be given with methotrexate

Tocilizumab injection (s) Consultant Rheumatologists only Intravenous infusion every 4 weeks. Dose: 8mg/kg (Max. 800mg)

Rituximab 1g infusion (Prepared by Pharmacy Cytotoxics)

(s) Consultant Rheumatologists only Treatment course: 1g infusion given on day 1 and repeated on day 15. Requires pre-treatment with an anti-pyretic, anti-histamine and corticosteroid. This course may be repeated if necessary every 6 -12 months. Should be given with methotrexate


Gout and Cytotoxic – Induced Hyperuricaemia

Acute Attacks

Naproxen tablets/suspension

750mg initially, then 250mg every 8 hours until the attack has passed.

Colchicine tablets Acute gout: 1mg initially, followed by 500 micrograms every 2 - 3 hours until relief of pain is obtained or vomiting or diarrhoea occurs, or until a total dose of 6mg has been reached. The course should not be repeated within 3 days. Maintenance 1- 2 tablets daily / twice daily. Prevention of attacks during initial treatment with allopurinol: 500micrograms 2 - 3 times daily.

If a patient suffers an acute attack of gout whilst taking allopurinol, the allopurinol should be continued at the same dose throughout the acute attack. If the patient is not already taking allopurinol consider commencing allopurinol 2-3 weeks AFTER the acute attack has subsided.

Long term control Allopurinol should not be started during an acute attack; the initiation may, however, precipitate an acute attack. To prevent this, colchicine or an NSAID should be used as a prophylactic for at least one month after the hyperuricaemia has been corrected (usually about 3 months of prophylaxis). However if an acute attack develops during treatment, then the treatment should continue at the same dosage and the acute attack treated in its own right

Allopurinol tablets Initially, 100mg daily as a single dose, gradually increased over 1 - 3 weeks according to plasma or urinary uric acid concentration. Usual maintenance dose 300mg. Renal impairment, 100mg daily and adjust according to response. Maintenance, 200mg - 600mg daily.

Patients intolerant to allopurinol should be referred to the Rheumatologists for alternative therapy.

Febuxostat tablets (S) Consultant Rheumatologists use only in line with NICE guidance (Click here) Dose: over 18years 80mg once daily, increased to 120mg once daily if uric acid > 6mg/100ml



Medicines Used in Neuromuscular Disorders

Medicines Which Enhance Neuromuscular Transmission

Edrophonium Injection (Tensilon)


Neostigmine tablets/injection


Pyridostigmine tablets (s) Consultants only.

Skeletal Muscle Relaxants

Diazepam tablets/syrup/injection

Muscle spasm of varied aetiology: By mouth, 2 - 15mg daily in divided doses increased if necessary in spastic conditions to 60mg daily according to response. Cost band for 28 days (2mg 3 times daily): B By slow i.v. injection, into a large vein at a rate of not more than 5mg/min. In acute muscle spasm, 10mg repeated if necessary after 4 hours. NB: Only use IM route when oral and IV routes not possible Tetanus: By i.v. injection, 100 - 300 microgram/kg repeated every 1 - 4 hours, by i.v. infusion (or by naso-duodenal tube), 3 - 10mg/kg over 24 hours adjusted according to response.

The following medicines should only be prescribed for the relief of chronic muscle spasm or spasticity; they are not indicated for spasm associated with minor injuries.

Baclofen tablets/liquid 5mg 3 times daily, preferably after food, gradually increased to max. 100mg daily.

Quinine sulphate tablets Nocturnal leg cramps: 200mg at bedtime. Note: If patient is also receiving digoxin, the dose of digoxin should be halved.

Dantrolene capsules (s) Consultants only.


Medicines for the Relief of Soft - Tissue Inflammation

Rubefacients and Other Topical Antirheumatics

Topical NSAIDs

Benzydamine cream (Difflam)

Apply 3 - 6 times daily for up to 10 days.

Piroxicam gel 0.5% Apply 3-4 times daily

Ibuprofen gel 5% Apply 3 times daily

Counter Irritants

PR spray (s) A&E only.


MEDICINES ACTING ON THE EYE Contents (Click on heading to go to that section) Management of Acute Ophthalmic Conditions

General Irrigation Chemical Burns Hypertonic Agents for Clearing Corneal Oedema Systemic Agents

Administration of Medicines to the Eye Control of Microbial Contamination Anti - Infective Eye Preparations Antibacterials

Antifungals Antivirals

Corticosteroids and Other Anti - inflammatory Eye Preparations Corticosteroids Other Anti - inflammatory Preparations

Algorithm for the use of Ozurdex®

Mydriatics and Cycloplegics

Antimuscarinics Sympathomimetics

Treatment of Glaucoma Miotics Sympathomimetics Beta - Blockers Carbonic Anhydrase Inhibitors and Systemic Medicines Prostaglandin Analogues

Local Anaesthetics Miscellaneous Ophthalmic Preparations

Tear Deficiency, Ocular Lubricants and Astringents Prescribing Guideline for Artificial Tears Ocular Diagnostic and Peri-operative Preparations and Photodynamic Treatment Ocular Peri-operative Medicines Ophthalmic Surgery Viscoelastic Polymers Subfoveal Choroidal Neovascularisation ("Age Related Macular Degeneration")

Contact Lenses


All medicines annotated with (s) in this section will be restricted to Ophthalmologists unless otherwise stated. PF = Preservative free.

Management of Acute Ophthalmic Conditions

General Irrigation

Sodium chloride 0.9% 150mL

Chemical Burns

Buffered phosphate eye lotion

(s) For irrigation.

Ascorbic acid plus citrate drops should be used together with the addition of prednisolone 0.5% drops and chloramphenicol 1% ointment for chemical burns according to severity.

Ascorbic acid 10% drops (s) (Potassium ascorbate, Vitamin C)

Citrate 6.5% drops (s) Consultant only

Depending on severity, systemic treatment with ascorbic acid tablets 1g daily and doxycycline capsules 100mg daily can be initiated for the management of chemical burns.

Hypertonic Agents for Clearing Corneal Oedema

Glycerin drops (s) Consultant only

Sodium chloride 5% drops/ointment/PF

(s) Consultant only

Systemic Agents

Glycerol 50% v/v in sodium chloride 0.9% 100mL

(s) To be given orally for the short term reduction of elevated intra-ocular pressure to treat an acute attack of closed angle glaucoma.

Mannitol 20% 500mL Infusion

(s) For intravenous use. Rapid reduction of elevated intra-ocular pressure e.g. acute attack of closed angle glaucoma.


Administration of Medicines to the Eye

Order of Administration of Ophthalmic Preparations When two different ophthalmic preparations need to be administered at the same time of day dilution and over flow may occur. To avoid this, a few minutes should be left between instilling the two different preparations. The order of instillation of drops is also important:

First Miotics (e.g. pilocarpine) and antimuscarinics (e.g. cyclopentolate).

Second Sympathomimetics (e.g. adrenaline/ epinephrine), beta - blockers.

Third Antimicrobials, antivirals.

Fourth Corticosteroids.

Note: Ointments always follow drops. Control of Microbial Contamination Eye drops and ointments should be discarded in line with the instructions or manufacturers leaflet. Eye drops and ointments that have a 4 weeks expiry should be discarded 2 weeks after opening when issued to in - patients except where otherwise indicated. Preservative free eye drops should be stored and discarded in accordance with the manufacturer’s instructions. Anti - Infective Eye Preparations The majority of acute eye infections can be treated topically. Ulcers, keratitis, endophthalmitis are more serious infections and require ophthalmology referral. Subconjunctival injection or systemic administration of antimicrobials may be necessary.


Antibacterials

Conjunctivitis

Chloramphenicol 0.5% drops/minims

Apply up to every two hours then reduce frequency as infection is controlled and continue for 48 hours after healing

Chloramphenicol 1% ointment

Apply either at night (if eye drops used during the day) or 3 - 4 times daily if ointment used alone.

Gentamicin 0.3% drops/minims

Apply up to every 2 hours then reduce frequency as infection is controlled and continue for 48 hours after healing.

Ciprofloxacin 0.3% drops (s) Consultant only

Fusidic acid 1% drops (Fucithalmic)

(s) Consultant only

Chloramphenicol 0.5% PF drops

(s) Consultant only

Chlamydial Conjunctivitis Refer to department of GU medicine for investigation and systemic therapy. Systemic tetracyclines (or erythromycin if tetracycline allergy/intolerance/contraindication) Required

Blepharitis

Chloramphenicol 1% ointment

Apply 3 - 4 times daily.

Fusidic acid 1% drops (Fucithalmic)

(s) Consultant only

Doxycycline capsules 50 – 200mg per day

.


Ulcerative Keratitis Management should be according to protocol, including appropriate and correctly performed sampling.

Ciprofloxacin 0.3% drops (Ciloxan) (s)

Ciprofloxacin 0.3% ointment (Ciloxan) (s)

Teicoplanin 1% drops (s) Prepared by Pharmacy Aseptic Manufacturing

Cefuroxime 5% drops (s) Prepared by Pharmacy Aseptic Manufacturing

Gentamicin 1.4%, 0.3% drops (s)

Other agents as recommended by a microbiologist.

Acanthamoeba Keratitis

Chlorhexidine digluconate 0.02% drops (s)

Propamidine isethionate 0.1% drops (s)

Other Anti - Infective Eye Preparations

Chlortetracycline 1% Ointment (unlicensed) (s)

Framycetin 0.5% drops/ointment (s)

Neomycin 3500units/g ointment (s)

Trimethoprim 0.1% with polymyxin B 10,000 units/mdrops (Polytrim)

(s)

Povidone Iodine eye drops (s) For surgical prophylaxis

Benylpenicillin 20,000units/ml eye drops (s) As recommended by microbiology. Prepared by Pharmacy Aseptic Manufacturing

Vancomycin 5% eye drops (s) As recommended by microbiology. Prepared by Pharmacy Aseptic Manufacturing


Antifungals None commercially available for topical use. Discuss with medical microbiology

Fluconazole 0.2% drops (s) As recommended by microbiology. Prepared by Pharmacy Aseptic Manufacturing

Amphotericin 0.15% & 0.3% eye drops

(s) As recommended by microbiology. Prepared by Pharmacy Aseptic Manufacturing

Voriconazole 1% eye drops (s) As recommended by microbiology. Prepared by Pharmacy Aseptic Manufacturing

Antivirals

Herpetic Eye Disease Sampling for microbiological analysis should usually be performed.

