1

Drug Information

for

Palliative Care

Updated August 2014

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Contents Introduction ............................................................................................................................... 5

Drug Monographs Amitriptyline .............................................................................................................................. 7

Bisacodyl .................................................................................................................................. 10

Carbamazepine ........................................................................................................................ 11

Citalopram................................................................................................................................ 13

Clonazepam ............................................................................................................................. 14

Clonidine .................................................................................................................................. 16

Codeine Phosphate .................................................................................................................. 17

Cyclizine ................................................................................................................................... 18

Danthron And Poloxamer ........................................................................................................ 19

Dexamethasone ....................................................................................................................... 20

Diazepam ................................................................................................................................. 22

Diclofenac ................................................................................................................................ 23

Docusate .................................................................................................................................. 24

Domperidone ........................................................................................................................... 25

Enoxaparin ............................................................................................................................... 26

Fentanyl ................................................................................................................................... 28

Fluconazole .............................................................................................................................. 30

Fluoxetine ................................................................................................................................ 31

Gabapentin .............................................................................................................................. 32

Glycerine & Thymol Mouthwash™ .......................................................................................... 33

Glycopyrrolate ......................................................................................................................... 34

Haloperidol .............................................................................................................................. 35

Hydrogen Peroxide Mouthwash 6% (20 Vol) .......................................................................... 36

Hyoscine Hydrobromide .......................................................................................................... 37

Hyoscine Butylbromide ............................................................................................................ 38

Ibuprofen ................................................................................................................................. 39

Ketamin (Ketalar™) .................................................................................................................. 40

Ketoconazole ........................................................................................................................... 41

Lax Sachets™ ............................................................................................................................ 42

Levomepromazine ................................................................................................................... 43

Loperamide .............................................................................................................................. 44

Lorazepam ................................................................................................................................ 45

Methadone .............................................................................................................................. 46

Methylphenidate ..................................................................................................................... 48

Metoclopramide ...................................................................................................................... 49

Metronidazole ......................................................................................................................... 50

Miconazole ............................................................................................................................... 51

Micolette Tm Enema.................................................................................................................. 52

Midazolam ............................................................................................................................... 53

Mirtazapine .............................................................................................................................. 54

Morphine ................................................................................................................................. 55

Naloxone .................................................................................................................................. 57

Naproxen.................................................................................................................................. 58

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Nortriptyline ............................................................................................................................ 59

Nystatin .................................................................................................................................... 60

Octreotide ................................................................................................................................ 61

Olanzapine ............................................................................................................................... 62

Omeprazole .............................................................................................................................. 63

Ondansetron ............................................................................................................................ 64

Oxybutynin ............................................................................................................................... 65

Oxycodone ............................................................................................................................... 66

Pamidronate Disodium ............................................................................................................ 68

Pantoprazole ............................................................................................................................ 69

Paracetamol ............................................................................................................................. 70

Paroxetine ................................................................................................................................ 71

Phenobarbitone ....................................................................................................................... 72

Menthol 0.5% In Dp Lotion ...................................................................................................... 73

Phenytoin ................................................................................................................................. 74

Prednisone ............................................................................................................................... 75

Promethazine ........................................................................................................................... 76

Quetiapine ............................................................................................................................... 77

Ranitidine ................................................................................................................................. 78

Risperidone .............................................................................................................................. 79

Saliva Substitute....................................................................................................................... 80

Senna........................................................................................................................................ 81

Sodium Acid Phosphate ........................................................................................................... 82

Spironolactane ......................................................................................................................... 83

Temazepam .............................................................................................................................. 84

Thioridazine ............................................................................................................................. 85

Tramadol .................................................................................................................................. 86

Tranexamic Acid ....................................................................................................................... 87

Triamcinolone 0.1% In Orabase ............................................................................................... 88

Valproate Sodium .................................................................................................................... 89

Warfarin ................................................................................................................................... 90

Zopiclone .................................................................................................................................. 91

Drugs by Symptom Anxiety ..................................................................................................................................... 92

Bleeding (haemorrhage) .......................................................................................................... 92

Constipation ............................................................................................................................. 92

Convulsions (seizures) .............................................................................................................. 92

Cough ....................................................................................................................................... 92

“Death Rattle” (Terminal Respiratory Congestion) ................................................................. 92

Delirium (confusion) ................................................................................................................ 92

Depression ............................................................................................................................... 93

Diarrhoea ................................................................................................................................. 93

Dyspnoea (breathlessness) ...................................................................................................... 93

Hiccup....................................................................................................................................... 93

Insomnia ................................................................................................................................... 93

Itch (pruritis) ............................................................................................................................ 93

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Mouth care .............................................................................................................................. 93

Nausea/vomiting...................................................................................................................... 94

Pain .......................................................................................................................................... 94

Restlessness (Terminal) – see pain, delerium, sedation ......................................................... 96

Sweating ................................................................................................................................... 96

Ulcer prophylaxis ..................................................................................................................... 96

Venous thromboembolism ...................................................................................................... 96

Wound care .............................................................................................................................. 96

Drugs by Generic Name .................................................................................................. 98

5

Drug Information

Introduction 1. Brands listed are the funded brands at time of writing.

2. Refer to Pharmaceutical Schedule and monthly updates. 3. *Specialist/Hospice* notation indicates that the drug should be prescribed initially by the hospice

specialist team – this is usually because use of the drug requires specialist monitoring or specialist input when converting from alternative medication, but may be because related to funding.

4. References for Drug Monographs:

BNF Volume 63 (March 2012)

Medsafe Data Sheets.

The Palliative Care Handbook 6th

Ed 2012

Drug Information Handbook, APhA, Lexi-Comp 2001-2002

Palliative Care Formulary online

MIMS online

MCH Formulary of Preferred Medicines with Prescribing Notes, 5th

Ed, 2005 Note: The Drug Monographs do not contain complete information about each drug – they are a brief summary only. Please refer to additional reference sources.

5. Undesirable Effects (PCF3 classification). We have used the term “undesirable effects” instead of

“adverse reactions”, in line with the recommendation from the European Commission.

Very Common: > 10%

Common: >1% to 10%

Uncommon: > 0.1% to 1%

Rare: > 0.1% to 0.01%

Very rare: < 0.01%

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Drug Information

Unlicensed Indications & Section 29 Some drugs used in palliative care are used for indications that they are not licensed for in New Zealand. Examples include:

Amitriptyline for neuropathic pain

Clonazepam for neuropathic pain

Baclofen for hiccups In order to use these drugs, they must be prescribed under Section 29 of the Medicines Act 1981. Section 29 allows prescribing of unlicensed/unregistered medications for individual patients. Practitioners prescribing these medications should:

Be aware of and comply with their obligations under Section 29 of the Medicines Act 1981 and otherwise under that Act and the Medicines Regulations 1984;

Be aware of and comply with their obligations under the Health and Disability Commissioner’s Code of Consumer Rights, including the requirement to obtain informed consent from the patient (PHARMAC recommends that Practitioners obtain written consent); and

Exercise their own skill, judgment, expertise and discretion, and make their own prescribing decisions with respect to the use of an unapproved medicine or a medicine for an indication for which it is not approved.

NOTE: Prescribing a Section 29 medicine:

Informed consent required from the patient

The dispensing pharmacy must give patient, medication, dose and prescriber information to the supplier, who then pass this information onto the MoH

A prescription is required.

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Drug Information

AMITRIPTYLINE (Arrow-Amitriptyline™, Amirol™, AmitripTM)

Class: tricyclic antidepressant (TCA), serotonin & noradrenaline re-uptake inhibitor (SNRI) Indication: depression, nocturnal enuresis in children Unregistered indications: co-analgesic in neuropathic pain (Section 29) Contraindications/cautions: arrhythmias, recent MI, epilepsy (lowers seizure threshold), urinary retention, severe hepatic dysfunction (reduce dose), hyponatraemia Undesirable effects: NB – small doses usually used in treating neuropathic pain so adverse effects are not usually major problems but may include: Common: anticholinergic - dry mouth, blurred vision, urinary retention, drowsiness (tolerance may

develop), constipation Less common: sweating, confusion, arrhythmias (and QT interval elongation, tachycardia, postural

hypotension (may double incidence of femoral fractures), serotonin syndrome, lowered seizure threshold. May cause photosensitivity reactions.

Interactions: Metabolised by CYP enzymes.

May have increased concentrations with CYP inhibitors e.g. fluconazole, fluoxetine, grapefruit juice, itraconazole, ketoconazole, metronidazole, haloperidol, paroxetine, omeprazole, miconazole and valproate sodium.

May have decreased concentrations with CYP inducers e.g. carbamazepine, dexamethasone, phenytoin, rifampicin, prednisone, phenobarbitone and cigarette smoke.

Risk of serotonin syndrome with other proserotonergic drugs - carbamazepine,tramadol, lithium, SSRIs e.g. fluoxetine, citalopram, paroxetine

Additive drowsiness with alcohol, benzodiazepines, opioids

Anticonvulsants - increased risk of seizures in epileptics

Increased risk of QT interval prolongation (cardiac adverse effect) with CYP inhibitors and flecainide, erythromycin, lignocaine, lithium & haloperidol Dosing:

Neuropathic Pain: 10-25mg orally at night (can consider increase to 50mg – 75mg at night, under specialist supervision but there appears to be a ‘therapeutic window’ for amitriptyline in some patients so increased doses may not give benefit) Syringe driver: not available Mechanism of action: Amitriptyline blocks the presynaptic re-uptake of serotonin and noradrenaline and thereby exerts antidepressant and analgesic effects. It also antagonizes muscarinic receptors, H1-receptors and ∞1-adrenergic receptors. Amitriptyline may also act as an NMDA-recpetor antagonist. Onset (pain): analgesic effect may manifest after 3 to 7 days; antidepressant effect after 2 to 4 weeks or longer Time to peak plasma concentration: 4 hours (po) Plasma half-life: 9-25 hours, active metabolite (nortriptyline) 15-39 hours Availability: Tab 10mg, 25mg, 50mg, fully funded

Notes:

May enhance morphine effects. A dose-response relationship has been shown for analgesic effect -increasing the dose of

amitriptyline above 50mg a day is unlikely to be of benefit in some patients (therapeutic window). Metabolised to nortriptyline which may be more tolerable.

