1 | P a g e V e r s i o n 1 Adapted for use by Acacia Sooklal Senior Clinical Pharmacist/Enhancing Quality AKI Group

ACUTE KIDNEY INJURY

(AKI)

MEDICATION

OPTIMISATION

TOOLKIT

Written by: Renal Pharmacy Group March 2012

Adapted For use by: Acacia Sooklal

Senior Clinical Pharmacist/ Enhancing Quality AKI Group

Medway NHS Foundation Trust

Approved: August 2015

Review Date: August 2017

2 | P a g e V e r s i o n 1 Adapted for use by Acacia Sooklal Senior Clinical Pharmacist/Enhancing Quality AKI Group

Renal Pharmacy Group AKI working group

Sue Shaw (Working Group

Chair)

Royal Derby Hospital NHS Foundation Trust

Caroline Ashley (RPG Chair) Royal Free Hampstead NHS Trust

Israr Baig Gloucestershire Royal Hospital

Rania Betmouni Hammersmith Hospital, Imperial College

Healthcare NHS Trust

Adrian Coleman Kent and Canterbury Hospital, East Kent

Hospitals University NHS Foundation Trust

Emma Cooper Southampton University Hospitals NHS Trust

Alison Hodgetts Litchfield Hospital

Emily Horwill University Hospitals Coventry and Warwickshire

NHS Trust

Clare Morlidge East and North Hertfordshire NHS Trust

Reena Popat

Lynn Ridley York Hospital

Contributors: AKI National Delivery Group

Adapted for use at Medway NHS Foundation Trust by:

Medway AKI Enhancing Quality Team

Dr Syed Consultant Physician in Acute Medicine

Acacia Sooklal Senior Clinical Trials Pharmacist

Learieann Alexander Enhancing Quality Sister

Sarah Leng Head of Clinical Effectiveness and Quality

Improvement

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This ‘Acute Kidney Injury -

Medication Optimisation Toolkit’ is designed to ensure that the

medications received by patients with AKI are optimised.

When a patient is admitted with AKI, a thorough review of their medication is required:

To eliminate potential cause / risk / contributory factor(s) for AKI

To avoid inappropriate combinations of medications

To reduce adverse events

To ensure that doses are correct

To ensure all medicines prescribed are clinically appropriate.

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Acute Kidney Injury – Medication Optimisation Proforma

1) Initially consider which medications the patient is taking and how it will impair renal function.

Consider Acute Nephrotoxic Drug Action

Contrast media

ACE Inhibitors CONSIDER

NSAIDs

Diuretics WITHOLDING

Angiotensin receptor blockers

2) Review Medication

DRUGS TO STOP ON ADMISSION

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor blockers

ACEI / ARB

ACE inhibitors and ARBs reduce renal blood flow, which in combination with AKI can lead to increased damage to the kidney. It is recognised that withholding ACE Inhibitors when a patient is diagnosed with AKI allows the patient’s renal function to improve. (4)

Metformin

Consider stopping and monitoring the patient’s blood sugar control. If appropriate consider an alternative or insulin for blood sugar control. There is a risk of lactic acidosis when Metformin is used in patients with renal impairment. Lactic acidosis is a rare, but serious condition which is caused by the accumulation of Metformin. Reported cases of lactic acidosis in patients on Metformin have occurred primarily in diabetic patients with significant renal failure. (2)

NSAIDs / COX II inhibitors

Consider withholding in patients with AKI. The adverse effects of NSAIDs are mediated via

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inhibition of prostaglandin synthesis by non-specific blocking of the enzyme cyclooxygenase leading to vasoconstriction and reversible mild renal impairment in volume contracted states. (1)

Diuretics The use of diuretics is dependent on the patient’s volume state. Higher doses may be needed to achieve diuresis in patients who are fluid overloaded, however over-diuresis causing fluid depletion can cause or exacerbate AKI. (consider risk vs benefit)