Aciclovir 3% ointment (s) Systemic aciclovir is recommended for certain conditions.

Trifluorothymidine 1% (1% PF) drops

(s)

Intra-ocular Anti - Infective Injections Subconjunctival Injections May be prepared by Pharmacy Aseptic Manufacturing. The optimal volume for sub-conjunctival injections is 0.25mL (prepared with overage).

Cefuroxime 100mg in 0.8mL (s)

Ciprofloxacin 1mg in 0.5mL (s)

Gentamicin 20mg in 0.2mL (s)

Teicoplanin 10mg in 0.25mL (s)

Amphotericin 150 microgram in 0.15mL (s)



Intra-vitreal Injections Prepared by Pharmacy Aseptic Manufacturing. The optimal volume for intra-vitreal injections is 0.1mL. (Prepared with overage to 0.4mL fill volume). The usual regimen for (presumed) bacterial endophthalmitis is:

Ciprofloxacin 0.2mg in 0.1mL (s)

Teicoplanin 1mg in 0.1mL (s)

Others:

Benzylpenicillin 1.2mg in 0.1mL (s)

Cefuroxime 2.5mg in 0.1mL (s)

Gentamicin 0.1mg in 0.1mL (s)

Ganciclovir 2mg in 0.1ml (s)

Foscarnet 2.4mg in 0.1ml (s)


Amphotericin 10microgram in 0.1mL (s)


Prophylaxis against bacterial endophthalmitis in cataract and secondary lens implantation surgery (according to protocol):

Vancomycin 1mg in 0.1mL (s)

Intra-Cameral Injections May be prepared by Pharmacy Aseptic Manufacturing.

Voriconazole 1% (s)

Voriconazole 50 microgram in 0.1ml (s)


Other Intra-ocular Injections

Alteplase (TPA) 25 microgram in 0.1ml (s) May be prepared by Pharmacy Aseptic Manufacturing.



Triamcinolone Injection (Commercially available – off label use)

(s)

Corticosteroids and Other Anti - inflammatory Eye Preparations

Corticosteroids Corticosteroid eye drops must be prescribed by ophthalmologists only. In certain conditions indiscriminate use of topical corticosteroid eye drops may lead to `steroid glaucoma' in predisposed patients. These preparations should be avoided in patients with undiagnosed “red eye”, since this may be due to the herpes simplex virus, and a corticosteroid may aggravate the condition.

General Use

Betamethasone 0.1% drops/ointment (s)

Dexamethasone 0.1% drops (s)

Prednisolone 0.5% (s)

Prednisolone 1% drops (Pred-Forte) (s)

Hydrocortisone ointment 0.5 or 1.0% (Martindale) once or twice daily

(s)

Special Circumstances

Betamethasone Injection (s)

Fluoromethalone 0.1% drops (s)

Prednisolone 0.5% PF (including minims) (s)

Prednisolone 0.03%, 0.05% (preserved) drops

(s)

Prednisolone 0.03%, 0.3%, 1% PF drops (s)


Other Anti - inflammatory Preparations

Antazoline sulphate 0.5% with xylometazoline hydrochloride 0.05%(Otrivine - Antistin) drops

Allergic conjunctivitis: One to two drops 2 - 3 times a day.

Azelastine 0.05% drops (s) C

Emedastine 0.05% drops (s) Consultants and Senior Registrars only.

Nedocromil 2% drops (Rapitil)

(s)

Sodium cromoglicate 2% drops/ PF minims

Allergic conjunctivitis: One to two drops four times a day.

For post - operative inflammation and corneal pain relief:

Diclofenac 0.1% unit dose

(s)

Flurbiprofen 0.03% unit dose

(s)

Ketorolac (Acular) eye drops 0.5% (5mL)

(s)


Algorithm for use of Ozurdex in the treatment of macular oedema in retinal vein occlusion. RVO are classified as ischaemic or non-ischaemic on the basis of clinical appearance, pupillary light response, visual acuity and fluorescein angiography plus further investigations if required, e.g. electrophysiology. Central Retinal Vein Occlusion (CRVO) Non-ischaemic CRVO For patients with visual acuity of between 6/9 and 6/60 due to macular oedema demonstrated by optical coherence tomography (central retinal thickness greater than 250 microns), in the absence of ischaemia as demonstrated by fluorescein angiography, Ozurdex implant is indicated. Patients will be monitored for complications of Ozurdex and therapeutic response. Administration of Ozurdex may be repeated at six months if visual acuity at that juncture is not better than 6/7.5 and central retinal thickness has not been reduced to less than 250 microns. Ischaemic CRVO Management is aimed at treatment of the complications of ischaemia, i.e. rubeosis and rubeotic glaucoma and retinal neovascularisation. It is not intended that ischaemic CRVO be treated with Ozurdex implant. Branch and Hemi-retinal Vein Occlusion (BRVO & H-RVO) Non-ischaemic BRVO or H-RVO For patients with visual acuity of between 6/9 and 6/60 due to macular oedema demonstrated by optical coherence tomography (central retinal thickness greater than 250microns), in the absence of ischaemia as demonstrated by fluorescein angiography Ozurdex implant is indicated. Patients will be monitored for complications of Ozurdex and therapeutic response. Administration of Ozurdex may be repeated at six months if visual acuity at that juncture is not better than 6/7.5 and central retinal thickness has not been reduced to less than 250 microns. Macular grid laser is a therapeutic option in branch retinal vein occlusion. Ischaemic BRVO or H-RVO Management is aimed at treatment of the complications of ischaemia, i.e. vitreous haemorrhage secondary to retinal neovascularisation. It is not intended that ischaemic BRVO/H-RVO be treated with Ozurdex implant. The therapeutic option of intravitreal injections of Bevacizumab remains available for treatment of macular oedema in retinal vein occlusion as an alternative to Ozurdex, for those in whom Ozurdex is contra-indicated and for those in whom Ozurdex is not indicated.


Mydriatics and Cycloplegics Note: Patients should not drive for 1 - 2 hours after mydriasis.

Antimuscarinics

Atropine 0.5% drops 1% drops/ minims/ointment

One or two drops. Duration up to 7 days.

Cyclopentolate 0.5% drops/minims 1% drops/minims

(s) One or two drops. Duration up to 24 hours

Tropicamide 0.5% drops/minims1% drops/minims

(s) Ophthalmologists and A&E only. One or two drops. Rapid action, duration 3 hours.

Sympathomimetics

Phenylephrine 2.5% minims

(s)

Phenylephrine children,10% minims/drops

(s) More toxic than 2.5%, DO NOT use in elderly or patients with cardiovascular disease.


Treatment of Glaucoma

Miotics

Pilocarpine 0.5% drops (s)

Pilocarpine 1%, 2%, 4% drops/minims/3% drops

(s)

Pilocarpine 1%, 2% PF drops (s)

Pilocarpine 4% gel (s)

Sympathomimetics

adrenaline / epinephrine 0.01%, 0.5%, 1% drops

(s) For specific indications only.

Brimonidine 0.2% Drops (Alphagan) (s)

Brimonidine 0.2% & Timolol 0.5%) Drops (Combigan▼)

(s)

Dipivefrine 0.1% Drops (Propine) (s)

Guanethidine (Ganda 1 + 0.2) drops (s) Only for patients previously started.

Beta - Blockers CSM advice: Systemic absorption may follow topical application of eye drops, therefore eye drops containing a beta - blocker are contra - indicated in patients with bradycardia, heart block or heart failure. Beta - blocker eye drops should not be used by patients with asthma or a history of obstructive airways disease unless no alternative treatment is available.

Betaxolol 0.5% drops (Betoptic-S) (s) Patients with respiratory disease.

Carteolol 1%, 2% drops (Teoptic) (s) Restricted usage.

Levobunolol (Betagan) 0.5% drops/unit dose drops

(s) First line.

Timolol 0.25% drops/minims Timoptol LA 0.25% gel Timolol 0.1% gel (Nyogel)

(s) Only for patients already using timolol.


Carbonic Anhydrase Inhibitors and Systemic Medicines

Acetazolamide 250mg s/r capsules (s) First line.

Acetazolamide 250mg tablets (s) Second line.

Acetazolamide 500mg injection (s)

Brinzolamide 10mg/mL drops (Azopt) (s)

Dorzolamide 2% drops (Trusopt) (also available as PF)

(s)

Dorzolamide 2% and Timolol 0.5% (Cosopt) (also available as PF)

(s)

Prostaglandin Analogues

First Line: Latanoprost 0.005% drops (Xalatan) Latanoprost 0.005% & Timolol 0.5%

(Xalacom)

(s)

Second Line: Travoprost (40 mcg/ml) (Travatan) Travoprost 40 mcg/ml & Timolol 0.5%)

(DuoTrav▼) Bimatoprost 0.01% (100mcg /ml) (Lumigan) Bimatoprost 0.03% (300mcg /ml) (Lumigan) Bimatoprost (300mcg /ml & Timolol 0.5%)

(Ganfort▼)

(s)

Local Anaesthetics

Oxybuprocaine 0.4% minims (Benoxinate) (s)

lidocaine [lignocaine] 0.5% minims (with fluoroscein 0.5%)

(s)

Proxymetacaine 0.5% minims (with fluoroscein 0.25%)

(s) first line.

Tetracaine (amethocaine) 0.5% minims (s)


Miscellaneous Ophthalmic Preparations

Tear Deficiency, Ocular Lubricants and Astringents Optimum comfort for artificial tears is achieved when the pH of the product is slightly alkaline at about pH 8.5. Solutions are buffered to maintain the pH using borates, acetates, bicarbonates and phosphates. Most artificial tear preparations are isotonic with normal tears. Dry eye is much less common than thought. It is important that patients fulfil the criteria necessary for the diagnosis of dry eye or tear deficiency. Some patients with mild tear deficiency may be better without artificial tears. Ophthalmologists request that all patients with suspected tear deficiency be referred for an ophthalmic opinion.