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Drug Information

BACLOFEN (Pacifen™)

BNF Class: Skeletal muscle relaxant Indication: painful muscle spasm, spasticity Unlicensed Indications: hiccups Contraindications/cautions: contraindicated in active peptic ulceration (baclofen stimulates acid secretion). Caution in:

renal or hepatic impairment severe psychiatric disorders, confusional states or Parkinsons disease – exacerbations of these

conditions may occur epilepsy – lowering of convulsion threshold may occur history of peptic ulcer – as above diabetes, hypertonic bladder syndrome, respiratory impairment cerebrovascular disease, elderly (more sensitive to CNS effects)

Undesirable effects: Very Common: particularly at start of treatment, daytime sedation, drowsiness, nausea, muscle weakness Common: mental confusion, dizziness, ataxia, hallucinations, nightmares, headache, euphoria,

insomnia, depression, anxiety, agitation, tremor, nystagmus, convulsions, myalgia, respiratory or cardiovascular depression, hypotension, dry mouth, mild GI disturbances (retching, vomiting, constipation, diarrhoea), visual disturbances, rash, hyperhidrosis, frequency of micturition, enuresis, dysuria.

Interactions: May enhance hypotensive effect of ACE inhibitors and angiotensin-II antagonists, other antihypertensives and diuretics (adjust dose of antihypertensive); increased sedation & risk of respiratory depression when taken concomitantly with other agents acting on the CNS, synthetic opiates or alcohol; tricyclic antidepressants enhance muscle relaxant effect of baclofen; Dosing: Oral: start with 5mg bd to tds pc; increase by 5mg bd to tds every three days. Effective doses for hiccup are usually relatively low (5-10mg tds) but may be increased to 20mg tds if necessary and if tolerated. Take with food or milk Syringe Driver: N/A Mechanism of Action: Baclofen acts on the GABA-receptor, inhibiting the release of the excitatory amino acids glutamate and aspartate, principally at the spinal level and thereby decreases spasm in skeletal muscle. Baclofen relieves hiccup, possibly by a direct effect on the diaphragm. Bioavailability: >90% po Onset of Action: 3 to 4 days (onset of therapeutic effect varies from hours to weeks (individual variation). Time to peak plasma conc: 0.5 to 3 hours after oral administration Plasma half-life: 3.5 hours (4.5 hours in the elderly) Duration of Action: 6 to 8 hours Dose adjustment in renal impairment: Dose reduction required in renal impairment as excreted principally unchanged in the urine; 75% of dose excreted via kidneys, 25% via faeces.

Dose adjustment in hepatic impairment: Moderate hepatic insufficiency has no major effect on pharmacokinetics of baclofen. No information available in severe hepatic impairment. Availability: Tab, 10mg, fully funded.

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Drug Information

BENZYDAMINE (Difflam Mouthwash™)

Class: local analgesic Indication: Benzydamine mouthwash or spray may be useful in palliating the discomfort associated with a variety of painful inflammatory conditions of the oropharynx. It may also be useful in reducing the discomfort of post-irradiation mucositis. Unlicensed Indications: Contraindications/cautions: Care if drinking hot drinks after use. Undesirable effects: Occasional numbness or stinging; Rarely hypersensitivity reactions Interactions: None recorded Dosing: Rinse or gargle, using 15ml (diluted with water if stinging occurs) every one and a half to 3 hours as required. BNF does not recommend use in children < 12 years, but spray or lozenges are available (not funded) Syringe Driver: N/A Mechanism of Action: Local analgesia Onset: Immediate Duration: Up to one and a half hours Availability: 500ml Partially funded Notes:

Some patients find the full-strength mouthwash causes some stinging and, for them, it should be diluted with an equal volume of water. Care if drinking hot drinks after use.

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Drug Information

BISACODYL (Lax-Tabs™, Dulcolax™)

Class: laxative - stimulant Indication: constipation Unregistered indications: Contraindications/cautions: acute abdominal pain, intestinal obstruction Undesirable effects: Common: Abdominal cramps, diarrhoea, local rectal inflammation (suppositories) Interactions: May antagonise effects of antispasmodics e.g. hyoscine butylbromide Dosing: Oral: Tablet 5-10mg at night or twice a day S/C: Not available Rectal: Suppository 10mg daily Syringe driver: not available Mechanism of action: Stimulates colonic activity via nerves in the intestinal mucosa Onset of action: Oral: 6-12 hours Rectal: 20-60 minutes or up to 3 hours Availability: Tab 5mg Fully funded Lax-Tabs™ Supp 5mg Fully funded Dulcolax™ Supp 10mg Fully funded Dulcolax

TM

Notes:

May be useful in opioid induced constipation especially in combination with a softener.

Warm suppository in hand before removing foil wrapper. Insert pointed end first. Do not coat suppository with lubricant.

Bisacodyl suppositories occasionally cause faecal leakage, even after a successful evacuation

Do not take tablet with milk or within half an hour of taking antacids

11

Drug Information

CARBAMAZEPINE (Tegretol™, Tegretol CR™)

Class: anticonvulsant Indication: Epilepsy, neuropathic pain, mood stabiliser Unregistered indications: Contraindications/cautions: Bone marrow depression, severe hepatic dysfunction (reduce dose); AV conduction abnormalities; cardiac disease; history of haematological reactions to other drugs; glaucoma. Undesirable effects: Common: dry mouth, diarrhoea, constipation, dizziness, nausea, ataxia (dose related), blurred vision,

vomiting, rash, confusion (dose related), blood dyscrasias, increased LFTs Interactions:

Metabolised by CYP enzymes.

May have increased concentrations with CYP inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, miconazole and valproate sodium, grapefruit juice.

May have decreased concentrations with CYP inducers e.g. dexamethasone, phenytoin, prednisone. rifampicin

Induces it’s own metabolism and may decrease concentrations of drugs metabolised by CYP enzymes e.g. amitriptyline, clonazepam, dexamethasone, fentanyl, ketoconazole, methadone, mexiletine, miconazole, midazolam, omeprazole, prednisone, risperidone, tramadol, warfarin, phenobarbitone and phenytoin

Increased risk of serotonin syndrome with other proserotonergic drugs e.g. fluoxetine, amitriptyline, lithium, tramadol

Dosing: Pain (neuropathic): Oral: 100 - 600mg twice a day (withdraw slowly).

Start with 100-200mg once or twice daily. Titrate to pain, increasing by 100-200mg gradually according to response to a maximum of 1.2g to 1.6g per 24 hours in divided doses. Usual dose 200mg 3 to 4 times daily.

S/C: not available Rectal: not available Syringe driver: not available Mechanism of action: In pain still unknown. May be related to reduction in nerve cell excitability. Peak concentrations: Normal release: 4-5 hours Syrup: 1.5 hours CR: 3-12 hours Onset (pain): 3 - 7 days

Availability: Tab 200mg, 400mg Fully funded Tab CR 200mg, 400mg Fully funded Syrup 100mg/ 5ml Fully funded

Notes:

Monitor plasma concentrations (plasma concentration for optimim response as an anti-epileptic, 20 to 42 umol/l – MCH).

Carbamazepine should be discontinued or the dose decreased if the white cell count falls below 3000/mm3 or the neutrophil count below 1000/mm3. (MCH)

Co-analgesic often used with opioids in the treatment of neuropathic pain.

May be used in neuropathic pain where tricyclic antidepressants have failed or in combination with tricyclic antidepressants.

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5.3 Drug Information Continued Learning

Gabapentin may be a more effective anticonvulsant in neuropathic pain. May be taken with or without food. Increased dosage may be required if switching from conventional tablets to CR. Controlled

release tablets are best suited to twice daily dosage regimens.

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Drug Information

CITALOPRAM (Arrow-Citalopram™)

Class: Antidepressant - SSRI (Selective Serotonin Re-uptake Inhibitor) Indication: Depressive illness, panic disorder Unregistered indications: Anxiety (chronic), neuropathιc pain Contraindications/cautions: Hepatic impairment, epilepsy (caution), bleeding disorders (decreased platelet aggregation), caution in cardiac disease, abrupt withdrawal Undesirable effects: Common: nausea, vomiting, dyspepsia, sweating, tremor, diarrhoea (excessive serotonιn),

constipation, somnolence Less common: dry mouth, cough, postural hypotension, tachycardia, amnesia, taste disturbance, visual

disturbances, prurιtιs, hyponatraemιa, urinary retention Interactions:

CYP enzymes - metabolised by CYP 2C19.

May have increased concentrations with 2C19 inhibitors e.g. fluconazole, fluoxetιne, omeprazole and valproate sodium.

May have decreased concentrations with 2C19 inducers e.g. carbamazepιne, dexamethasone and phenobarbitone.

Risk of serotonιn syndrome with other proserotonergιc drugs e.g. tricyclic antidepressants, carbamazepιne.

Increased risk of bleeding with warfarin. Dosing: Oral: 10-40mg once a day S/C: Not available, Rectal: Not available Syringe driver: N/A Mechanism of action: Blocks the reuptake of serotonιn Onset: Depression: 1-2 weeks Anxiety or pain: 3-7 days Peak response: 5-6 weeks Availability: Tab 20mg - Fully funded Notes:

May not inhibit CYP2D6 to as great an extent as other SSRls e.g. fluoxetιne, paroxetιne so less likely to interact with drugs that are metabolised by CYP2D6 e.g. codeine, haloperidol, mexiletine, ondansetron.

Antidepressive effect may not be evident for 2-4 weeks

Maximum of 20mg/day for patients with hepatic impairment.

Max of 20mg/day for patients >60 years old.

14

Drug Information

CLONAZEPAM (Paxam™, Rivotril™)

Class: anticonvulsant - benzodiazepine Indication: epilepsy, convulsions Unregistered indications: Sedation, anxiety, panic disorder, restless leg syndrome, neuropathic pain, terminal agitation, subcutaneous injection/infusion Contraindications/cautions: Avoid sudden withdrawal, respiratory depression, sleep apnoea syndrome; caution in hepatic & renal impairment & elderly Undesirable effects: Common: fatigue, drowsiness (at higher doses) Uncommon: respiratory depression (rare), incontinence, co-ordination problems, disinhibition, increase

in salivation, confusion Interactions:

Metabolised by CYP3A4 enzymes to inactive metabolites.