DRUGS TO AVOID/REDUCE DOSE/MONITOR LEVELS/or WITHOLD

ACE Inhibitors/ Angiotensin Receptor Blockers

(ACEI / ARB)

Instead of stopping ACE inhibitors, if the patient’s renal impairment is not severe, it may be more appropriate to reduce the dose of the ACE inhibitor or Angiotensin II receptor blockers. Factors that would need consideration include: baseline creatinine, eGFR, other medication prescribed (e.g. antihypertensives) and past medical history (consider risk vs benefit)

Analgesics e.g. Opioid analgesics*

Opioids (especially Morphine and Pethidine) can accumulate, which can lead to respiratory depression (5) therefore should be avoided in renal impairment.

Contrast media* Withhold during admission- There may be instances where use may outweigh risk, to be reviewed on individual patient basis in those situations.

DMARDs e.g. Methotrexate

May require dose reduction (see additional information below in table below).

Metformin Risk of lactic acidosis-extensively excreted by the kidneys. (See above)

Antibiotics / antifungals / antivirals*▪

Please refer to the Medway NHS Foundation Trust antibiotic guidelines. Contact the ward pharmacist, the antimicrobial pharmacist (Ext 6033) or microbiology for advice. http://www.medway.nhs.uk/resources/antibiotic-guidelines/

Anticoagulants including low molecular weight heparins, warfarin*

May require dose reduction, consult the ward pharmacist, anticoagulant pharmacist or haematology consultant for advice.

Digoxin This is a narrow therapeutic drug and may accumulate in patients with renal impairment. Digoxin levels should be monitored in patients at increased risk of accumulation. Blood should be taken 6 hours or more after the last dose of digoxin. The digoxin level should be maintained

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between 0.8- 2.0 ng/ml. Serum potassium can affect digoxin toxicity; therefore it is important to monitor the patient’s potassium levels. Hypokalaemia can increase the risk of toxicity. (3)

Diuretics See information above

Antihypertensives Consider withholding in patients diagnosed with AKI. Usual recommendation is to withhold and re-introduce when AKI has resolved. Careful consideration is needed when antihypertensives are reintroduced post an episode of AKI episode. Monitor the patient’s BP and renal function and ensure they are adequate before initiating treatment.

Antiepileptics (Including Phenytoin, Gabapentin, Pregabalin)

Please contact the ward pharmacist for advice about dosing in patients with AKI and CKD.

Chemotherapy Please contact the Haematology/Oncology Consultant or Pharmacist for specialist advice about dose modifications. If the patient is enrolled onto a clinical trial please contact the Clinical Trials Pharmacist-Ext 3423

Hypoglycaemic agents May require dose reductions- seek advice from the ward pharmacist.

Immunosuppressants e.g. ciclosporin – seek advice from transplant centre

Discuss with the Consultant and seek advice from the ward pharmacist or the transplant centre.

Lipid-lowering agents e.g. fibrates, statins

Seek advice from the ward pharmacist

Allopurinol May require dose adjustments

3) Educate the patient before discharge; ensure that the patient is informed about medication stopped during admission, whether any medication needs to be restarted and whether monitoring is required.

4) Ensure information is documented on the EDN. Write clear instructions to the GP as to the plan for restarting any medication that may have been withheld or stopped during admission due to AKI.

Please add sufficient detail to the patient’s EDN. Information should be included about monitoring, dose adjustments and recommendations. If

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possible add instructions on how to manage the medication in light of blood results. This is important to ensure that the patient is managed appropriately when they are transferred between secondary and primary care.. An AKI section has been incorporated into the EDN which must be completed on discharge.

Additional Information

Speciality/Area Current Information Contacts

Acute Pain Discuss with the ward Pharmacist or discuss options with the Acute Pain Team. Considerations that should be taken into account:

- NSAIDs should be stopped in patients with renal impairment

- Monitoring the patient’s renal function as there may be accumulation when opioids are used which may lead to respiratory depression.