Prescribing Guideline for Artificial Tears

KNOWN SENSITIVITY TO PRESERVATIVES

YES

STANDARD 1ST LINE TREATMENTS

1ST LINE PRESERVATIVE-FREE TREATMENTS

DEVELOPS PRESERVATIVE SENSITIVITY

NO

FAILURE TO RESPOND: SECOND LINE TREATMENTS


Drops

FIRST LINE TREATMENTS

WITH PRESERVATIVES WITHOUT PRESERVATIVES

HYPROMELLOSE 0.3%

MINIMS HYPROMELLOSE

LACRILUBE OINTMENT SNOTEARS HYPOTEARS LIQUIFILM

CLINTAS SOOTHE CELLUVISC 0.5% ARTELAC

VISCOTEARS

CELLUVISC 1% VISCOTEARS

SYSTANE

LACRILUBE OINTMENT

SECOND LINE TREATMENTS

HYABAK OPTIVE SYSTANE HYLO-FORTE

Ointments

Lacrilube PF ointment (s)

Simple eye ointment (s)

Gels

Polyacrylic acid Viscotears (PF also) Celluvisc (PF)

(s)


Special Indications

Acetylcysteine 5%, 10% drops (5% PF) (pH 8.5 approx.)

(s)

Hypromellose 2% /1% drops (s)

Hypromellose 0.3% PF drops (s)

Ilube drops (acetylcysteine 5%, hypromellose 0.35%)

(s)

Paraffin liquid drops (s)

Polyvinyl alcohol 1.4%unit dose (s)

Sodium chloride 0.9% drops/minims/PF (s) PF Prepared by Pharmacy Aseptic Manufacturing

Collagen implants ("Shields") (s)

Sno strips (s)

Ocular Diagnostic and Peri-operative Preparations and Photodynamic Treatment

Ocular Diagnostic Preparations

Fluorescein Fluorets (s) Abrasions.

Fluorescein 2% minims (s) Leaks.

Fluorescein 10%/20%/25% injection

(s) Ophthalmic angiography.

Rose bengal 1% minims (s) Diagnostic ocular surface disorders.


Ocular Peri-operative Medicines

Apraclonidine 1% / 0.5% unit dose drops

(s) Prevention of elevated intra-ocular pressure after anterior segment laser surgery.

Diclofenac 0.1% unit dose (s) For post - operative inflammation.

Flurbiprofen 0.03% unit dose (s)

Ketorolac eye drops 0.5%(5mL) (Acular)

(s)

Ophthalmic Surgery

Fluorouracil 5mg/0.2mL injection (s) Trabeculectomy, enhancement. (from cytotoxic unit)

Mitomycin-C 200-400mcg/ml (s) Trabeculectomy enhancement (from pharmacy cytotoxic unit)

Acetylcholine 1% (Miochol) intra-ocular irrigation 2mL

(s) Miosis during surgery.

Balanced salt solution 15mL, 250mL, 500mL

(s) Irrigation during surgery.

Botulinum Toxin (Dysport®) injection 500 units

(s) Blepharospasm, hemifacial spasm,squint, protective ptosis.

Perfluorocarboninjection (s) Retinal detachment surgery not with SPU.

Pefluorohexiloctane injection (s) Alternative to silicone oil and perfluoctane

Silicone oil 1300cst, 5000cst, 5700cst 10mL

(s) Intra-ocular tamponade.

Densiron (s)

Viscoelastic Polymers

Healon (Sodium hyaluronate 0.1%, 1%, 1.4% )

(s)

Viscoat (Sodium chondroitin sulphate 4% & Sodium hyaluronate 3%)

(s)

Enzymes

Hyaluronidase 1500 units injection (s)


Subfoveal Choroidal Neovascularisation ("Age Related Macular Degeneration") Intravenous Injection:

Verteporfin 15mg injection (Visudyne) (s)

Intra-vitreal Injection

Bevacizumab injection (s) Unlicensed - Prepared by Pharmacy Aseptic Manufacturing

Pegaptanib (Macugen) (s)

Ranibizumab (Lucentis▼) (s)

Contact Lenses Where possible, during treatment with eye drops and ointments, contact lenses should

not be worn. This is most important where an infection is present.

Hard lenses are hydrophobic and are therefore not readily penetrated by preservatives or medication. Benzalkonium chloride can be adsorbed onto hard lenses increasing incidence of sensitivity.

Soft lenses are hydrophilic and are prone to absorption and accumulation of medications and preservatives.

Where eye drops are prescribed and continued use of contact lenses is necessary. Preservative free drops should be used wherever possible.

Where preservative free drops are not available lenses should be removed prior to instillation of drops and not replaced for at least 15 minutes.

Benzalkonium chloride is the preservative which causes most sensitivity problems and preparations continuing this product should not be used.

Certain preparations stain soft lenses e.g. dyes (fluorescein and rose bengal). adrenaline (epinephrine) and dipivefrin cause brown/black discoloration. If in doubt, consult an ophthalmologist or the Corneal Specialist Nurse. Administration of eye treatments whilst wearing contact lenses under the supervision of an ophthalmologist, particularly if the contact lens is a bandage contact lens is usually necessary and appropriate.


MEDICINES ACTING ON THE EAR, NOSE AND THROAT Contents (Click on heading to go to that section) Medicines Acting on the Ear

Otitis Externa Removal of Ear Wax

Medicines Acting on the Nose Medicines Used in Nasal Allergy Topical Nasal Decongestants

Medicines Acting on the Oropharynx

Medicines for Oral Ulceration and Inflammation Oropharyngeal Anti - infective Agents Treatment of Dry Mouth


Medicines Acting on the Ear

Otitis Externa Notes 1. Exclude underlying chronic otitis media before commencing treatment. 2. If simple measures such as syringing fail, insert a Tri - adcortyl gauze wick and refer

to aural toilet clinic. 3. If an infection is present, use topical anti - infectives for one week only as prolonged

use may result in fungal infection. Refer if fungal infection is present. (Contact M clinic, ext 2596).

4. The CSM advises that treatment with a topical aminoglycoside antibiotic is contra - indicated in patients who have a perforated ear drum, due to the risk of ototoxicity.

5. An acute infection may require systemic antibiotics.

Astringent Preparations

Aluminium acetate 8% drops (s) ENT only.

Acetic Acid 2% spray (Ear Calm) (s) ENT only.

Anti-inflammatory Preparations

Betamethasone 0.1% drops (s) ENT only.

Anti-infective Preparations

Gentamicin 0.3% drops (s) ENT and A&E only (see notes above).

Ciprofloxacin 0.3% eye drops (s) ENT and A&E only Use Eye Drops – Unlicensed route

Gentamicin tympanic injection (s) ENT Consultants only Unlicensed indication/route

Methylprednisolone tympanic Injection

(s) ENT Consultants only Unlicensed indication/route


Anti–inflammatory Preparations with Antibacterials

Gentamicin 0.3% with Hydrocortisone 1% drops (Gentisone HC)

(s) ENT and A&E only (see notes above)

Neomycin 0.5% with betamethasone 0.1% drops (Betnesol – N)

(s) ENT only

Neomycin 3250units/mL, Dexamethasone 0.1%,glacial acetic acid 2% (Otomize ear spray)

(s) ENT only.

Anti-inflammatory Preparations with Antibacterials and Antifungals

Dexamethasone 0.05% Framycetin 0.5%, Gramicidin 0.005% (Sofradex ) ear drops

(s) ENT only (see notes above).

Removal of Ear Wax Wax may be removed by syringing with warm water. If necessary, wax can be softened with olive oil ear drops before syringing. The patient should lie with the affected ear uppermost for 5 - 10 minutes after a generous amount of the warmed olive oil has been introduced into the ear. If simple remedies fail, sodium bicarbonate ear drops can be used before syringing. Contact M clinic for advice.

Olive oil ear drops Use 1mL oil (warmed to room temp) in the ear 5 - 10mins before syringing.

Sodium bicarbonate 5% drops

Apply 3 - 4 drops twice daily.


Medicines Acting on the Nose

Medicines Used in Nasal Allergy

Antihistamines Oral antihistamines are of value in the treatment of nasal allergies, especially hay fever, and may be of some value in vasomotor rhinitis. They reduce rhinorrhoea and sneezing and may be used in conjunction with systemic nasal decongestants. For more severe symptoms topical nasal decongestants are preferred, plus eye drops (see section above) if necessary.


Topical Nasal Decongestants Corticosteroids

Beclometasone aqueous nasal spray

2 sprays into each nostril twice daily. Max. 8 sprays a day.

Fluticasone nasal spray (Flixonase)

(s) ENT only. 2 sprays into each nostril once daily

Betamethasone 0.1% nose drops

(s) ENT only. 2-3 drops into each nostril 2-3 times a day. Discontinue after 7 days treatment if no response.

Fluticasone Nasal Drops (Flixonase Nasules)

(s) ENT only. 200mcg (approx 6 drops) into each nostril once or twice daily. Discontinue after 7 days treatment if no response.

Sodium chloride 0.9% nasal drops may relieve nasal congestion by helping to liquefy mucous secretions. Other topical nasal decongestants for symptoms associated with vasomotor rhinitis, nasal polyps, and the common cold may be used short term (seven days only). Long term use may give rise to rebound congestion creating a vicious circle.

Sodium chloride 0.9% nasal drops

Instil 1 - 2 drops into each nostril when required.

Xylometazoline 0.1% nasal drops/spray

Instil 2 - 3 drops or 1 spray into each nostril 2 – 3 times daily when required. Max. duration 7 days.

Glucose 25% in glycerine nasal drops

(s) ENT only. Specially manufactured by pharmacy.

Systemic Decongestants Avoid in hypertension, hyperthyroidism, renal failure, diabetes mellitus and glaucoma.

Nasal Staphylococci

Mupirocin 2% nasal ointment (Bactroban)

MRSA eradication:

Chlorhexidine 0.1% and neomycin 0.5% nasal cream (Naseptin)

Eradication of nasal carriage of Staphylococci Apply to nostrils 4 times daily for 10 days. Prevention of nasal carriage of Staphylococci Apply to nostrils twice daily.

Hydrogen peroxide cream 1.5% (Hioxyl)

Prevention of nasal carriage of Staphylococci: Apply to nostrils 2-3 times daily. Microbiologist recommended alternative to Mupirocin and Chlorhexidine/ neomycin products.