May have increased concentrations with 3Α4 inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole and valproate sodium.

May have decreased concentrations with 3Α4 inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin and prednisone.

Additive CNS effect with other CNS depressants e.g. other benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and opioids.

Dosing: Sedation, anxiety, agitation, restless leg syndrome, neuropathic pain: Oral: start with 0.5mg nocte; titrate to response (See PCF4) S/C: 1-8mg/24 hours (terminal sedation) Rectal: Not available Syringe driver: See syringe driver compatibility table. Mechanism of action: Clonazepam is a typical benzodiazepine with GABA-potentiating actions in the CNS, notably spinal cord, hippocampus, cerebellum & cerebrum. Clonazepam reduces neuronal activity at these sites. Onset: 5-10 minutes (sc); 20-60 minutes (oral) Half life: mean 30 hours (20-40 hours) Availability: Tab 0.5mg, 2mg - Fully funded Paxam

TM

Oral drops 2.5mg/ml, 10ml - Fully funded RivotrilTM

Inj l mg/ml 1 ml - Fully funded Rivotril

TM

Notes:

Long acting benzodiazepine are difficult to titrate to response.

Benzodiazepines may reduce dyspnoea by their anxiolytic and sedative effects.

15

Drug Information

Approximate equivalent oral anxiolytic-sedative doses:

Drug Dose

Diazepam 5mg

Lorazepam 0.5mg

Clonazepam 0.5mg

Temazepam 10mg

Midazolam 7.5mg

Triazolam 0.25mg

Pharmacological properties of benzodiazepines and other hypnotics

Drug Anxiolytic Night sedation Muscle relaxant Anti-convulsant

Diazepam +++ + +++ ++

Lorazepam +++ ++ + +

Clonazepam ++ + + +++

Temazepam + +++ + +

Midazolam + +++ + +++

Zopiclone - +++ - -

16

Drug Information

CLONIDINE (Catapres™, Dixarit™)

Class: Alpha2-adrenergic agonist Indication: hypertension, migraine prophylaxis, menopausal flushing Unregistered Indications: diabetes-associated diarrhoea, and in combination with opiates, for treatment of severe pain in refractory cancer patients (most effective in neuropathic pain); synergistic analgesic effect with opioids. (PCF3) Contraindications/cautions: hypersensitivity to clonidine; cardiac conduction defects; recent MI; stroke, peripheral vascular disease; may precipitate depression in susceptible patients. Undesirable effects: Very Common: Sedation & dry mouth (initially), dizziness, transient pruritis & erythema (TD route) Common: Headache, fatigue, lethargy, depression (longterm use), nervousness, nocturnal restlessness,

peripheral vasoconstriction, nausea, vomiting, anorexia, constipation, Na & water retention, nocturia, sexual dysfunction.

Interactions:

Decreased effect: tricyclic antidepressants antagonise hypotensive effects of clonidine;

Increased effect: concurrent use with antipsychotics, narcotic analgesics may produce additive hypotensive effects;

Clonidine can increase cyclosporin serum levels; may decrease symptoms of hypoglycaemia with oral hypoglycaemics; tricyclic antidepressants may also enhance the hypertensive response associated with abrupt clonidine withdrawal.

Dosing: Tablets 150mcg Transdermal patches applied one every 7 days. Syringe Driver: N/A Mechanism of Action: Stimulates alpha-2-adrenoreceptors in the brain stem, thus activating an inhibitory neuron, resulting in reduced sympathetic outflow, producing a decrease in vasomotor tone and heart rate; epidural clonidine may produce pain relief at spinal presynaptic and postsynaptic alpha2-adrenoreceptors by preventing pain signal transmission. Pain relief occurs only for the body regions innervated by the spinal segments where analgesic concentrations of clonidine exist. Onsetof action: 30-60 minutes (oral) Time to peak plasma conc: 1.5-5 hours (oral) Plasma half life: 12-16 hours. Duration: Oral: 8-24 hours Metabolism/Excretion: About 50% of dose is excreted unchanged by kidneys; remainder is metabolised by liver to inactive metabolites. Accumulation occurs in renal impairment – half-life may extend up to 40 hours. Availability: Tabs 150mcg - fully funded Transdermal patches 0.1mg, 0.2mg & 0.3mg/day - fully funded on prescription only; Inj 150mcg/ml, 1ml – fully funded. Dose adjustment in renal impairment: Half life in renal impairment 18-40 hours; Cr Cl <10ml/min, administer 50% to 75% of dose initially. Not dialysable.

17

Drug Information

CODEINE PHOSPHATE (Codeine phosphate tabs) (Codalgin™, Panadeine™, RelieveTM)

Class: analgesic – opioid, about 1/10 as potent as morphine Indication: mild to moderate pain (step 2 in the WHO analgesic ladder), cough, diarrhoea Unregistered Indication: Contraindications/cautions: avoid use with other opioid analgesics Undesirable effects: as for morphine. Very constipating. Interactions:

CYP enzymes - metabolised by CYP 2D6.

May have increased concentrations of codeine and decreased concentrations of morphine (active metabolite) with 2D6 inhibitors e.g. fluoxetine, haloperidol and paroxetine (reduces analgesic activity significantly) - additive CNS effects with other CNS depressants e.g. benzodiazepine (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and other opioids.

Metoclopramide/domperidone-may inhibit antidiarrhoeal effects Dosing: Pain, cough and diarrhoea: Oral: 15 - 60mg 4-6 hourly (Max 240mg in 24 hours) S/C: Not recommended - use other opioid instead Rectal: Not available Syringe driver: Not used Mechanism of action: Metabolised to morphine and other active metabolites. Significant interindividual variability in production of morphine and therefore response. Onset of action: 30-60 minutes (analgesia); 1-2 hours (anti-tussive) Time to peak plasma concentration: 1-2 hours Plasma Half-life: 2.5 to 3.5 hours Duration: 4-6 hours Availability: Tab 15mg, 30mg, 60mg - fully funded Notes:

Combination products not recommended. 10% of dose is converted to morphine in "normal

" metabolisers i.e. 60mg codeine = 6mg morphine. May

be as little as 2% converted in slow metabolisers 5-10% of Caucasian population may be unable to metabolise it to morphine. Combination with other opioids is illogical. Dihydrocodeine slow release is available (though not often used in palliative care).

18

Drug Information

CYCLIZINE (Nausi-calm™, Marzine™)

Class: antihistaminic antimuscarinic antiemetic Indication: nausea/vomiting (including motion sickness), vertigo Unregistered indications: Subcutaneous injection/infusion Contraindications/cautions: Prostatic hypertrophy, narrow angle glaucoma, severe heart failure Undesirable effects: Common: drowsiness, restlessness, dry mouth, blurred vision, constipation, headache Uncommon: insomnia, hallucinations (more common in elderly), arrhythmias Interactions: Additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and other opioids. Dosing: Oral: 50 tds and prn (cyclizine hydrochloride) S/C: 75-150mg/ 24 hours via scp (typically 100mg) (cyclizine lactate) well diluted. Rectal: ,Not available Syringe driver: See syringe driver compatibility table. Mechanism of action: Acts on the histamine receptors in the vomiting centre in the CNS and has anticholinergic properties. Peak concentration: Approx 2 hours Availability: Tab 50mg - fully funded Inj 50mg/ml - fully funded. Notes:

Although a theoretical interaction with prokinetic antiemetics prokinetics stimulate the gut while cyclizine slows it down) use together is common and may be justified on the basis of differential effect on central receptors.

19

Drug Information

DANTHRON and POLOXAMER (Pinorax™)

Class: laxative - stimulant with faecal softener Indication: constipation - opioid induced and in the elderly; danthron with poloxamer is only approved for the prevention or treatment of constipation in the terminally ill. Unregistered indications: Contraindications/cautions: acute abdominal pain, intestinal obstruction Undesirable effects: Common: Abdominal cramps, diarrhoea, perianal irritation, pink or red urine/perianal skin

(can lead to excoriation in incontinent patients) Uncommon: Atonic colon (on prolonged use), hypokalaemia (GI loss) Interactions: May antagonise effects of antispasmodics e.g. hyoscine butylbromide Dosing: Oral: Opioid induced (prophylaxis and treatment): Co-danthromer Forte - start with 5ml

nocte, increase to 10ml once or twice a day or 20ml nocte, according to response S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Stimulates colonic activity via nerves in the intestinal mucosa (danthron) and increases fluid uptake by stools thus softening them (poloxamer). Onset: Oral: 6-12 hours Availability: Oral susp: funded (to be delisted January 2015) Only approved for the prevention or treatment of constipation in the terminally ill Notes:

Shake well before use. May cause a pink or red colouring of urine. Take plenty of fluids.

20

Drug Information

DEXAMETHASONE (Dexamethasone™ (Douglas), Dexamethasone™ (Biomed) Dexamethasone Hameln)

Class: corticosteroid - glucocorticoid

Indication: cerebral oedema (raised intracranial pressure), allergy, anaphylaxis, nausea & vomiting with chemotherapy

Unregistered indications: nausea/vomiting, inflammation in gastrointestinal obstruction, sweating, itch, hiccup, pain including bone pain, dyspnoea (lymphangitis), liver capsule pain, tenesmus, subcutaneous injection/infusion, spinal cord compression, nerve compression, SVC obstruction, radiation-induced inflammation, improve appetite, enhance sense of wellbeing

Contraindications/cautions: infections, GI bleeding, diabetes, psychotic illness

Undesirable effects:

Common: Insomnia (less if single dose in the morning) Sodium/ fluid retention, K loss, hypertension, GI ulceration, delayed wound healing, thinning of skin (on prolonged use), muscle weakness (proximal myopathy), Cushing's syndrome, weight gain, paranoid psychosis, depression, delirium, hyperglycaemia, osteoporosis

Interactions: Metabolised by CYP3A4. May have increased concentrations with 3Α4 inhibitors e.g. fluconazole, fluoxetine,

ketoconazole, metronidazole and valproate sodium. May have decreased concentrations with 3Α4 inducers e.g. carbamazepine, phenobarbitone,

phenytoin and prednisone. Induces 3Α4 and 2C and may have decreased concentrations of drugs metabolised by them e.g.

amitriptyline, clonazepam, fentanyl, ketoconazole, methadone, miconazole, midazolam, omeprazole, phenytoin, prednisone, risperidone, tramadol and warfarin.

increased risk of GI bleed/ulceration when given with NSAIDs Dosing:

The oral bioavailability of dexamethasone is 80% therefore the conversion ratio from oral to subcut/intravenous is 1:

0.5 – 1mg / day To decrease irritation at the infusion site

2 – 4 mg / day Increase appetite

Non-specific pain

Anti-emetic

4 – 8 mg / day Co-analgesic in:

Nerve compression pain

Pain from:

Hepatomegaly

Intestinal obstruction

Bone pain

Radiotherapy induced inflammation

> 8 mg / day Cerebral tumours

Raised intracranial pressure

Spinal cord compression

SVC obstruction

Large airways obstruction

Ref: Waitemata DHB Medicine & Infusion Protocols

21

Drug Information

Oral: 4-32mg in 24 hours - see notes below

S/C: 4-16mg/24 hours

Rectal: Not available

Syringe driver: see syringe driver compatibility table. – recommended diluent is water for injection. It should be added last to an already dilute combination of drugs in order to reduce the risk of precipitation

Mechanism of action:

Decreases inflammatory response thought to be via induction of lipocortin, an anti-inflammatory protein.