- Reduce the dose of Paracetamol in renal impairment.

Acute Pain team via switchboard.

Palliative Care Refer to the ward Pharmacist or discuss options with the palliative care team.

Palliative Care consultant. Ext 3807 (9am-5pm) Contacted via switch board.

Rheumatology Medication (DMARDS, Methotrexate, Corticosteroids)

Treatment is assessed on an individual patient basis. Please contact the ward Pharmacist for advice on dose adjustments in renal impairment Additional information can be found on the British Rheumatology Website see below) http://www.rheumatology.org.uk/BHPR/

(Registrar) Ext: 3904/3903

Antibiotics/ Antimicrobials

Refer to Medway NHS Foundation Trust’s antimicrobial guidelines via the intranet on “Quick Links”. These include:

Gentamicin

Vancomycin

Teicoplanin

Antimicrobial Pharmacist Ext: 6033

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Please contact the ward Pharmacist for advice on dose adjustments in patients with renal impairment.

Anticoagulants LMWH

Please contact the ward Pharmacist for advice on dose adjustments in patients with renal impairment.

Anticoagulant Clinic Medway NHS Foundation Trust. Ext: 3902

Mental Health Discuss with the ward pharmacist or discuss with the mental health pharmacist. Refer to The Maudsley Prescribing Guidelines for further advice.

Mental Health Pharmacist. Ext 6650

Anti-retrovirals / HAART

May require dose adjustments, please contact the ward pharmacist, consult product literature and/or discuss with the HIV Pharmacist.

It may also be beneficial to discuss with the HIV Consultant. Please see website below for additional information:

http://hivinsite.ucsf.edu/InSite?page=md-rr-18

HIV Pharmacist.

Ext : 3876

The Renal Drug Handbook and manufacturers’ summary of product characteristics (www.medicines.org.uk) are also available for additional information.

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Specific Medication List

The following list is not exhaustive, remember to consider ALL medications including any “usual” long term medications.

Remember to check medication history thoroughly and ask about “Over the Counter” preparations, herbal remedies / teas and alternative therapies. Check recreational use of drugs (cocaine, ketamine etc.) as these have been implicated in rhabdomyolysis.

Please contact the ward pharmacist for any advice regarding dose adjustments and management of patients with AKI

Drug Problem Action in presence of AKI Patient education

Analgesics

NSAIDs / COX II

inhibitors Acute interstitial nephritis

Altered haemodynamics

Avoid Avoid taking whilst at risk of dehydration.

Opioid analgesics Accumulation of active

metabolites – increased CNS

side effects.

Avoid XL / SR preparations.

Reduce dose of short acting preparation

May accumulate in acute kidney injury. Seek

advice if at risk of dehydration. If needed, use

opiates with minimal renal excretion e.g.

fentanyl.

Tramadol Accumulation Reduce dose

Avoid XL preparations

May accumulate in acute kidney injury.

Seek advice if at risk of dehydration.

Antibiotics / Antifungals / Antivirals (See antibiotic guidelines on the intranet)

Aciclovir Crystal nephropathy.

Accumulates in kidney injury

Avoid rapid infusions. Infuse

IV over one hour

Reduce dose Encourage patient to drink plenty.

Seek medical advice if at risk of dehydration.

Aminoglycosides Tubular cell toxicity Avoid if possible / reduce dose / increase

dose interval. Monitor

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drug levels and renal function 2 – 3 times per

week.

Drug Problem Action in presence of AKI Patient education

Antibiotics / Antifungals / Antivirals (See antibiotic guidelines)

Amphotericin IV –

Fungizone®

Tubular cell toxicity Hypokalaemia

Avoid rapid infusion

Avoid. Consider Ambisome® preparation

Co-trimoxazole Crystal nephropathy

Hyperkalaemia

Reduce dose.