Medicines Acting on the Oropharynx

Medicines for Oral Ulceration and Inflammation Ulceration of the oral mucosa may have a number of causes e.g. recurrent aphthae, infections, carcinoma, dermatological disorders, nutritional deficiencies, gastro - intestinal disease, haematopietic disorders, and medicine therapy. It is important to establish the diagnosis in each case, as the majority of lesions require specific management in addition to local treatment. Local treatment aims to protect ulcerated areas, relieve pain or reduce inflammation. Secondary bacterial infection may be a feature of any mucosal ulceration.

Simple Mouthwashes

Mouthwash tablets Dissolve in warm water. To be used at frequent intervals.

Antiseptic Mouthwashes

Chlorhexidine gluconate 0.2%

10mL to be rinsed around the mouth for 1 minute twice daily. Do not swallow in large amounts.

Local Analgesics and Anaesthetics

Choline salicylate oral gel Apply gel with gentle massage up to 3 hourly.

Benzocaine10mg, cetylpyridinium (Merocaine)

One lozenge sucked every 2 hours or as required. Max. 8 lozenges daily.

Benzocaine compound lozenges

One lozenge sucked slowly prior to intubation

Benzydamine oral rinse/spray (Difflam)

Rinse or gargle, using 15mL (dilute with water if stinging occurs), or spray 4 - 8 puffs onto affected area every 2 - 3 hours as required. Do not swallow in large amounts.

Antiseptic Lozenges There is no convincing evidence that antiseptic lozenges have a beneficial effect and they may irritate the oral mucosa causing a sore tongue and lips.

Cetylpyridinium (Merocets)

Use when required.

Mechanical Protection

Carbenoxolone 2% oral gel

Apply after meals and at bedtime.

Carmellose oral paste(Orabase)

Apply a thin layer when necessary after meals.


Local Corticosteroids

Hydrocortisone sodium succinate 2.5mg (Corlan pellets)

Place one lozenge in contact with the ulcer and allow to dissolve slowly. Use 4 times daily after food.

Severe Recurrent Aphthous Ulceration

Chlortetracycline 2% mouthwash

Specially prepared by the Pharmacy. 10mL to be held in the mouth for 2 - 3 minutes 3 times daily for no longer than 3 days. Wait for 3 days (to reduce the incidence of oral thrush) before repeating.

Triamcinolone May be incorporated into the Chlortetracycline mouthwash for more severe cases. At higher doses this mouthwash is given as a substitute for oral steroids and the same systemic side effects may occur. Dose range: 0.25mg - 2mg per 10mL of the mouthwash to be used 3 times daily.

Oropharyngeal Anti - infective Agents

Candidiasis Unopposed candida albicans may cause thrush. This is sometimes precipitated by the use of broad spectrum antibiotics, immunosuppressant medicines or inhaled steroids. If possible withdraw the causative agent. Advise patients to rinse the mouth after inhaled steroid use and to use a spacer device.

Local Treatment ("Artificial Saliva")

Oral Balance Gel For a dry mouth as a result of radiotherapy or sicca syndrome: Apply to gums and tongue as required.

Saliva Orthana spray For a dry mouth as a result of radiotherapy: Spray 2 - 3 times onto oral and pharyngeal mucosa when required. (N.B. porcine derivative).


MEDICINES ACTING ON THE SKIN Contents (Click on heading to go to that section)

Management of skin conditions

Vehicles and Diluents Emollient and Barrier Preparations Topical Local Anaesthetics and Antipruritic Preparations

Topical Corticosteroids Formulation Choice Mild Potency Moderate Potency Potent Very Potent

Preparations for Eczema and Psoriasis Vitamin D and Analogues Coal Tar Preparations Bath preparations


Acne and Rosacea Topical Preparations for Acne Oral Preparations for Acne

Warts and Calluses Sunscreens and Camouflagers Shampoos and Other Preparations for Scalp Conditions

Corticosteroids Coal Tar Other Scalp Preparations

Anti - infective Skin Antibacterial Preparations Antifungal Preparations Antiviral Preparations

Parasiticidal Preparations Preparations for Minor Cuts and Abrasions Skin Cleansers and Antiseptics Antiperspirants


Management of skin conditions All items marked (s) are restricted to dermatologists only. * Denotes items which require individual preparation in pharmacy. These have a limited shelf

life and are more difficult for patients to obtain in the community. # Denotes preparations which may be diluted with a suitable vehicle.

Vehicles and Diluents Aqueous cream Cetomacrogol formula A Emulsifying ointment Hydrous ointment (Oily cream) Lassar's/Hard Lassar's paste Paraffin soft white/yellow Unguentum M

Emollient and Barrier Preparations Aqueous cream

Dermol 500 Lotion

Diprobase cream/ointment

E45 cream

Emulsifying ointment

Epaderm

Hydromol Ointment

Liquid paraffin

Liquid paraffin/WSP 50:50

Oilatum cream

Unguentum M

Preparations Containing Urea

Urea cream 10% (Nutraplus)


Emollient Bath Additives

Balneum bath oil

Balneum Plus bath oil

Emulsiderm bath additive

Oilatum emollient bath oil.

Oilatum Plus emollient

Oilatum shower gel

Barrier Preparations

Cavilon cream

Liquid Paraffin/WSP 50:50 ointment

Topical Local Anaesthetics and Antipruritic Preparations Lidocaine [lignocaine]

5% ointment Apply when required. Max. 35g in 24 hours.

Calamine lotion Apply when required.

Menthol 1% in aqueous cream

Crotamiton cream/lotion (Eurax)

Only for use post scabies treatment.

Topical Corticosteroids Formulation Choice Creams are suitable for moist or weeping lesions whereas ointments are preferable for dry, lichenified or scaly lesions or where a more occlusive effect is required. It is important to reduce strength and frequency of applications as the condition responds.

Mild Potency Hydrocortisone

Hydrocortisone 0.5%, 1% cream/ointment

Apply 2 - 4 times daily.

Hydrocortisone2.5% cream/ointment

(s)

Mildison Lipocream (s)


Compound Preparations

Alphosyl HC cream Coal tar extract 5%, allantoin, hydrocortisone 0.5%.

Canesten HC cream With clotrimazole.

Daktacort cream/ointment (s) With miconazole.

Eurax HC cream (s) With crotamiton.

Fucidin H cream/ointment/gel

(s) With sodium fusidate.

Nystaform HC cream/ointment

(s) With nystatin and chlorhexidine.

Vioform HC cream/ointment

(s) With clioquinol. Stains clothing.

Moderate Potency Alclometasone

Modrasone cream/ointment (s) Cost band for 50g:

Betamethasone Valerate Betnovate RD cream/ointment Apply 2 - 3 times daily.

Clobetasone Butyrate

Eumovate cream/ointment Apply up to 4 times daily.

Trimovate cream (s) With oxytetracycline and nystatin. Stains clothing.

Fluocinolone Acetonide

Synalar 1 in 4 cream/ointment (s) Cost band for 50g cream:

Fludroxycortide [Flurandrenolone]

Haelan cream/ointment/tape (s) Cost band for 60g:

Potent Beclometasone [Beclomethasone] Dipropionate

Propaderm cream/ointment

(s)


Betamethasone Valerate

Betnovate cream/lotion/ointment*#

(s)

Betnovate C cream/ointment

(s With clioquinol.

Betnovate N cream/ointment

(s) With neomycin.

Fucibet cream (s) With fusidic acid.

Betamethasone Dipropionate

Diprosalic ointment (s) With salicylic acid.

Diprosone cream/ointment/lotion

(s)

Lotriderm cream (s) With clotrimazole.

Diflucortolone Valerate

Nerisone cream/ointment/oily cream

(s)

Fluocinolone Acetonide

Synalar cream/ointment (s)

Synalar C cream/ointment

(s) With clioquinol.

Fluocinonide

Metosyn cream/ointment (s)

Hydrocortisone - 17 - Butyrate

Locoid cream/ointment/ lipocream

(s)

Locoid C cream/ointment (s) With chlorquinaldol.

Mometasone Furoate

Elocon cream/ointment*#/lotion

(s) *# in Emulsifying ointment, WSP, LP/WSP


Triamcinolone Acetonide

Nystadermal cream (s) With nystatin.

Very Potent Clobetasol Aropionate

Dermovate cream (s)

Dermovate ointment (s)

Dermovate ointment* (s) (10%,25% or 50%) in white soft paraffin ointment

Clobetasol 0.05%, neomycin 0.5%, nystatin 100,000 IU cream/ointment 30g

(s) (Generic version of Dermovate NN cream/ointment)

Diflucortolone Valerate

Nerisone Forte ointment/oily cream*

(s)

Preparations for Eczema and Psoriasis Preparations for psoriasis Vitamin D and Analogues

Calcipotriol cream/ointment

(s)

Dovobet Ointment (s) Consultant Dermatologists only betamethasone 0.05% (as diproprionate), calcipotriol 50micrograms / g

Silkis Ointment (Calcitriol) for fleural psoriaris

(s)


Coal Tar Preparations Topical Preparations

Alphosyl cream (s) Coal tar extract 5%, allantoin 2%.

Alphosyl HC cream/hydrocortisone

(s) Coal tar extract 5%, allantoin 2%, 0.5

Coal tar solution 5%* in: Betnovate ointment (s)

Coal tar solution (5% or 12%) and salicylic acid (3%)* in:

Eumovate ointment, (s)

Crude coal tar* : (1%, 2%, 5% or 10%) in Yellow Soft Paraffin

Exorex Lotion (s) Coal tar 1%

Bath Preparations Dithranol

Dithranol (0.25%, 0.5%, 1%, 2%, 4% or 8%) and salicylic acid 0.5%* * in:

Emulsifying ointment. (s)

Dithranol (0.1%, 0.25%, 0.5%, 1%, 2%, 4% or 8%) in

Lassar’s paste ointment (s)

Dithranol cream (Dithrocream) 0.1%, 0.25%, 0.5%, 1%, 2%

(s)

Dithranol 0.25% in Haldens emulsifying base

(Dithranol pomade) (s)

Salicylic Acid

Zinc and salicylic acid paste (Lassar's paste)

(s)

Salicylic acid ointment 2%

(s)

Salicylic acid (2%, 5% or 10%)* in:

(s) Emulsifying ointment.

Oral Retinoids for Psoriasis

Acitretin capsules (s) Consultant Dermatologists only. Hospital product only.