Onset: 8-24 hours IM

Peak plasma conc: 1-2 hours po

Plasma half-life: 4.5 hours

Duration of Action: 36-54 hours

Availability:

Tab l mg, 4mg - fully funded - specialist recommendation required

Oral liquid 1mg/ml - fully funded for children <12 years only

Inj 4mg/ml lml & 2ml - fully funded

Notes: 0.75mg dexamethasone has an equivalent anti-inflammatory effect to 5mg prednisone or 20mg

hydrocortisone (see table). On discontinuation decrease dose slowly (taper) unless the patient has been taking it for less than five

days in which case dose tapering is not necessary. Alteration in mood not usually seen below 6mg dexamethasone (40mg prednisone) per day. Corticosteroid induced insomnia responds to benzodiazepines (e.g. temazepam) but not to zopiclone. Corticosteroid induced mood disorder is usually depression and rarely mania. Once daily dose in the morning after food, or twice daily (morning and noon) where higher dose given or

GI s/e occur. Dosing earlier in the day helps to minimise any insomnia If diabetic monitor blood sugars The use of 0.5mg -1mg dexamethasone in a syringe driver may reduce the risk of irritation at the

subcutaneous site.

Approximate equivalent ant-inflammatory doses of corticosteroids

Hydrocortisone

20mg

Prednisone

5mg

Prednisolone

5mg

Methylprednisolone

4mg

Dexamethasone

0.75mg

Ref: PCF 4

22

Drug Information

DIAZEPAM (Arrow-Diazepam™, Stesolid™)

Class: Anxiolytic, anticonvulsant, benzodiazepine, sedative Indication: In palliative care, used rectally to treat convulsions due to cerebral tumours or uraemia. Also used in anxiety disorders, muscle spasm. Unregistered Indications: Contraindications/cautions: Hypersensitivity to diazepam; may be a cross-sensitivity with other benzodiazepines; use with caution in those on other sedative medications; acute or severe pulmonary insufficiency, sleep apnoea, severe liver disease, renal impairment Undesirable effects: Common: Drowsiness, muscle flaccidity, unsteadiness Less common: Paradoxical effects (insomnia, anxiety, excitement, hallucinations) have been reported Interactions:

Carbamazepine, rifampicin may enhance metabolism of diazepam & decrease its therapeutic effect. Amiodarone, cimetidine, ciprofloxacin, clarithromycin, clozapine, CNS depressants, diltiazem, digoxin,

erythromycin, fluconazole, fluoxetine, fluvoxamine, isoniazid, metronidazole, miconazole, nefazodone, omeprazole, phenytoin, rifampicin, valproate and verapamil may increase the serum level and/or toxicity of diazepam (enhanced & more prolonged effect)

Dosing: Anxiety: 2-10mg po Convulsions: 5-10mg rectally every 10 to 20 minutes, up to 30mg in 8-hour period. Seek advice from

specialist team at hospice if convulsions do not resolve. Syringe Driver: N/A Mechanism of Action: Depresses all levels of CNS, probably through increased action of GABA which is a major inhibitory transmitter in the brain. Onset of action: 15 min PO Time to peak plasma conc: 30-90 min PO Plasma half-life:24-48 hours (metabolite nordiazepam 48-120 hours) Duration: 3-30 hours; can be prolonged in elderly & in hepatic impairment Availability: Tabs 2mg, 5mg, 10mg – fully funded 1 month only on Rx

Rectal tubes 5mg & 10mg – fully funded Injection 5mg/ml – only funded on PSO

Dose adjustment in renal impairment:

Dose adjustment in hepatic impairment: Metabolised in liver by CYP enzymes; reduce dose in severe hepatic impairment. Notes

Additive sedative effect with alcohol

Grapefruit juice may increase serum levels & toxicity

23

Drug Information

DICLOFENAC (Voltaren™, Apo-DiclaxTM, Cataflam™, Diclax™) (Voltaren™ (suppositories and injection))

Class: non-steroidal anti-inflammatory drug (NSAID) Indication: pain & inflammation, post-operative pain Unregistered indications: Subcutaneous injection/infusion, sweating, neoplastic fever Contraindications/cautions: Active peptic ulceration, hypersensitivity to aspirin or other NSAIDs (urticaria,asthma, angioedema), renal impairment, severe CHF. Undesirable effects: Common: headache, dizziness, oedema, nausea, indigestion, abdominal distension, pain or cramp,

flatulence, diarrhea, constipation, pruritis, rash Less common: nephrotoxicity, hepatitis, hypertension, tinnitus, proctitis (rectal administration).

Inhibits platelet aggregation- may prolong bleeding time. Interactions:

Metabolised by CYP2C9 enzymes. May have increased concentrations with 2C9 inhibitors e.g. fluconazole, fluoxetine, ketoconazole,

metronidazole, miconazole and valproate sodium. May have decreased concentrations with 2C9 inducers e.g. dexamethasone, phenobarbitone and

phenytoin ACE inhibitors (e.g. enalapril) increase risk of renal toxicity and hyperkalaemia Increased risk of gastro-intestinal bleed with corticosteroids -concentrations of lithium, digoxin,

methotrexate and warfarin may be raised – monitor. May reduce effects of diuretics (e.g. frusemide) and antihypertensives (e.g. propranolol)

Dosing: Oral: 50-150mg per day in three divided doses for normal release and two divided doses

(sometimes just one) for long acting preparations. S/C: Inj available but not for sc injection as too irritant. Try tenoxicam. Rectal: As for normal release oral Syringe driver: not recommended Mechanism of action: Inhibits prostaglandin synthesis. Prostaglandins are involved in inflammation and pain. Onset of action: 20-30 minutes Peak effect: 20 minutes (IM); 2.5 hours (oral SR); 20-60 minutes (oral normal release) Duration of action: oral (normal release): 6-8hours Plasma Half-life: 1-2 hours Availability: Tab EC 25mg, 50mg (normal release) - fully funded Tab dispersible 50mg (normal release) - partially funded Tab long acting 75mg, 100mg - fully funded Supp 12.5mg, 25mg, 50mg, 100mg - fully funded

Inj 25mg/ml, 3ml - fully funded Notes:

Co-analgesic often used with opioids in the treatment of bone and soft tissue pain. NSAID of choice in palliative care. Take SR tablets with food. Regular tablets should be taken before meals except when used long

term or where there is a history of GI ulceration. Patients at risk of gastro-intestinal bleeds should be prescribed gastric protection (e.g.

omeprazole) prophylactically. Avoid if severe renal or hepatic impairment.

24

5.3 Drug Information Continued Learning

DOCUSATE (Laxofast™, Laxsol™ (in combination with sennosides))

Class: laxative – faecal softener Indication: constipation Unregistered Indications: Contraindications/cautions: Acute abdominal pain Undesirable effects: Less common abdominal cramps, bitter taste Interactions: Decreased clinical effect of antispasmodics (eg hyoscine butylchloride) may occur with concomitant docusate Dosing: Oral: 100mg to 480mg daily (with senna 1 to 2 tablets at night – max 4 tablets) Sc: not available Rectal: 1 as required Syringe Driver: not available Mechanism of Action: thought to increase intestinal secretions and facilitate their movement into faeces producing softer stools Onset : 1 – 3 days Duration: Availability:

Tablet 50mg, 120mg - fully funded (Laxsofast™) Tablet 50mg (with 8mg senna) - fully funded (Laxsol™) Enema 18% - fully funded (Coloxyl™) Dose adjustment in renal impairment: Dose adjustment in hepatic impairment: Notes:

As docusate has some stimulant action it should be avoided in complete intestinal obstruction as should all stimulant laxatives

Not laxative of choice in opioid induced constipation as a single agent but useful in combination with a stimulant. (eg Laxsol™) although giving a softener and a stimulant as separate tablets may be more effective

25

Drug Information

DOMPERIDONE (Prokinex™) (see below)

Class: antiemetic - prokinetic, dopamine antagonist Indications: Nausea, vomiting, dysmotility dyspepsia, gastro-oesophageal reflux Unregistered indications: Contraindications/cautions: Complete intestinal obstruction ; prolactinoma ; GI haemorrhage or perforation Undesirable effects: Very common: hyperprolactinaemia, breast tenderness, transient colic Common: pruritis, rash, cramp, headache, dizziness Interactions:

Prokinetic effect may be reduced by anticholinergic drugs e.g. amitriptyline, hyoscine Increased effect(due to increased blood concentrations) may occur with some CYP enzyme inhibitors eg

fluconazole, fluoxetine, grapefruit juice, itraconazole, ketoconazole, metronidazole, sod valproate Decreased effect may occur with some CYP enzyme inducers eg carbamazepine, phenobarbitone,

phenytoin, prednisone, rifampicin Dosing: Oral: 10-20mg three to four times a day, 15-30 mins before food S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Similar to metoclopramide- blocks dopamine receptors in the upper gastrointestinal tract, chemoreceptor trigger zone (CTZ) and the CNS (minimal effect on CNS therefore less likely to cause extrapyramidal side-effects than metoclopramide) Peak concentration: 30-110 minutes Availability: Tab 10mg - Fully funded. Notes:

Main advantage over metoclopramide is lack of extrapyramidal side-effects (does not cross BBB) but not available as injection.