Seek medical advice if patient is fluid

restricted and requiring IV infusion

preparation.

Encourage patient to drink plenty.

Seek medical advice if at risk of dehydration.

Fluconazole Accumulation Reduce dose.

Check for drug interactions that may be

contributing to AKI.

Interactions, e.g. withholding statins as risk of rhabdomyolysis.

Ganciclovir IV Crystal nephropathy

Accumulates in kidney injury

Avoid rapid infusions. Ensure

IV is infused over one hour.

Reduce dose

Penicillins Acute interstitial nephritis

Glomerulonephritis

Accumulation leading to

possible increase in CNS

side effects

Reduce dose

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Teicoplanin Accumulation Reduce dose

Monitor levels

Antibiotics / Antifungals / Antivirals (See antibiotic guidelines)

Drug Problem Action in presence of AKI Patient Education

Tetracycline Acute interstitial nephritis

Accumulation

Avoid

Trimethoprim Acute interstitial nephritis

Hyperkalaemia

Accumulation

Avoid

Valganciclovir Accumulates in kidney injury Reduce dose- Refer to Renal Drug

Handbook

Vancomycin Acute interstitial nephritis

Accumulation

Reduce dose / increase dose interval- Refer

to Vancomycin guidelines or contact your

ward pharmacist.

Monitor levels

Drug Problem Action in presence of AKI Patient education

Antiepileptics (including drugs used for neuropathic pain)

Gabapentin Accumulation in kidney

impairment – increase in CNS

side effects

Reduce dose

Phenytoin Acute interstitial nephritis Monitor levels

Pregabalin Accumulation leading to

increase in side effects Reduce dose

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Drug Problem Action in presence of AKI Patient education

Antihypertensives Hypotension

May exacerbate hypoperfusion

Longer acting, renally cleared may

accumulate in renal impairment

Consider withholding / reduce dose

depending on clinical signs

ACEI / ARBs / Aliskiren Altered haemodynamics

Hyperkalaemia

Avoid. Seek nephrologist advice if

undergoing contrast procedure or at risk

of AKI.

Avoid taking whilst at risk of

dehydration. Seek medical advice if at

risk.

Contrast media

Diuretics Hypoperfusion

Loop diuretics preferred as thiazides

ineffective

Monitor and adjust dose as necessary

Seek nephrologist advice if undergoing

contrast procedure or at risk of AKI.

Dose reduction may be required.

Seek medical advice if at risk of

dehydration

Diuretics – potassium

sparing Hyperkalaemia

Hypoperfusion

Avoid Dose reduction may be required. Seek

medical advice if at risk of dehydration

Hypoglycaemic

agents Accumulation leading to

hypoglycaemia Avoid MR / longer acting agents

Reduce dose

Monitor BMs

Metformin Lactic acidosis

Accumulation

Avoid. Seek nephrologist advice if

undergoing contrast procedure or at risk

of AKI.

Avoid taking whilst at risk of

dehydration. Seek medical advice if at

risk.

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Drug Problem Action in presence of

AKI Patient education

Immunosuppressants (DMARDs, chemotherapy)

Calcineurin inhibitors e.g. ciclosporin,

tacrolimus

Accumulation and risk of nephrotoxicity Seek advice of

transplant centre

regarding monitoring

levels and dose

adjustment.

May accumulate in kidney

injury. Seek medical advice /

advice from transplant team if

at risk of dehydration.

Methotrexate Crystal nephropathy

Accumulation increases side effects

Avoid

Monitor levels and

consider folinic acid

rescue

Correct fluid balance

May accumulate in kidney

injury. Seek medical advice if

at risk of dehydration.