Ciclosporin capsules/liquid

(s) Consultant Dermatologists only. Note: Prescribe by brand name (Capimune) as the different preparations have different bio-availabilities. Start all new patients on Capimune.

Mycophenolate 250mg capsules or 500mg tablets

(s) Consultant Dermatologists only. Note: Prescribe by brand name e.g. Myfenax. Start all new patients on Myfenax

Infliximab injection (s) Consultant Dermatologists only

Etanercept injection (s) Consultant Dermatologists only

Ustekinumab Injection (s) Consultant dermatologists only

Methotrexate tablets (s) Consultant Dermatologists only. Note: This is a once weekly dose.

Tacrolimus 0.03%; 0.1% ointment

(s) Consultant Dermatologists only "Protopic"

Pimercrolimus1% (Elidel) Cream

(s) Consultant Dermatologists only

Methoxalen (Psoralens) Preparations for Psoriasis

Methoxypsoralen tablets (s) Unlicensed. Consultant Dermatologists only. 5 - methoxypsoralen and 8 - methoxypsoralen available. Prescriptions must state the brand to be used rather than 5 - or 8 - methoxypsoralen

Acne and Rosacea Topical Preparations for Acne Benzoyl Peroxide and Azelaic Acid

Benzoyl peroxide 2.5,5,10% gel/wash (Panoxyl) (s)

Topical Antibacterials for Acne

Clindamycin topical solution (Dalacin T) (s)

Erythromycin topical solution with zinc (Zineryt) (s)

Topical Retinoids and Related Preparations for Acne

Adapalene 0.1% cream/gel (Differin) (s)

Tretinoin cream/forte cream/lotion/forte gel/gel (Retin A) Isotretinoin gel

(s)


Oral Preparations for Acne Hormone Treatment for Acne

Dianette tablets (s) Consultants only.

Oral Retinoid for Acne

Isotretinoin capsules (s) Consultant Dermatologists only. Hospital only. Roaccutane brand 10mg and 20mg capsules or Beacon brand 5mg and 20mg capsules

Preparations for Warts and Calluses Salactol paint

Salatac gel

Salicylic acid 40% in WSP (s)

Anogenital Warts

Imiquimod cream (s) G.U.M. and Dermatology only

Podophyllotoxin 0.5%topical solution (s) G.U.M. only.

Trichloroacetic acid 50%, 90% (s) G.U.M. only.

Sunscreens Sunscreen Preparations

RoC sunscreen clear/tintedSPF 25 (UVA and UVB)

(s)

Spectraban lotionSPF 25 (UVB) (s)

Spectraban Ultra lotionSPF 28 (UVA and UVB) (s)

Uvistat cream SPF 20, SPF 30, lipscreen SPF 15(UVA and UVB)


Shampoos and Other Preparations for Scalp Conditions Corticosteroids

Betnovate (Betamethasone valerate)

(s)

Dermovate(Clobetasol) (s)

Diprosalic (Betamethasone, salicylic acid)

(s)

Diprosone(Betamethasone dipropionate

(s)

Elocon(Mometasone furoate)

(s)

Coal Tar

Alphosyl shampoo/ 2 in 1 shampoo

(s) Alcoholic coal tar extract 5%.

Capasal shampoo Coal tar 1%, coconut oil 1% salicylic acid 0.5%.

Cocois ointment Cost band for 100g: C

Coconut compound ointment

(s)

Polytar/Polytar plus shampoo

(s)

SCC sal/SCC sal (scalp) ointment

(s) Sulphur, camphor, carbolic acid, salicylic acid.


Other Scalp Preparations

Calcipotriol scalp lotion(Dovonex)

(s)

Xamiol® scalp gel (s) (calcipotriol & betamethasone)

Ceanel concentrate shampoo (cetrimide)

(s) Cost band for 150mL: B

Ketoconazole shampoo (Nizoral)

(s) Dermatologists and G.U.M. only. Cost band for 120mL: C

Selsun shampoo (Selenium sulphide)

(s) Cost band for 150mL:B

Stimulant lotion (s)

Enflornithine cream (Vaniqua)

(s) Endocrinologists

Anti - infective Skin Preparations Antibacterial Preparations Antibacterial Preparations Only Used Topically

Mupirocin ointment(Bactroban)

Treatment of MRSA infected wounds. Apply once daily to wound for 7 days before re-screening as per MRSA policy

Silver sulfadiazine cream(Flamazine)

Polymyxins (Polyfax Ointment)

Antibacterial Preparations Also Used Systemically

Chlortetracycline cream/ointment (Aureomycin)

(s)

Fusidic acid cream/gel(Fucidin)

(s)

Metronidazole 0.75% gel (s)

Metronidazole 0.8% gel For malodorous wounds.

Metronidazole 0.5% lotion (s)

Sodium fusidate ointment Apply 3 - 4 times daily, less often if dressings used.


Systemic Antibacterial Preparations Used in Dermatology

Doxycycline capsules/soluble tablets

(s) Dermatologists and G.U.M. only.

Erythromycin tablets Acne: 250 - 500mg 4 times a day.

Lymecycline 408mg Caps (Tertracycline 300mg)

Acne: 408mg OD x 8 weeks.

Minocycline tablets/sr tablets

(s)

Oxytetracycline tablets Acne: 250 - 500mg 4 times a day.

Trimethoprim Tablets Acne:300mg BD (unlicensed)

Antifungal Preparations

Clotrimazole cream/ powder/solution (for hairy areas)

Apply 3 times daily.

Itraconazole capsules (s) Dermatologists, GUM and Consultants only.

Ketoconazole cream (s)

Ketoconazole shampoo (s)

Miconazole cream (s)

Nystatin cream/ointment (s)

Terbinafine tablets/cream (s) Dermatologists and Consultants only.

Antiviral Preparations

Aciclovir cream/dispersible tablets

Parasiticidal Preparations

Scabies Refer to Dermatologists if possible. Itching may be relieved with calamine lotion or oral antihistamines.

Choice:

Permethrin dermal cream

Alternative:

Benzyl benzoate 25% application

(s) Irritant, may need up to 3 applications to be effective. Prescription by Dermatology only. Under 12 years use 1/2 strength, under 2 years use 1/3 strength, diluent water.


Headlice

Choice:

Malathion alcoholic lotion (Suleo M)

Malathion aqueous lotion (Derbac M)

Crab (pubic) Lice

Malathion aqueous lotion (Derbac M)

Preparations for Minor Cuts and Abrasions

Magnesium sulphate paste (for boils)

Skin Tissue Adhesive

Enbucrilate (Histoacryl)

Skin Cleansers and Antiseptics Alcohols and Saline

Sodium chloride for irrigation

Chlorhexidine Salts

Chlorhexidine alcoholic solution 0.5%, aqueous solution 0.5% pink/colourless

Chlorhexidine 0.015%, cetrimide 0.15% sachets 25mL, 100mL

Chlorhexidine gluconate 0.05% sachet, skin cleaner (Hibiscrub) spray 2.5%,0.1%,

Chlorine and Iodine

Weak alcoholic iodine solution (s)

Povidone iodine solution (alcoholic, antiseptic, dry powder spray, scalp and skin cleanser, surgical scrub)

Povidone iodine ointment


Phenolics

Triclosan (Manusept alcoholic hand rub, Aquasept Bath concentrate, aquasept)

Astringents, Oxidisers and Dyes

Aluminium acetate solution* (s) Requires preparation in Pharmacy.

Hydrogen peroxide solution (3%, 6%), cream 1.5%

Due to its potential hazards, this product should only be used in exceptional circumstances and must be prescribed by a doctor of registrar grade or above. Can be used to clean open, dirty, contaminated, traumatic wounds and infected, sloughy and necrotic wounds. May be used as a mechanical cleansing agent due to its foaming action. It is NOT recommended for clean wounds or closed or tunnelling wounds.

Potassium permanganate solution/tablets

(s)

Silver nitrate solution (0.25%, 0.5%, 5%)*/sticks

(s)

Antiperspirants Driclor (s)

Glycopyrrolate 0.05% soln.*

(s) Requires preparation in Pharmacy.


IMMUNOLOGICAL PRODUCTS AND VACCINES Contents (Click on heading to go to that section) Vaccines and antisera Immunoglobulins


Vaccines and antisera

BCG Vaccines

BCG freeze - dried vaccine

(s) Occupational Health only.

BCG diagnostic agents No licensed preparation for the Mantoux test is currently available. An unlicensed preparation, available in 2 and 10 units of Tuberculin PPD per 0.1mL is stocked. Please contact Medicines Information (ext 2096) for further information.

Haemophilus influenzae type B vaccine

Haemophilus B (Hib) vaccine

(s) Consultants only. Conjugated polysaccharide vaccine. 0.5ml by i.m. Injection or deep sub-cutaneous injection if there is a high risk of bleeding. See section 1 for immunisation of splenectomy patients.

Hepatitis vaccines

Hepatitis A vaccine (s) Occupational Health / Infectious Diseases/ School of Tropical Medicine / Gastroenterology / G.U.M. only.

Hepatitis B vaccine (s) Occupational Health / Infectious Diseases/ School of Tropical Medicine / Gastroenterology /G.U.M./ Haemodialysis patients only.

Twinrix (Hep A&B) vaccine

(s) For use by registrars and above in G.U.M.

Influenza vaccine

Influenza vaccine (s) Consultants only. See section 1 for immunisation of splenectomy patients.

Meningococcal vaccines

Meningococcal C conjugate

(s) Consultants only. 0.5ml by I.M. injection. May be given by deep sub-cutaneous injection if there is a high risk of bleeding. See section 1 for immunisation of splenectomy patients.

Meningococcal A & C vaccine



http://g.u.m/

Pneumococcal vaccine

Pneumococcal vaccine (s) Consultants only. Pneumovax II vaccine. 0.5ml by subcutaneous or intra-muscular injection. See section 1 for immunisation of splenectomy patients.

Varicella-zoster vaccine

Varicella-zoster vaccine (s) Relevant renal transplant patients only.

Tetanus Vaccines

On the advice of the Joint Committee on Vaccination and Immunisation (JCVI) the Department of Health has changed the current policy for tetanus immunisation in adult life.

To counter the declining immunity to diphtheria seen in adults Adsorbed Tetanus vaccine has been discontinued. Adsorbed Diphtheria (low dose) Tetanus and Inactivated Poliomyelitis

Vaccine is to be used in its place.