Dual-action anti-emetic – acts on dopamine receptors in CTZ and on D-2 receptors at the gastro-oesophageal and gastroduodenal junctions.

Useful in nausea and vomiting associated with gastric stasis. Anti-emetic of choice in Parkinsons disease. Plasma half-life is increased by up to 50% in renal failure, but plasma concentrations do not increase;

renal elimination is a minor route. Maximum absorption in acid environment – absorption reduced by PPIs and antacids

26

Drug Information

ENOXAPARIN (Clexane™)

Class: anticoagulant – low molecular weight heparin Indication: Prophylaxis and treatment of venous thromboembolism, unstable angina, MI Unregistered Indications: Duration of more than 30 days treatment Contraindications/cautions: Heparin allergy, active bleeding, recent haemorrhagic stroke, low platelets, renal impairment(adjust dose), spinal/epidural medication, prosthetic heart valve, history of gastrointestinal ulceration/bleed Undesirable effects: Very common: haemorrhage, haematoma, elevated LFTs Common: allergic reactions, skin necrosis, thrombocytopenia Interactions: increased effect may occur with other drugs that decrease blood clotting eg aspirin, clopidogrel,

warfarin, heparin increased risk of bleeding when combined with NSAIDS decreased effect may occur with haemostats eg tranexamic acid and phytomenadione (Vitamin K)

Dosing: Oral: not available S/c: treatment (of DVT etc) 1.5mg/kg once a day or 1mg/kg twice a day (lower in the obese) Prophylaxis 20mg to 40mg once or twice a day Syringe Driver: not available Mechanism of Action: has high anti-Xa activity Peak Effect: 3 to 5 hours post injection Duration: Availability: Syringe: 20mg/0.2ml, 40mg/0.4ml, 60mg/0.6ml, 80mg/0.8ml, 100mg/1ml, 120mg/0.8ml, 150mg/1ml 1 Aug 09 Funded on Special Authority application for the treatment of venous thromboembolism where the patient has a malignancy (can be scripted by GP) Dose adjustment in renal impairment: caution in moderate impairment, dose adjustment necessary in severe renal impairment

Standard Dosing Severe renal impairment

1 mg/kg SC twice daily 1 mg/kg SC once daily

1.5 mg/kg SC once daily 1 mg/kg SC once daily

Acute STEMI patients < 75 years of age

30 mg single IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC twice daily

30 mg single IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC once daily

Acute STEMI patients > 75 years of age

0.75 mg/kg SC twice daily without initial bolus

1 mg/kg SC once daily without initial bolus

Ref: Medsafe data sheet

27

Drug Information

The following dosage adjustments are recommended for prophylactic dosage ranges:

Normal Dosing Severe renal impairment

40 mg SC once daily 20 mg SC once daily

20 mg SC once daily 20 mg SC once daily

Ref: Medsafe data sheet

Dose adjustment in hepatic impairment: Caution in patients with hepatic impairment

Notes: As the coagulation ability of cancer patients is altered it may be that the low molecular weight heparins are a better choice in these patients than warfarin

28

Drug Information

FENTANYL (Mylan Fentanyl patch, Fentanyl Citrate injection)

Class: analgesic – strong opioid Indication: Moderate to severe chronic pain including cancer Unregistered indications: morphine intolerance Contraindications/cautions: Fentanyl hypersensitivity/ allergy (past nausea or hallucinations with opioids are not contraindications) Undesirable effects: See morphine. Less constipating (halve dose of laxatives when converting from morphine then titrate to need), less sedating and less emetogenic than other opioids (probably due to lipophilicity of fentanyl). Occasional skin irritation with Transdermal patch. Interactions:

CYP enzymes - metabolised by CYP3A4. May have increased concentrations with 3Α4 inhibitors e.g. fluconazole, fluoxetine, ketoconazole,

metronidazole and valproate sodium. May have decreased concentrations with 3Α4 inducers e.g. carbamazepine, dexamethasone,

phenobarbitone, phenytoin and prednisone. Additive CNS depression with other CNS depressants e.g. benzodiazepines (e.g. lorazepam),

phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and other opioids Dosing: S/C: 50-300mcg in 24 hours Transdermal Patch: 25 - 100mcg/hour (each patch lasts for 3 days) Syringe driver: See compatibility chart. Mechanism of action: Stimulates μ opioid receptors in the CNS and GIT. Onset of action: TD – 3-23 hours Time to peak plasma conc: TD: 24 – 72 hours Plasma Half-life: TD – 13-22 hours Duration: TD: 72 hours (48 hours for some patients) Availability: Patches: 12.5mcg/hr,25mcg/hr, 50mcg/hour, 75mcg/hr, 100mcg/hour - Fully funded. Injection: 100mcg/2m1, 500mcg/ 10ml. - fully funded. Controlled drug form required. Notes:

Conversion: morphine (po) : fentanyl(sc/patch) = 150:1 i.e. 10mg morphine po = 66 micrograms of fentanyl sc

Oral morphine Fentanyl patch (mg/ 24 hours) (mcg/hour)

<60 12.5 60-134 25 135-224 50 225-314 75 315-404 100 405-494 125 495-584 150 585-674 175 675-764 200

Note: All conversions must be overseen by Hospice Specialist please.

29

Drug Information

Notes on Fentanyl patches

Unsuitable for opioid-naïve patients – dose needs to be titrated up before starting Use morphine or s/c fentanyl for rescue, and to titrate up in opioid naïve patient If patient is febrile or has a heat pad near the patch the rate of absorption from the patch may

be increased. Symptoms of acute toxicity include decrease in respiratory rate, mental status, blood pressure.

Give naloxone 2mg IV and repeat as required (max 10mg). Consult hospice specialist team. The patches leave a depot in the skin which will carry on releasing fentanyl on removal (at least 17 hours for concentrations to drop by 50%).

Dose adjustments for the patch should usually be done every 3 days. To achieve dose of 125mcg/hour, use one 100mcg patch and one 25mcg patch, for example. If patch comes unstuck dispose of patch safely and replace with a new one. Fold used patches so adhesive side adhere to itself, wrap and dispose carefully

30

Drug Information

FLUCONAZOLE (Fluconazole™, Ozole™, Diflucan™)

**Specialist/Hospice**

Class: antifungal - triazole Indication: fungal infections Unregistered indications: Contraindications/cautions: Renal impairment, hepatic impairment Undesirable effects: Common: Gastrointestinal upset (nausea, vomiting, dyspepsia, abdominal pain, diarrhea),

headache, dizziness, rashes, pruritis, hypokalaemia

Interactions:

CYP enzymes - inhibits CYP2C and 3Α4.

May increase concentrations of carbamazepine, diclofenac, ibuprofen, naproxen, phenytoin, warfarin, tenoxicam, amitriptyline, clonazepam, dexamethasone, fentanyl, methadone, miconazole, midazolam, omeprazole, prednisone, risperidone and tramadol.

May antagonise effect of amphotericin. Dosing: Oral: Systemic candidiasis oropharyngeal candidiasis: 50-100mg once a day for 7 days;

prophylaxis in malignancy 50mg once a day Vaginal candidiasis: 150mg as a single dose Cryptococcal infections: 200-400mg once a day for 7 days S/C: Not usually used Rectal: Not available Syringe driver: not applicable Mechanism of action: Inhibits fungal cell membrane formation Availability: Cap 50mg, 150mg, 200mg - fully funded if endorsed retail pharmacy – specialist. Inj 2mg/ml 50ml - not funded – Section 29 Susp 50mg/ 5ml, 35ml -funded – Special Authority

Notes:

May be less likely to interact with other CYP metabolised drugs (see above) than ketoconazole. Useful in severe or recurrent fungal infections. Consult hospice specialist; requires specialist recommendation for funding.

31

Drug Information

FLUOXETINE (Arrow-Fluoxetine™)

Class: antidepressant- SSRI (Selective Serotonin Re-uptake Inhibitor) Indication: Depression, bulimia nervosa, obsessive-compulsive disorder Unregistered indications: neuropathic pain, anxiety (chronic) Contraindications/cautions: Epilepsy, bleeding disorders (decreases platelet aggregation); cardiac disease, diabetes, hepatic & renal impairment. Undesirable effects: Common: Gastrointestinal effects (nausea, vomiting, dyspepsia, diarrohea, constipation) sweating,

tremor, taste disturbance, sexual dysfunction, dry mouth, cough, postural hypotension, tachycardia, somnolence, visual disturbances, pruritis, hyponatraemia, possible changes in blood sugar

Interactions:

Metabolised by CYP2D6 enzymes.

May have increased concentrations with 2D6 inhibitors e.g. haloperidol, paroxetine and valproate sodium.

Inhibits CYP3A4, 2D6 and 2C so may have increased concentrations of drugs metabolised by CYP enzymes e.g. amitriptyline, codeine (decreased morphine concentrations, haloperidol, mexiletine, nortriptyline, ondansetron, paroxetine, tramadol, carbamazepine, clonazepam, dexamethasone, fentanyl, ketoconazole, methadone, methylphenidate, miconazole, midazolam, NSAIDs, omeprazole, phenobarbitone, prednisone, risperidone, phenytoin and warfarin.

Risk of serotonin syndrome with other proserotonergic drugs e.g. tricyclic antidepressants, carbamazepine, lithium

Dosing: Oral: 20-60mg in the morning S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Blocks the reuptake of serotonin, a neurotransmitter, in the CNS Onset: Depression, anxiety 1-2 weeks Pain, 3-7 days Peak response: 5-6 weeks Availability: Cap 20mg - fully funded Disp Tab 20mg - fully funded only if patient can’t swallow tablets and prescription is endorsed accordingly or for doses of 10mg, or when combined with capsules to facilitate incremental 10mg doses. Hepatic impairment: reduce dose or avoid Renal impairment: mild to moderate impairment, reduce dose (give on alternate days) Notes:

Fluoxetine has a half life of 48 hours but its active metabolite (norfluoxetine) has a half life of 11 days. Long half-life so withdrawal symptoms unlikely.