Others

Allopurinol Acute interstitial nephritis

Allopurinol and its metabolites accumulate in

kidney impairment

Reduce dose

5 –aminosalicylates Nephrotoxic – tubular and glomerular damage. Avoid

Anticholinergic side effect of drugs:

Antihistamines, Anti-

psychotics, Antispasmodics

Urinary retention –

Consider as possible cause of drug induced

kidney injury

Reduce dose

Avoid XL preparations

If difficulty in passing urine

develops, seek medical

advice

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Drug Problem Action in presence of

AKI Patient education

Others (continued)

Ayurvedic medicines Nephrotoxicity has been reported.

Some ayurvedic medicines also contain heavy

metals

Avoid

Check drug history

thoroughly.

Patients may not

consider herbal

preparations / teas as

medicines

Seek medical advice if

considering alternative

medicines for effects on

disease, side effects and

possible interactions.

Bisphosphonates IV Nephrotoxic –

in high doses and short duration infusions

Reduce dose and infuse

at correct rate

Colchicine Diarrhoea / vomiting

Dehydration

Exacerbating hypoperfusion if also taking a

NSAID

Reduce dose Short course of 2 -3 days

should be followed. Seek

medical advice if diarrhoea

and vomiting develops.

Digoxin Accumulation

Aggravates hyperkalaemia

Reduce dose

Monitor drug level

May accumulate in acute

kidney injury. Seek medical

advice if at risk from

dehydration

Herbal preparations Chinese herbal medicines with aristocholic acid

implicated in interstitial nephritis. Cat’s Claw has

anti-inflammatory properties and has been

implicated in causing AKI and hypotension with

Avoid

Check drug history

Seek medical advice if

considering alternative

medicines for effects on

disease, side effects and

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antihypertensives.

Nephrotoxic effects of herbal medicines may be

exacerbated when used with concomitant

nephrotoxic medicines

thoroughly.

Patients may not

consider herbal

preparations / teas as

medicines

possible interactions.

Drug Problem Action in presence of

AKI Patient education

Others continued

Lipid-lowering agents e.g. fibrates,

statins

Rhabdomyolysis Avoid Stop if develop unexplained /

persistent muscle pain. Seek

medical advice

Lithium Accumulation

Chronic interstitial nephropathy

Kidney impairment exacerbated in volume

depletion and in combination with ACE inhibitors

/ ARB / NSAIDs

Avoid where possible

Monitor levels

Seek advice for

alternative

Encourage patient to drink

plenty. Seek medical advice if

at risk of dehydration

Nitrates / Nicorandil Hypotension

May exacerbate hypoperfusion

Consider withholding /

reduce dose depending

on clinical signs

Avoid taking whilst at risk of

dehydration. Seek medical

advice if at risk.

Anticoagulants

Low molecular weight heparins (See In house guidelines)

Warfarin INR may be raised due to acute rise in urea and warfarin displacement from binding sites.

Monitor INR and consider reducing dose or withholding depending on indication for use.

Seek advice if unexplained bruising or bleeding occurs

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References

1) http://www.ncbi.nlm.nih.gov/pubmed/15847359 accessed May 2015 2) http://www.medicines.org.uk/emc/medicine/23244/SPC Accessed June

2015 (Metformin SPC) 3) https://www.medicines.org.uk/emc/medicine/23944 accessed June

2015 (Digoxin SPC) 4) Renal Considerations in Angiotensin Converting Enzyme Inhibitor

Therapy, Anton C. Schoolwerth, MD, MSHA; Domenic A. Sica, MD; Barbara J. Ballermann, MD; Christopher S. Wilcox, MD, PhD, American Heart Association (AHA)

5) Opioid Safety in Patients With Renal or Hepatic Dysfunction, Author: Sarah J. Johnson, PharmD, Medical Editors: Lee A. Kral, PharmD, BCPS; Stewart B. Leavitt, MA, PhD, Medical Reviewers: Rebecca Hegeman, MD, Jignesh H. Patel, PharmD Bruce A. Mueller, PharmD, FCCP, Release Date: June 2007; Updated: November 30, 2007