Adsorbed Diphtheria (low dose) Tetanus and Inactivated Poliomyelitis Vaccine for adults and adolescents

0.5mL by deep s.c or i.m. injection. See below appropriate use and course length.

Treatment of patients with tetanus - prone wounds The following are considered tetanus - prone wounds: a) Any wound or burn sustained more than 6 hours before surgical treatment of the

wound or burn. b) Any wound or burn at any interval after injury that shows one or more of the

following characteristics: i. significant degree of de - vitalised tissue ii. puncture type wound particularly animal bites iii. contact with soil or manure likely to harbour tetanus organisms iv. clinical evidence of sepsis


Specific Anti - Tetanus Prophylaxis Thorough surgical toilet of the wound is essential whatever the tetanus immunisation history of the patient.

Immunisation status Type of wound

Clean Tetanus prone

Last of 3 dose course, or reinforcing dose within last 10 years.

Nil Nil (but give dose of tetanus immunoglobulin 0.5mL by deep s.c/i.m. injection if infection risk is high e.g. contamination with manure).

Last of 3 dose course or reinforcing dose more than 10 years previously

Reinforcing dose Adsorbed diphtheria (low dose) Tetanus and inactivated poliomyelitis vaccine (0.5mL by deep s.c./i.m. Injection).

Reinforcing dose of Adsorbed Diphtheria (low dose) Tetanus and inactivated poliomyelitis vaccine 0.5mL PLUS human anti - tetanus immunoglobulin (250units)* by deep s.c./i.m. injection at different site to the vaccine e.g. other arm.

Not immunised or immunisation status unknown

A full 3 dose course of tetanus vaccine at one month intervals

A full 3 dose course of tetanus vaccine PLUS dose of human anti - tetanus immunoglobulin (250units)* by deep s.c./i.m. injection at different site to vaccine.

*Give 500units: a) if more than 24 hours since injury, b) if there is risk of heavy contamination or c) following burns. Note: Tetanus vaccine should not be given to anyone suffering an acute febrile illness

except in the presence of a tetanus - prone wound.

Immunoglobulins Human anti – tetanus immunoglobulin Prophylaxis: 250 - 500units by deep s.c. or

i.m.injection. See table on page 327 for appropriate use. Treatment: 150units/kg in multiple injection sites.

All other immunoglobulins are restricted by NHS directive to approved indications and patients only. Consultants will be asked to complete a form for the Trust Immunoglobulins Committee before stock can be issued. Contact Pharmacy for advice.


MEDICINES USED IN ANAESTHESIA Contents (Click on heading to go to that section) Anaesthesia and Driving Surgery and Long Term Medication General Anaesthesia

Intravenous Anaesthetics Inhalational Anaesthetics Antimuscarinic Medicines Sedative and Analgesic Peri-Operative Medicines Muscle Relaxants Drugs for reversal of neuromuscular blockade Antagonists for Central and Respiratory Depression Antagonists for Malignant Hyperthermia

Local Anaesthesia Protocol for administration of Lipid emulsion (Intralipid) to treat overdose of local anesthetic

Guidelines for the peri–operative beta–blockade of patients undergoing major surgery

Trust Clinical Policy for Continuation of Medicine Therapy in the Peri-Operative Period: a Guide for Ward Staff


Items marked with (s) in this section are restricted to Anaesthetists and Consultants in Intensive Therapy Medicine unless stated otherwise. Prescribers who have adequate and recognised training in their use may prescribe them. Anaesthesia and Driving Patients administered a general anaesthetic, sedatives (e.g. intravenous benzodiazepines) or analgesics during minor surgery (including day case surgery) should be warned about the risk of driving afterwards. The DVLA advise that it is the responsibility of the driver to ensure that he/she is in control of the vehicle at all times and to be able to demonstrate that is so, if stopped by the police. The DVLA also mention that it might also be reasonable for the driver to check his/her insurance policy before returning to drive after surgery. It should be noted that suitability to drive does not only include recovery from general anaesthetic – it includes issues such as unsuitability to drive due to pain etc. The dangers of taking alcohol should also be emphasised. Surgery and Long Term Medication The risk of stopping long - term medication before surgery is often greater than the risk of continuing it during surgery. For more information on which medicines can be stopped, refer to the Trust Clinical Policy regarding ‘continuation of medication in the peri-operative period’ which is included towards the end of this chapter. If you require further clarification contact an anaesthetist. For alternative routes of medicine administration, contact Medicines Information (ext 2096) or your ward pharmacist. Sealants and haemostatic agents used during surgery A variety of agents are available to augment traditional haemostatic techniques during surgery with varying components and licensed indications. Some of these products are classed as devices, others as drugs. Agents that are approved for use within the Trust and available from pharmacy are: Evicel Contraindicated in neurosurgery due to lack of data

Tisseel “Ready to use” Haemostasis, CSF leaks and small dural defects in

spinal surgery Not for use in active bleeding (Replaces Tisseel LYO)

Floseal For active bleeding sites in vascular spine tumour surgery


General Anaesthesia

Intravenous Anaesthetics

Etomidate injection (s)

Ketamine injection (CD) (s) Ketamine is also available as an oral solution (unlicensed). This is occasionally used as a pre-med / sedation e.g. in dental hospital it is used as a sedative with midazolam for patients with special needs.

Propofol 1% injection (s) Note – This preparation is based on a lipid emulsion. Monitor triglycerides closely, especially if the patient is receiving an additional source of intravenous lipids e.g. as part of a parenteral nutrition regime.

Thiopental [thiopentone] injection

(s) Available as a 500mg vial

Inhalational Anaesthetics

Desflurane (s)

Halothane (s) See CSM advise in BNF re: hepatoxicity

Isoflurane (s)

Sevoflurane (s)

Nitrous oxide 50% / oxygen 50% (Entonox)

Entonox is used to produce analgesia without loss of consciousness. It is also used for painful procedures including dressing changes (See separate Trust protocol ). Note - Exposure of patients to nitrous oxide for prolonged periods, either by continuous or intermittent administration may result in megaloblastic anaemia. Depression of white cell count may also occur.

Antimuscarinic Medicines

Atropine injection (s)

Hyoscine hydrobromide injection

Effective in reducing respiratory secretions. It also has sedative action, but may occasionally cause paradoxical excitement

Glycopyrronium bromide injection

(s)


Sedative and Analgesic Peri-Operative Medicines

Anxiolytics and Neuroleptics

Diazepam tablets / injection (Diazemuls).

Long – acting benzodiazepine. Drowsiness may occur for several hours after administration due to active metabolites. Repeated doses may lead to accumulation, especially in patients with hepatic and renal impairment.

Lorazepam tablets / injection Sedation more prolonged than for temazepam.

Midazolam injection (CD) The use of midazolam should be restricted to those prescribers who have adequate and recognised training in its use. If midazolam is to be used, flumazenil should be available (benzodiazepine antagonist) in case it is required to reverse the sedative effects of midazolam. Flumazemil has a shorter half-life than that of diazepam and midazolam, and there is a risk that patients may become re-sedated.

Temazepam tablets (CD) Short – acting benzodiazepine. Given orally, it has a shorter duration of action than oral diazepam. Anxiolytic and sedative effects last for about 90 minutes although there may be residual drowsiness after this. May need to consider lowering dose in hepatic impairment.

Non-Opioid Analgesics

Diclofenac tablets/suppositories/

injection

Max. total dose by any route is 150mg/24 hours. The maximum licensed duration of parenteral therapy is 48 hours and IV diclofenac should not be infused together with other medicines.

Ketorolac injection (s). By mouth – 10mg every 4 – 6 hours (elderly 6 – 8 hours); max 40mg daily; max duration 7 days By i.m. or i.v injection (over at least 15 seconds), Initially 10mg maximum. Then may increase to 10 – 30 mg every 4 – 6 hours as required; max 90mg daily (elderly and patients weighing <50kg max 60mg daily); max duration 2 days


Opioid Analgesics Note: Details of oral / transdermal opioid preparations are listed in Chapter 4

Alfentanil injection (CD) (s) It is available as a 500microgram/ml and a 5mg/ml injection. Note – Two strengths – one is TEN times more concentrated than the other. The higher strength is restricted for use in ITU only.

Fentanyl injection (CD) (s)

Morphine injection (CD) Available as 50mg/50ml syringe for patient controlled analgesia regimens

Pethidine injection (CD)

Tramadol capsules / injection

Tramadol has an opioid effect in addition to an enhancement of serotonergic and adrenergic pathways. Its use is restricted within the Trust.

Remifentanil injection (s)

Neuromuscular blocking drugs – ‘Muscle Relaxants’

Non-Depolarising Muscle Relaxants

Atracurium injection (s)

Cisatracurium injection (s)

Mivacurium injection (s)

Rocuronium injection (s)

Pancuronium injection (s)

Vecuronium injection (s)

Depolarising Muscle Relaxants

Suxamethonium injection (s)


Drugs for reversal of neuromuscular blockade These drugs are used to reverse the effect of the non-depolarising ‘muscle relaxants.’ Caution – May prolong action of depolarising drugs such as suxamethonium.

Neostigmine injection (s)

Neostigmine with Glycopyrronium injection (Robinul - Neostigmine)

Sugammadex

(s) Glycopyyronium prevents bradycardia, excessive salivation, and other muscarinic effects of neostigmine. (s) For reversal of neuromuscular blockade induced by rocuronium or vecuronium only. Restricted use.

Antagonists for Central and Respiratory Depression

Doxapram injection See Section 2 for administration details.

Flumazenil injection (s) Flumazenil may be used to reverse the central sedative effects of benzodiazepines. Flumazenil has a shorter half-life than that of diazepam and midazolam, and there is a risk that patients may become re-sedated. Repeated doses may be required.

Naloxone injection Naloxone may be used to reverse opioid-induced respiratory depression. It will also antagonise the analgesic effect. The dose may have to be repeated because of its short duration of action.