Watch for serotonin syndrome if switching antidepressants as it takes four to five half lives to clear a drug from the body i.e. 44 to 55 days for fluoxetine/norfluoxetine. Wait >5 weeks before starting an MAOI if stopping fluoxetine.

Do not start fluoxetine until 2 weeks after stopping an MAOI.

Tablets are dispersible in water allowing dosing increments of < 20mg. Capsule contents are also dispersible in water.

32

Drug Information

GABAPENTIN (Nupentin™, Arrow-Gabapentin™)

**Relevant Specialist** Class: anti-epileptic Indication: adjunctive treatment of seizures; neuropathic pain Unregistered Indications: hot flushes, anxiety Contraindications/cautions: Caution in renal impairment – reduce dose; psychotic illness (may precipitate episodes) Undesirable effects: Very Common: Drowsiness, dizziness Common: Amnesia, anxiety, fatigue, amblyopia, diplopia, nystagmus, ataxia, tremor, arthralgia,

myalgia, peripheral oedema, weight gain, dry mouth, pharyngitis, dyspepsia, diarrhoea Interactions:

Antacids containing aluminium or magnesium decrease bioavailability of gabapentin – dose 2 hours apart

Phenytoin serum concentrations may be increased by gabapentin

Note: valproate, carbamazepine & phenobarbitone serum concentrations not affected by gabapentin Dosing: Neuropathic Pain, adults: Commence on 300mg/day orally and increase by 300mg/day for 3-days then 300mg every 3-days as needed up to 1200mg tds. Usually given in 3 divided doses. Dose can be increased more slowly. Hot flushes: start slowly; increase up to 300mg tds if necessary Syringe Driver: N/A Mechanism of Action: chemical analogue of GABA; reduces calcium influx & release of neurotransmitters such as glutamine, substance P and noradrenaline. Onset of action: 1 to 3 hours Time to peak plasma conc: 2 to 3 hours Plasma half-life: half-life 5-7 hours; dose tds Duration of action: probably 8-12 hours; much longer in severe renal imp. Availability: Capsules 100mg, 300mg, 400mg; Tablet 600mg – funded under Special Authority Dose adjustment in renal impairment: 56% to 80% eliminated renally; reduce dose and extend dosing interval in renal impairment. Half-life increases to 2-days+ in moderate to severe imp. Notes:

Funded under Special Authority for the treatment of neuropathic pain. Initial application by any relevant practitioner– approvals valid 3 months where patient has tried and failed or not tolerated treatment with a tricyclic antidepressant Renewals valid for 2 years where patient has demonstrated a marked improvement in their control of pain.

33

Drug Information

GLYCERINE & THYMOL MOUTHWASH™

Class: Simple mouthwash Indication: Local pain relief for discomfort and swelling / refreshing mouthwash Unregistered Indications: Contraindications/cautions: Undesirable effects: Interactions: Dosing: diluted with warm water and used at frequent intervals Syringe Driver: Mechanism of Action: Peak Effect: Duration: Availability: mouthwash, 500ml - fully funded Dose adjustment in renal impairment: Dose adjustment in hepatic impairment:

34

Drug Information

GLYCOPYRROLATE (Glycopyrronium bromide™)

**Specialist/Hospice**

Class: anticholinergic - antisecretory/antispasmodic Indication: Drying secretions (premedication & control of upper airway secretions) Unregistered indications: "Death rattle" (retained secretions), drooling, inoperable intestinal obstruction, paraneoplastic pyrexia & sweating, smooth muscle spasm, subcutaneous injection/infusion Contraindications/cautions: Urinary retention, cardiac disease, glaucoma Undesirable effects: Very Common: Dry mouth, tachycardia Common: Urinary retention, visual problems, dizziness, constipation, drowsiness Interactions:

Anticholinergic so additive effects with other drugs which have anticholinergic effects e.g. cyclizine, amitriptyline, haloperidol, phenothiazines

May counteract prokinetic effects of metoclopramide/ domperidone Dosing: Oral: Not available S/C: 200 - 600 micrograms/24 hours Rectal: Not available Syringe driver: see compatibility chart Mechanism of action: Blocks cholinergic receptors Initial response (s/c): 30-40 minutes Duration of Action: 7 hours Availability: Inj 0.2mg/ml lml - not funded; Section 29 Notes:

Scopoderm TTS usually used first line.

Glycopyrrolate second line or may be an alternative to hyoscine when hyoscine has induced confusion in the elderly.

Consult hospice specialist for prescribing advice please.

35

Drug Information

HALOPERIDOL (Serenace™) Class: antipsychotic –butyrophenone; D2-receptor antagonist Indication: psychotic symptoms Unregistered indications: nausea, vomiting, agitated delirium, intractable hiccup, subcutaneous injection/infusion Contraindications/ cautions: Hepatic encephalopathy, epilepsy, Parkinson's Disease Undesirable effects: Common: Extrapyramidal symptoms (usually at 5-20mg/24 hours) e.g. oculogyric crisis, dystonia,

tremor, abnormal movements, restlessness, sedation, hypotension Interactions:

CYP enzymes - metabolised by CYP3A4 and 2D6.

May have increased concentrations with CYP inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, paroxetine and valproate sodium.

May have decreased concentrations with 3Α4 inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin and prednisone.

Inhibits CYP2D6 so may increase concentrations of drugs metabolised by 2D6 e.g. amitriptyline, codeine (decreases morphine concentrations), fluoxetine, methylphenidate, mexiletine, nortriptyline, ondansetron, paroxetine, risperidone and tramadol

Additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and opioids.

Lithium may enhance extrapyramidal symptoms.

Anticholinergic so additive effects with other drugs which have anticholinergic effects e.g. cyclizine, amitriptyline, phenothiazines

Dosing: Oral: parenteral = 3 : 2 Nausea/vomiting Delirium (see notes) oral: 1.5-3 mg once a day oral: 1.5-20mg per 24 hours S/C: 1-2mg/24 hours S/C: 1-15mg/24 hours

Syringe driver: see syringe driver compatibility table Mechanism of action: Nausea/vomiting - blocks dopamine receptors in the chemo-receptor trigger zone thus blocking input into the vomiting centre. Onset of action: 10-15 minutes s/c; > 1 hour (po) Duration of action: Up to 24 hours Plasma half-life: 13-35 hours Availability: Tab 0.5mg, 1.5mg, 5mg - fully funded Oral liq 2mg/ml - fully funded Inj 5mg/ml, 1ml - fully funded

Notes:

Useful as an antiemetic where causes of nausea and vomiting are biochemical imbalance or toxins.

Particularly useful in opioid induced nausea and vomiting (given as a single oral dose at night)

Once daily dose for nausea and vomiting usually given at night.

36

Drug Information

HYDROGEN PEROXIDE MOUTHWASH 6% (20 VOL)

Class: Mouthwash Indication: oral hygiene; cleansing Unregistered Indications: Contraindications/cautions: Undesirable effects: Interactions: Dosing: Dilute 15ml with half a glass of warm water and rinse the mouth for 2 - 3 minutes, 2 to 3 times a day Syringe Driver: N/A Mechanism of Action: Peak Effect: Duration: Availability: Solution, 20 vol - fully funded – maximum of 500ml per prescription Dose adjustment in renal impairment: Dose adjustment in hepatic impairment: Notes:

37

Drug Information

HYOSCINE HYDROBROMIDE (Scopoderm™, Hyoscine™) Class: antimuscarinic anticholinergic - antisecretory Indication: antisecretory premedication, prevention of motion sickness (TD route) Unregistered indications: sialorrhoea, drooling, death rattle, inoperable intestinal obstruction, paraneoplastic pyrexia and sweating, smooth muscle spasm Contraindications/cautions: Narrow-angle glaucoma; caution in elderly, urinary retention, cardiac disease Undesirable effects: Very Common: Dry mouth Common: Tachycardia, hypotension (especially with morphine),urinary retention, visual problems,

dizziness, constipation, drowsiness, hallucinations (more common in the elderly) Interactions:

Anticholinergic so additive effects with other drugs which have anticholinergic effects e.g. cyclizine, amitriptyline, haloperidol, phenothiazines

May counteract prokinetic effects of metoclopramide/ domperidone Dosing: Oral: Not available S/C: 0.4-2.4mg/24 hours (usually 0.4-0.8mg stat) Rectal: Not available Patch: 1 patch / 72 hours (behind the ear) Syringe driver: see syringe driver compatibility table Mechanism of action: Blocks cholinergic receptors in CNS and the GIT Time to Peak effect: 20-60 minutes (s/c); TD 24 hours. Patch anecdotally has some effect after 1-2 hours Duration: Patch – up to 72 hours plus depot effect Plasma half-life: 5-6 hours Availability: Inj 0.4mg/ml fully funded Hyoscine

TM (Hospira, Martindale)

Patch l.5mg partially funded with Special Authority (ScopodermTM

)

Special Authority criteria - for control of intractable nausea, vomiting or inability to swallow saliva in the treatment of malignancy or chronic disease where patient cannot tolerate or does not adequately respond to oral anti-nausea agents; underlying malignancy or chronic disease must be specified. Approvals valid for 1 year; applications by any medical practitioner.

Notes:

Thought to cross the blood brain barrier more easily than hyoscine butylbromide.

Risk of confusion in the elderly is high.

38

Drug Information

HYOSCINE BUTYLBROMIDE (Buscopan™, Gastro-soothe™) Class: antispasmodic - gastrointestinal tract Indication: GI spasm/colic Unregistered indications: Some action as anti-emetic and antisecretory. Contraindications/cautions: Megacolon, stenosis, glaucoma, tachycardia, urinary retention. Avoid in porphyria. Undesirable effects: Very Common: Dry mouth Common: Urinary retention, tachycardia, visual problems, dizziness, constipation Interactions:

Anticholinergic so additive effects with other drugs which have anticholinergic effects e.g. cyclizine, amitriptyline, haloperidol, phenothiazines

May counteract prokinetic effects of metoclopramide/ domperidone Dosing: Oral: 20mg four times a day S/C: 40-100mg/24 hours Rectal: Not available Syringe driver: see syringe driver compatibility table Mechanism of action: Blocks the effect of acetylcholine on gastrointestinal smooth muscle causing relaxation. Onset: Oral: 1-2 hours S/C: 5-10 minutes Duration: Oral: 2 hours or less Availability: Tab 10mg - fully funded (Gastro-soothe™) Inj 20mg/ml, 1ml - fully funded (Buscopan™) Notes:

May be useful with steroids in intestinal obstruction.