Antagonists for Malignant Hyperthermia

Dantrolene injection (s) Available in all trust operating theatres


Local Anaesthesia Topical Preparations

Ethyl chloride spray Lidocaine [lignocaine] 2% gel Lidocaine [lignocaine] 5% ointment Lidocaine [lignocaine] 10% spray Lidocaine [lignocaine] 4% spray (Laryngojet) Lidocaine [lignocaine] topical soln. 4%, 10% Lidocaine [lignocaine] with chlorhexidine antiseptic gel 2% Emla cream (Lidocaine [lignocaine] and Prilocaine) Adrenaline (epinephrine) 1 in 1000 topical solution Cocaine topical solution (CD) 2.5%, 4%, 10% Tetracaine (amethocaine) gel 4% (Ametop) (s)

Parenteral Preparations

Bupivacaine 0.25%, 0.5% with adrenaline (epinephrine) injection

Bupivacaine Heavy 0.5%

(s) (s) For intrathecal anaesthesia

Levobupivacaine 0.125% and Fentanyl 4micrograms/ml in 500ml Sodium Chloride 0.9% (CD)

(s) This solution is for epidural use only

Levobupivacaine injection injection 0.25%, 0.5%, 0.75%

(s) Note – Levobupivacaine 0.75% injection restricted for use in Ophthalmology Theatres.

Lidocaine [lignocaine] 0.5 - 2% with adrenaline (epinephrine) 1 in 80,000 to 1 in 200,000 injection.

Prilocaine 1%, 2%, 4% injection

Prilocaine 3% with octapressin injection

Ropivacaine injection 0.2% 200ml

(s) Epidural infusion

Dehydrated alcohol Injection. Used very occasionally for chronic pain blocks.


Protocol for administration of Lipid emulsion (Intralipid) for the management of severe local anaesthetic toxicity This policy is based on the Association of Anaesthetists of Great Britain & Ireland (AAGBI) safety guideline 2010.

Procedure

1. Gently shake bag of Intralipid 20% two or three times before use. 2. Immediately give an initial intravenous bolus injection of 20% lipid emulsion

1.5 ml/kg over 1 min AND start an intravenous infusion of 20% lipid emulsion at 15 ml/kg/hr

3. After 5 minutes give a maximum of two repeat boluses (same dose) if: • cardiovascular stability has not been restored or • an adequate circulation deteriorates

Leave 5 min between boluses A maximum of three boluses can be given (including the initial bolus)

4. Continue infusion at same rate, but: Double the rate to 30 ml/kg/hr at any time after 5 min, if:

• cardiovascular stability has not been restored or • an adequate circulation deteriorates

Continue infusion until stable and adequate circulation restored or maximum dose of lipid emulsion given Do not exceed a maximum cumulative dose of 12 ml/kg

Model example for resuscitating an adult weighing 70kg who has accidentally received a toxic dose of local anaesthetic and who has consequent cardiovascular collapse.

1. Take a 500 ml bag of Intralipid 20% from CD cupboard in Theatre (labelled ‘For use during resuscitation only’) and a 50 ml syringe. 2. Give an initial intravenous bolus injection of 20% lipid emulsion 100 ml over 1

min (Draw up 50 ml and give over 30 seconds, repeat for another 50ml) 3. Attach remaining Intralipid 20% bag (400ml) to a giving set and run it

intravenously at 1000ml/hr 4. After 5 minutes give a maximum of 2 repeat boluses of 100ml (if indicated) 5. Continue infusion at same rate but double rate to 2000 ml/hr at any time (if

indicated) Do not exceed a maximum cumulative dose of 840 ml

Exclusions: Allergy to intralipid.

Pre-existing severe disorders of fat metabolism


Guidelines for the peri–operative beta–blockade of patients undergoing major surgery Beta-blockade should be started pre-operatively and continued post-operatively according to the following guidance. The ultimate decision on whether or not to implement this guideline rests with the responsible anaesthetist. Additionally, modification may be necessary when it is planned to carry out regional anaesthesia. For further information contact: Drs C.J.R. Parker, R. Wenstone and O. Zuzan

Indications Patients who are scheduled to undergo a major surgical procedure e.g.intraperitoneal, intrathoracic, peripheral vascular surgery or replacement of a large joint and who have any of the following risk factors

Risk factors Age > 70 years Current angina Previous myocardial infarction Congestive cardiac failure Previous cerebrovascular accident Diabetes, requiring treatment other than dietary restriction alone Renal dysfunction (defined as creatinine > 177 micromol/L)

Contra-indications (i.e. exclude the following):

Patients who have asthma. Patients who fulfill the criteria for NYHA class IV cardiac failure (i.e.

symptoms with any activity or dyspnoea at rest) Patients who have 2º or 3º heart-block

Protocol: 1. If already receiving regular beta-blocker medication this must be continued. 2. If not already receiving regular beta-blocker medication, start atenolol as follows:

Start 50 – 100 mg daily orally from admission. Titrate to a heart rate of < 65/min.

50 mg orally with premed (or 5 – 10 mg IV in the anaesthetic room pre-op at the discretion of the anaesthetist) and

50 – 100 mg/day orally (or 5 mg IV BD if GI route not available) for 7 days or until discharge if sooner.

Hold doses if HR < 55/min or systolic BP < 100mmHg. Reduced dosage may be needed in patients with renal impairment.


Guidelines regarding continuation of medicines in the Peri-Operative Period This section aims to provide a brief overview of the administration of medication in the peri-operative period, and should be a useful guide to clinical staff who routinely prescribe and administer medicines during the peri-operative period. The guide includes brief information relating to those medicines which MUST be continued peri-operatively, and those which may require withholding peri-operatively.

It is beyond the scope of this section to include examples of all drug form, route and formulation changes. Please contact Medicines Information (ext 2096) for further information

BNF Chapter Medicine type / name

Recommendation / Comment

1: Gastro - Intestinal System

Antacids Usually continued, to reduce risk of acid aspiration

Antispasmodics / Antimuscarinics

Usually continued, but may omit on day of surgery to reduce risk of ileus

H2 antagonists / Proton-pump inhibitors

Usually continued, to reduce risk of rebound acid secretion

Some patients may benefit from short-term initiation of H2 antagonist / PPI therapy in the NBM period

Anti-diarrhoeals Usually continued but review need in the light of presenting complaint

Aminosalicylates Usually continued

Laxatives Usually continued, but note contra-indications for each and review in the context of presenting complaint

Isphagula is contra-indicated in intestinal obstruction and colonic atony

Docusate is contra-indicated in abdominal pain, nausea, vomiting or intestinal obstruction

Senna is contra-indicated in undiagnosed acute or persistent abdominal symptoms

2: Cardiovascular system

General comment: continuing antihypertensive medicines improves cardiovascular stability and reduces morbidity. Always check BP before prescribing / administering an anti-hypertensive, and if unsure check with anaesthetist.

Oral inotropes e.g. digoxin

Usually continued Refer to anaesthetist if hypokalaemic,

hypomagnesaemic or hypercalcaemic, as these can increase myocardial sensitivity to digoxin, which may result in toxic digoxin levels.


BNF Chapter Medicine type / Recommendation / Comment name

Check level as part of routine pre-op assessment (at least 6-8 hrs after previous day’s dose). This may not be necessary in patients who are stable on a maintenance dose.

100 micrograms IV digoxin approximately equivalent to 125 micrograms oral digoxin

Thiazide / Loop diuretics e.g. bendroflumethiazide and furosemide

Usually continued, especially if used for heart failure or advanced renal failure. May omit if patient admitted for minor procedure under local anaesthetic.

Antihypertensive and diuretic effect (especially loop diuretics) may be reduced by concomitant NSAIDs such as indometacin, piroxicam, diclofenac and naproxen.

Max i.v. rate for furosemide = 4mg/minute

Potassium-sparing diuretics e.g. amiloride, co-amilofruse, co-amilozide, spironolactone etc

Usually continued, but anaesthetist or surgeon may omit on the morning of surgery because hyperkalaemia may arise as a result of reduced renal perfusion post-surgery. An alternative diuretic may be prescribed.

Anti-arrhythmics e.g. amiodarone

Usually continued, to reduce risk of peri-operative arrhythmias

All parenteral administration MUST be accompanied by ECG monitoring

Beta-blockers Usually continued to avoid withdrawal symptoms and decrease peri-operative morbidity.

In some cases e.g. post-thyroidectomy, dose may gradually be tapered to zero

If stopped may worsen cardiovascular morbidity.

Centrally acting anti-hypertensives

Usually continued, to avoid rebound symptoms and hypertensive crisis

Continuation decreases peri-operative morbidity. If stopped may worsen cardiovascular morbidity.

Alpha-adrenoceptor blockers

Usually continued. Continuation reduces peri-operative cardiovascular morbidity e.g. myocardial ischaemia and improves haemodynamic stability

ACE inhibitors Usually continued, unless otherwise specified by the anaesthetist.

If discontinuation requested by anaesthetist, the half-life of the drug needs to be taken into consideration to decide when to stop the ACEI - stop captopril and quinapril 12 hours pre-surgery, and enalapril, lisinopril and ramipril at least 24 hours pre-surgery. Monitor BP closely



Angiotensin II antagonists

Usually continued, unless otherwise specified by the anaesthetist.

Nitrates Usually continued to avoid recurrence of symptoms.

Do NOT crush modified release preparations. Will need to convert to a lower dose shorter acting preparation with more frequent dosing. Other options for administering nitrates include trandermal delivery (e.g GTN patch) and parenteral route (isosorbide dinitrate infusion) – the latter requires specialist monitoring.

Potassium channel activators


Calcium channel blockers

Usually continued. Risk of rebound hypertension or coronary artery spasm if stopped abruptly

Avoid using sublingual nifedipine capsules for treating hypertension, as these have been associated with an increased risk of strokes

Warfarin Usually converted to heparin or a low molecular weight heparin.

For specific advice refer to Trust policy “Management of the warfarinised patient requiring urgent surgery” or contact Haematology

Aspirin / Clopidogrel Where aspirin is to be withdrawn, this should normally be done at least 7-10 days before surgery in patients at high risk of postoperative bleeding. When deciding whether or not continue aspirin, a balance between risk of a VTE event and bleeding needs to be taken into account. Usually continued in vascular surgery.

Dipyridamole Stop 24 hours before surgery, unless otherwise directed by anaesthetist (manufacturer’s advice). Usually continued in vascular surgery.

3: Respiratory system

Theophylline Usually continued, unless otherwise specified by the anaesthetist.