Doesn't cross the blood-brain barrier so doesn't cause drowsiness or have a central antiemetic action.

Only 8-10% absorbed orally.

39

Drug Information

IBUPROFEN (Brufen™, Fenpaed™, Arrowcare™) Class: non-steroidal anti-inflammatory drug (NSAID); non-selective COX inhibitor Indication: pain associated with inflammation, antipyretic Unregistered indications: Contraindications/cautions: GI ulceration, asthma (in sensitive patients), renal, cardiac or hepatic impairment. Undesirable effects: Common: GI ulceration (more common if elderly, on steroids or aspirin), diarrhoea, indigestion,

nausea, dizziness, rash, nephrotoxicity, hepatitis, oedema, hypertension, headache, tinnitus * Inhibits platelet aggregation- may prolong bleeding time. Interactions:

CYP enzymes - metabolised by CYP2C9.

May have increased concentrations with 2C9 inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, miconazole and valproate sodium.

May have decreased concentrations with 2C9 inducers e.g. dexamethasone, phenobarbitone and phenytoin

ACE inhibitors (e.g. enalapril) increase risk of renal toxicity and hyperkalaemia

Increased risk of gastro-intestinal bleed with corticosteroids

Concentrations of lithium, digoxin, methotrexate and warfarin may be raised - monitor.

May reduce effects of diuretics (e.g. frusemide) and antihypertensives Dosing: Oral: Normal release: 600-2400mg per day in 3 to 4 divided doses SR : 1600mg once a day - 2400mg in 2 divided doses S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Inhibits prostaglandin synthesis. Prostaglandins are involved in inflammation and pain. Peak effect: 0.5-1.5 hours Availability: Tab 200mg - fully funded (Arrowcare™) Tab 400mg, 600mg - partially funded (Brufen

TM)

Tab sustained release 800mg - fully funded (Brufen™) Oral liquid - fully funded (Fenpaed

TM)

Partially funded preparations may be fully subsidised under Special Authority – criteria include inflammatory arthritis and well controlled. Notes:

Co-analgesic often used with opioids in the treatment of bone and soft tissue pain.

Patients at risk of gastro-intestinal bleeds should be prescribed gastric protection (e.g. omeprazole) prophylactically.

40

Drug Information

ΚΕΤΑΜΙΝΕ (Ketalar™) **Specialist/Hospice**

Class: anaesthetic Indication: general anaesthesia Unregistered indications: Severe pain unresponsive to standard therapies (sub-anaesthetic doses); subcutaneous injection/infusion Contraindications/cautions: Hypertension, severe cardiovascular disease, recent MI, history of stroke, tendency to hallucinations, alcohol abuse, epilepsy Undesirable effects: Very Common: Hallucinations (see notes below), delirium, tachycardia, hypertension Common: Hypotension, bradycardia, laryngospasm, diplopia, respiratory depression, nausea Interactions: Additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and opioids. Use with caution in those on antihypertensives – monitor bp. Caution with patients on thyroxine – increased risk of hypertension & tachycardia. Dosing: Oral: Not available (injection has been given orally) S/C: 60 - 240mg in 24 hours (initially 0.1-0.5mg/kg/hr) Rectal: Not available Syringe driver: diluent is normal saline; see compatibility chart Mechanism of action: NMDA-receptor-channel-blocker; also interacts with other calcium & sodium channels, dopamine receptors, cholinergic transmission, noradrenergic and serotoninergic reuptake inhibition, opioid effects and an anti=inflammatory effect. Onset of action: 15-30 minutes (s/c) Duration (oral): 4-6 hours. Generally given by continuous subcut infusion Availability: Inj 200mg/2ml (2ml) - not funded Notes:

May be useful in opioid tolerance/intolerance, in "wind-up" and may allow a reduction in opioid dose.

May be useful in neuropathic pain.

If hallucinations occur reduce the dose of ketamine and give a benzodiazepine (e.g. diazepam 5mg orally, midazolam 5mg sc) or haloperidol 2-5mg orally or sc.

Hospice specialist team to prescribe and monitor.

41

Drug Information

KETOCONAZOLE (Nizoral™) Class: antifungal - imidazole Indication: fungal infections Unregistered indications: Contraindications/ cautions: hepatic impairment Undesirable effects: Common: Nausea, vomiting, abdominal pain, headache, rash, pruritus, raised liver enzymes/hepatitis/liver damage (usually if given for more than 14 days), blood disorders, dizziness, hypertension Interactions:

CYP enzymes - metabolised by CYP3A4.

May have increased concentrations with 3Α4 inhibitors e.g. fluconazole, fluoxetine, metronidazole and valproate sodium.

May have decreased concentrations with 3Α4 inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin and prednisone.

May increase concentrations of amitriptyline, clonazepam, dexamethasone, fentanyl, methadone, miconazole, midazolam, omeprazole, prednisone, risperidone, tramadol, warfarin, carbamazepine, diclofenac, ibuprofen, naproxen, phenobarbitone, phenytoin and tenoxicam.

Disulfiram-like reaction with alcohol Absorption decreased by antacids, ranitidine, omeprazole. Dosing: Oral: 200mg once a day for 5 to 7 days S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Increases fungal cell membrane permeability Availability: Tab 200mg - fully funded – specialist recommendation required. Notes:

More hepatotoxic than fluconazole. LFTs recommended if treatment >14days

Avoid alcohol.

42

Drug Information

LAX SACHETS™ (Macrogol 3350, sodium chloride, sodium bicarbonate, potassium chloride, potassium acesulfame) Class: laxative, osmotic Indication: constipation including faecal impaction Unregistered Indications: Contraindications/cautions: Intestinal obstruction or perforation, ileus and severe inflammatory conditions, cardiac disease (contains sodium and potassium) Adverse reactions: Less common: abdominal distension and pain, nausea Metabolism/Clearance: Not absorbed Interactions: Few as not absorbed – may affect the absorption of some drugs Dosing: Constipation: 1 to 3 sachets per day Faecal impaction: 8 sachets/ day taken within 6 hours for a maximum of 3 days. (if cardiovascular problems, do not take more than 2 sachets over any 1 hour Each sachet should be dissolved in 125ml water. For faecal impaction dissolve 8 sachets in 1 litre of water - store the liquid in the fridge and discard any unused liquid after 6 hours Syringe Driver: not available Mechanism of Action: Osmotic action in the gut to increase liquid content of stools but with no net loss of sodium, potassium or water Peak Effect: Duration: Availability: Sachets (30 per box) Partially funded, Special Authority available – Problematic constipation where rectal preparation is needed after adequate trial with other oral laxatives Dose adjustment in renal impairment: no adjustment necessary Dose adjustment in hepatic impairment: no adjustment necessary Notes:

Effective laxative in palliative care

More acceptable than lactulose

43

Drug Information

LEVOMEPROMAZINE (Nozinan™) Class: phenothiazine antipsychotic, anti-emetic Indication: psychosis, terminal agitation with or without delerium, intractable pain (with strong opioids) Unregistered indications: nausea and vomiting Contraindications/cautions: Parkinsonism, postural hypotension, epilepsy (lowers seizure threshold in higher doses), hypothyroidism Undesirable effects: Very Common: Drowsiness, sedation, postural hypotension Common: Dry mouth, hypotension, extrapyramidal side-effects (long term high dose usually) Interactions:

Additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), other phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and opioids.

May prolong cardiac QT interval so caution with other drugs that prolong the QT interval e.g. amitriptyline

Dosing: Nausea/vomiting: Oral: Second or thirdline anti-emetic: 6.25-12.5mg daily for nausea/vomiting - usually given once

daily at night, start with 6.25mg) S/c: 5mg over 24 hours Rectal: N/A Pain, restlessness, distress, delirium (start with low dose & titrate) Oral: 6.25-50mg every 4 to 8 hours S/c: 5-200mg/24 hours (doses < 25mg associated with less sedation) Rectal: Not available Syringe driver: See syringe driver compatibility table Mechanism of action: As an anti-emetic, acts on multiple receptors (D2, H1, alpha-adrenergic & muscarinic) Onset: (s/c, po): 30 minutes Duration: 12-24 hours Half life: 15-30 hours Availability: Tab 25mg, 100mg - fully funded Inj 25mg/ml lml - fully funded Notes:

Only phenothiazine with analgesic properties.

Most useful in treating nausea & vomiting due to its action on several receptors and once daily dosing (nocte)

Benztropine 2mg may be useful in alleviating extrapyramidal side-effects.

6.25mg oral dose is given as quarter of a 25mg tablet

5 mg subcut is 0.2ml of the 25mg/ml injection.

Metabolised in kidneys – care in renal dysfunction

44

Drug Information

LOPERAMIDE (Diamide Relief™, Nodia™)

Class: antidiarrhoeal – peripheral opioid receptior agonist Indication: acute & chronic diarrhoea Unregistered indications: ileostomy (to improve faecal consistency) Contraindications/cautions: diarrhoea due to infection or antibiotics; caution in patients on clozapine (additive inhibition of intestinal motility) Undesirable effects: Common: Flatulence, abdominal pain, bloating; giddiness Interactions:

May be antagonised by prokinetics e.g. metoclopramide/ domperidone

CNS adverse effects may occur with P-glycoprotein inhibitors eg grapefruit juice, ketoconazole, itraconazole, tamoxifen

Dosing: Oral: 2mg after each loose stool to a max. of 16mg/24 hours S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Binds to opioid receptors in GIT (potent μ-opioid receptor agonist). May also affect cholinergic receptors Onset: 1 - 3 hours; maximum effect 16-24 hours Duration of action: up to 3 days Availability: Tab 2mg - fully funded (Nodia™) Notes:

May not be of benefit if patient is already taking morphine.

Up to 50% excreted unchanged in the faeces following oral administration.