Due to its narrow therapeutic index, theophylline levels need to be guided by therapeutic drug level monitoring. Consult the Medicines Information (ext: 2096) for information relating to formulation/dose/preparation substitution.

Corticosteroids MUST continue corticosteroid replacement May need to convert oral prednisolone to i.v.

hydrocortisone 5mg oral prednisolone approximately equivalent to



20mg i.v. hydrocortisone Requirements increased due to stress of surgery so

may need extra i.v. hydrocortisone above equivalence of usual oral dose.

Inhalers e.g. salbutamol and ipratropium bromide

Usually continued. Inhaled therapy can be substituted with nebulised therapy where appropriate.

4: Central nervous system

Hypnotics Usually continued, unless otherwise specified by the anaesthetist.

Risk of withdrawal symptoms if omitted

Anxiolytics Usually continued, unless otherwise specified by the anaesthetist.


Barbiturates Usually continued, unless otherwise specified by the anaesthetist.


Lithium Usually continued but MAY stop at least 24 hours pre-operatively due to potential electrolyte and fluid balance disturbance. Any decision to stop lithium must be first discussed with the patients psychiatrist.

Watch for renal impairment or hyponatraemia, as

these can contribute to lithium toxicity. Avoid NSAIDs if possible, these reduce the

elimination of lithium. Avoid dehydration (caution with diuretics) Lithium carbonate 200mg approximately equivalent

to Lithium citrate 509mg (liquid)

TCADs / SSRIs Usually continued, unless otherwise specified by the anaesthetist.

Note – SSRIs can interact with medicines such as pethidine and tramadol (which block presynaptic reuptake of serotonin), to precipitate ‘serotonin syndrome,’ which can be fatal.

Due to long half-life, omission of a single dose unlikely to cause withdrawal symptoms, although it has been reported with prolonged dose omission

In the case of tricyclic anti-depressants (TCADs), there is a risk of intra-operative arrythmias if continued, hence continued administration must be highlighted

MAOIs MUST always check with anaesthetist before giving dose.

MAOIs and pethidine may result in excitatory reactions due to excessive serotonergic activity.



CNS depression has also been reported. If continued, will require ‘safe anaesthetic’

technique, due to potential for interaction with anaesthetic agents

Analgesia Usually continued unless otherwise specified by the anaesthetist. Post-operative analgesic requirements are additional to chronic therapy

Anti-epileptics MUST continue. Very important to maintain therapeutic

concentrations to avoid seizures. Carbamazepine 100mg tablets approximately

equivalent to Carbamazepine 125mg suppositories

Sodium valproate i.v. dose approximately equivalent to oral dose

Phenytoin sodium 100mg capsule approximately equivalent to 90mg phenytoin liquid. Note – For tube-fed patients, the feed should be stopped for 2 hours before phenytoin dose and 2 hours after dose.

Phenobarbitone – Injection only licensed for status epilepticus

Anti-parkinsonian medicines


Continue co-careldopa or co-beneldopa if able to. MUST inform anaesthetist, if on selegiline.

Selegiline interacts with pethidine to cause hyperpyrexia and CNS toxicity. If to continue selegiline, use ‘safe anaesthetic technique.’ If stopped may need to increase l-dopa dose

Avoid prochlorperazine and metoclopramide in patients with Parkinson’s disease

6: Endocrine system

General guidance for type 1 and type 2 diabetic patients using insulin) Omission of food and fluids in type 2 diabetic patients who are either diet-controlled or who take oral hypoglycaemics ONLY

Pre-operative assessment Note the presence / absence of complications e.g.

retinopathy, nephropathy, hypertension, ischaemic heart disease, neuropathy (peripheral and autonomic) and foot problems (vascular or neuropathic). Take special care of the heels and malleoli (either side of the ankle joint) in patients with neuropathic feet.

Investigations Urinary protein, ECG, U and E profile, HbA1c.

Patients with uncontrolled diabetes mellitus should be referred to a diabetes specialist.

Admission to hospital and timing of operation Admit at least 24 hours prior to surgery, where

possible. The operation should preferably be in the morning.



Oral Anti-diabetics

Infusion fluids Consider avoiding lactate containing infusions e.g.

Hartmann’s. Other Take the opportunity to assess the patient’s skills in

injection technique, use of blood glucose monitoring sticks, use of urine testing sticks etc. Re-educate if problems are identified

Morning list - Restrict to clear non-fizzy fluids from midnight of the previous night. Render patient ‘nil by mouth’ from 06.00 on day of surgery, therefore NO breakfast on the morning of surgery.

Afternoon list – Can have light breakfast on day of surgery before 0700. Then restrict to clear non-fizzy fluids until 11.00. After 11.00 render patient ‘nil by mouth.’

If taking sulphonylureas or metformin, see below; Sulphonylureas Morning list - Omit oral short-acting

sulphonylureas e.g. gliclazide on the morning of surgery.

Afternoon list – Take morning short-acting sulphonylureas, but omit lunchtime dose.

Longer acting sulphonylureas may need to be stopped during the NBM period

Patients taking sulphonylureas may sometimes require converting to insulin. This decision should only be taken by a senior doctor or anaesthetist

Restart sulphonylurea at usual pre-operative dose after first post-operative meal

Metformin Doses usually omitted on day of surgery. Metformin may be stopped 24-48 hours before

surgery (or patients due to receive radio-contrast media), to avoid risk of precipitating lactic acidosis, especially in patients with renal impairment. Recheck U and E’s before recommencing metformin.

For patients using insulin

MORNING OPERATION LIST On the night before surgery; Administer all short and intermediate/long-acting

insulins on the night prior to surgery, unless otherwise specified by the anaesthetist

Restrict to clear non-fizzy fluids from midnight of the night prior to surgery until 0600 on day of surgery.



On the morning of surgery; Render patient ‘nil by mouth’ from 06.00 on day of

surgery. (NO breakfast on morning of surgery) Omit all morning ‘s.c.’ insulin doses and convert to

‘i.v.’ insulin regimes e.g. ‘GLIK / Alberti’ or ‘sliding scale’ – Refer to separate Trust guidelines (page 219)

Reconverting to subcutaneous insulin; Continue i.v. insulin regime until first post-operative

meal Give first s.c. insulin injection 20 minutes BEFORE

the i.v. insulin regime is discontinued and the patient starts the meal For minor operations where the patient is expected to recover and start eating soon, the patient’s usual insulin regimen may be restarted.

AFTERNOON OPERATION LIST On the night before surgery; Administer all short and long-acting insulins on the

night prior to surgery, unless otherwise specified by the anaesthetist

On the morning of surgery; Can have light breakfast on day of surgery. Then

restrict to clear non-fizzy fluids until 11.00. After 11.00 render patient ‘nil by mouth.’

Omit all morning ‘s.c.’ insulin doses and convert to ‘i.v.’ insulin regimes e.g. ‘GLIK / Alberti’ or ‘sliding scale’ – Refer to separate Trust guidelines (See here)

Reconverting to subcutaneous insulin; Continue i.v. insulin regime until first post-operative

meal Give first s.c. insulin injection 20 minutes BEFORE

the i.v. insulin regime is discontinued and the patient starts the meal For minor operations where the patient is expected to recover and start eating soon, the patient’s usual insulin regimen may be restarted.

Levothyroxine Usually continued, unless otherwise specified by the anaesthetist.

If NBM period prolonged, convert oral levothyroxine (thyroxine) to liothyronine injection

Oral levothyroxine (formally known as thyroxine) 100micrograms approximately equivalent to liothyronine injection 20 micrograms

Anti-thyroid medicines e.g. carbimazole

Usually continued, unless otherwise specified by the anaesthetist, for example following total thyroidectomy.

Anti-thyroid drugs may be continued as part of a



‘block-replace’ regime following partial thyroidectomy

HRT Usually continued, unless otherwise specified by the anaesthetist.

Assess risk of venous thromboembolism versus recurrence of menopausal symptoms.

If to stop, need to discontinue 4 weeks before major elective surgery.

Combined Oral Contraceptives


Assess risk of venous thromboembolism versus pregnancy.

If to stop, discontinue 4 weeks (some manufacturers state 6 weeks) pre-surgery, and re-started at the first menses occurring at least 2 weeks after full mobilisation.

Progesterone Only Pills


No evidence to suggest increased risk of PE/DVT, but there have been reports of desogestrel and gestodene being associated with increased risk of venous thromboembolism.

8: Treatment of malignant disease and immuno - suppression

Immuno - suppressants


Do NOT open/crush mycophenolate capsules/tablets, to avoid risk of exposure to medicine

Tamoxifen Consider stopping 4 weeks (some manufacturers suggest 6 weeks) before surgery due to increased risk of thromboembolism. Discuss with the breast unit before discontinuation.

If stopped, recommencing should be guided by degree of mobility and risk of continued omission of tamoxifen

If continued, consider for thromboprophylaxis as appropriate (See separate guidelines)

10: Musculo – skeletal and joint diseases

NSAIDs Usually continued, unless otherwise specified by the anaesthetist.

Assess risk of bleed versus pain management.

11: Medicines acting on the eye

Eye drops for glaucoma

Usually continued, to avoid risk of increase in intraocular pressure if stopped

Herbal medicines

Echinacea Discontinue as far in advance of surgery as possible because of immuno-stimulatory effect

Note – Long term use has potential for immunosuppression



BNF Chapter Medicine type / name

Recommendation / Comment

Key reference for this section – ‘Herbal Medicines and Perioperative Care.’ JAMA.2001; 286: 208-216.

Ephedra Stop at least 24 hours before surgery Causes increase in heart rate and blood pressure With MAOIs may result in life-threatening

complications

Garlic Stop 7 days before surgery due to its potential for irreversible inhibition of platelet function, hence increased risk of bleeding

Gingko biloba Stop 36 hours before surgery due to its potential for inhibiting platelet-activating factor, hence increased risk of bleeding

Ginseng Stop 7 days before surgery due to its potential for irreversible inhibition of platelet function, hence increased risk of bleeding

Kava Stop at least 24 hours before surgery because it has the potential to increase sedative effects of anaesthetics

St John’s Wort Stop 5 days before surgery because it induces cytochrome p450 enzymes, hence resulting in increased metabolism of medicines metabolized via this pathway.

Valerian Continue until the day of surgery because abrupt withdrawal may be associated with a benzodiazepine-like withdrawal symptom