45

Drug Information

LORAZEPAM (Ativan™) Class: anxiolytic - benzodiazepine Indication: short-term treatment of anxiety or insomnia, status epilepticus, nausea & vomiting (chemo-related), peri-operative sedation, acute agitation or mania. Unregistered indications: Terminal agitation, alcohol withdrawal, serotonin toxicity Contraindications/cautions: Respiratory depression, sleep apnoea syndrome, myasthenia gravis Undesirable effects: Common: Sedation, fatigue, impaired co-ordination, disorientation, depression, disinhibition, amnesia Uncommon: Respiratory depression (high dose) Interactions:

Additive CNS effects with other CNS depressants e.g. other benzodiazepines (e.g.midazolam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and opioids.

Dosing: Oral: 1-2mg in 2 to 3 divided doses (max 10mg/24 hours) S/C: Injection not available Rectal: Not available Syringe driver: Not available Mechanism of action: May enhance the effect of GABA -an inhibitory neurotransmitter in the CNS Onset: Oral 10-15 minutes Duration: Oral 6-72 hours Half life: 10-20 hours Availability: Tab 1 mg, 2.5mg - fully funded, month restriction, prescription only Notes:

Not metabolised by CYP450 enzymes so less likely to interact with other drugs compared with other benzodiazepines.

Theoretically most appropriate benzodiazepine to use in hepatic failure.

Approximate equivalent oral anxiolytic-sedative doses: See clonazepam page

Pharmacological properties of benzodiazepines and other hypnotics: See clonazepam page.

No longer available in a sublingual tablet 0.5mg.

46

Drug Information

METHADONE (Biodone™, Methatabs™, Methadone inj BP (AFT)) **Specialist/Hospice** Note: Methadone for cancer pain, including dose titrations, must be prescribed under specialist supervision due to individual variability in half-life and response (extensive tissue distribution and variable clearance). Class: analgesic – opioid Indications: Moderate to severe pain, symptomatic relief of cough, opioid addiction. Unregistered use: Methadone can be used in place of other strong opioids such as morphine & fentanyl, in the management of cancer pain where either tolerance has developed to the analgesic effect of the existing opioid, or patient has experienced intolerable adverse effects caused by the existing opioid (eg nausea, vomiting, hallucinations, cognitive impairment, drowsiness). May be useful in management of neuropathic or bone pain due to action on NMDA receptors (based on clinical experience). Pain relief in renal failure & pain poorly-responsive to morphine Contraindications/cautions: Conversion to methadone is contraindicated in moribund patients since initial titration requires patient participation. Dose conversion and titration must be supervised by a palliative care specialist physician due to complexities of conversion and huge individual variation in response. Methadone may accumulate and progressive side-effects may occur despite a consistent dose – this is due to long & unpredictable half-life. Half-life can vary from 8 to 80 hours (individual variation). Drug interactions and prolongation of the QT interval prompted the FDA to issue a safety warning about methadone.

Undesirable effects:

Typical of opioid drugs (constipation, nausea, sedation, cognitive impairment & possibly hallucination). May be less drowsiness, nausea and constipation at appropriate dosages (compared to morphine).

Has a long and variable half-life so watch for signs of toxicity e.g. decrease in respiratory rate and/or mental status (particularly in the elderly).

Patients may experience morphine withdrawal symptoms when changing from morphine to methadone (fatigue, anxiety, restlessness, irritability, insomnia, yawning, salivation, sweating, nausea, vomiting, anorexia, abdominal pain, diarrhoea). These symptoms will be managed under specialist care, usually as an inpatient.

Interactions:

CYP enzymes - metabolised by CYP3A4.

May have increased methadone concentrations with 3A4 inhibitors e.g. fluconazole, ketoconazole, metronidazole, fluoxetine, macrolide antibiotics, cimetidine and valproate sodium (due to these drugs decreasing methadone metabolism).

47

Drug Information

Additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and other opioids.

Additive respiratory depression with benzodiazepines and other respiratory depressants

May have decreased methadone concentrations with 3A4 inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin, and prednisone (due to these drugs increasing methadone metabolism).

Dosing: (as prescribed by hospice specialist) Oral: 5-10mg 4-6 hourly initially then twice daily S/C: 75-100% of oral dose (conversion under supervision of hospice Dr please) Rectal: Not available in NZ

Syringe driver: See compatibility chart. Subcutaneous injection may be irritant – minimise by dilution in 30ml syringe. Diluent used is water for injection.

Mechanism of action: Stimulates opioid receptors in the CNS and GIT and also acts at NMDA receptors.

Onset: 0.5 - 1 hour initially Duration: 6-8 hours initially then 22-48 hours on repeat dosing. Half-life: 8-80 hours

Availability: Tab 5mg - fully funded Liquid 2mg/ml, 5mg/ml, 10mg/ml - fully funded Inj 10mg/ml, 1ml - fully funded

Controlled drug form required.

Notes:

An understanding of the pharmacology of methadone is important for prescribers.

Renal and hepatic impairment are rarely a problem; monitor.

Prescribe methadone liquid or tablets for breakthrough pain. Funded brand of tablets are no longer scored so patients may have difficulty halving to give a 2.5mg dose. (Note: be aware of the potential for accumulation of methadone)

May be useful in opioid rotation.

Conversion from morphine is variable as individuals have differing methadone half lives. Consult hospice specialist team if considering using methadone.

Slow dose titration and close monitoring of the patient are recommended when changing the dose of methadone.

As affects NMDA receptors may prevent "wind up" on long term use and is useful in neuropathic pain.

Subcutaneous injection may be irritant – use 30ml syringe & dilute to 48mm.

48

Drug Information

METHYLPHENIDATE (Ritalin™, Ritalin SR™, Rubifen™, Rubifen SR™)

**Specialist/Hospice** Class: central stimulant - amphetamine related Indication: attention deficit hyperactivity disorder. Unregistered indications: Depression, opioid-related drowsiness, narcolepsy Contraindications/cautions: Anxiety, agitation,glaucoma, hyperthyroidism, cardiac problems, hypertension, epilepsy, pre-existing prescription of anti-psychotic drug Undesirable effects: Very Common: Nervousness, insomnia Common: Tachycardia, dizziness, headache, palpitations, nausea, vomiting, dry mouth,abdominal pain Interactions:

CYP enzymes - may be metabolised by CYP2D6.

May have increased concentrations with 2D6 inhibitors e.g. fluoxetine, haloperidol, paroxetine and valproate sodium.

May enhance analgesic effect of some opioids, decrease sedation

With MAOIs may cause hypertensive crisis

May antagonise hypotensive effect of adrenergic blockers - hypertension with tricyclic antidepressants may occur

May antagonize the anti-epileptic effect of phenytoin

Inhibits metabolism of warfarin Dosing: Depression (max. adult dose of lmg/kg/24 hours) Oral: starting dose 2.5-5mg bd (morning and mid-day); if necessary increasing tby daily increments

of 2.5mg bd to 20mg bd S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Acts as a stimulant in the CNS Onset: 20-40 minutes Availability:

Tab 5mg, 10mg, 10mg SR, 20mg SR

fully funded only for narcolepsy or ADHD, with Special Authority.

*Prescribed only by medical practitioners with a vocational scope in paediatrics, psychiatry, palliative care or by other medical practitionersafter consultation with relevant specialist

Not funded for unregistered indications above.

Controlled drug form required. Notes

Not funded for palliative care.

Doses given morning and midday.

Patients may respond to short courses of 2-3 weeks then withdraw. *Ref: Medicines Act 1981, and regulation 22 of the Misuse of Drugs Regulations 1977

49

Drug Information

METOCLOPRAMIDE (Metamide™, Metoclopramide PfizerTM) Class: antiemetic - prokinetic Indication: nausea and/or vomiting, dysmotility dyspepsia, flatulence, heartburn, migraine Unregistered use: hiccups, subcutaneous injection/infusion Contraindications/cautions: Phaeochromocytoma, complete intestinal obstruction. Young persons are more prone to extrapyramidal side-effects. Caution in hepatic & renal impairment. Undesirable effects: Common: Tardive dyskinesia - usually on prolonged use, extrapyramidal effects e.g. parkinsonism,

akathisia (usually at doses > 30mg/24 hours-switch to domperidone which doesn't cross the blood-brain barrier),

Uncommon: Diarrhoea, restlessness, dowsiness. Interactions:

Morphine - theoretical faster onset of action of SR morphine if given with metoclopramide

Opioids may counteract prokinetic activity of metoclopramide

Lithium - increased risk of extrapyramidal effects and neurotoxicity

Effect may be counteracted by anticholinergics e.g. hyoscine Dosing: Oral: 10mg tds to qid S/C: 30-60mg over 24 hours (watch for extrapyramidal effects at > 30mg/24 hours) and 10mg

po/sc prn. Doses of up 10 1oomg/24 hours used to treat delayed gastric emptying Rectal: 10mg up to three times a day Syringe driver: see syringe driver compatibility table. Mechanism of action: Blocks dopamine receptors in the gastrointestinal tract (increasing peristalsis), CNS and chemoreceptortrigger zone (CTZ) Onset of action: 15-60 minutes (po) Plasma half-life: 2.5-5 hours Duration of action: 1-2 hours (single dose) Availability:

Tabs 10mg - Fully funded (MetamideTM

) Inj 10mg/2ml - Fully funded Hepatic impairment: Reduce dose Renal impairment: Reduce dose; increased risk of extrapyramidal effects. Notes:

“High dose metoclopramide” may work via 5HT3 antagonism (like ondansetron) but is associated with severe extrapyramidal effects.

Most effective for nausea/vomiting due to gastric stasis.

Suppositories not funded – check availability with pharmacy.

50

Drug Information

METRONIDAZOLE (Flagyl™, Trichozole™, Rozex™) Class: antibiotic - anti-anaerobic & protazoal infections Indication: anaerobic or protazoal infections, helicon pylori gastritis. Unregistered indications: malodour caused by anaerobic infection; pseudomembranous colitis. Contraindications/cautions: Undesirable effects: Very Common: GI upset, urticaria, unpleasant taste, furry tongue Common: Drowsiness, headache, dizziness, urine darkening Interactions:

CYP enzymes - inhibits CYP2C9 and 3A4

May have increased concentrations of carbamazepine, NSAIDs, phenytoin, warfarin, amitriptyline, clonazepam, dexamethasone, fentanyl, ketoconazole, methadone, miconazole, midazolam, omeprazole, phenobarbitone, phenytoin, prednisone, risperidone, tramadol and warfarin.

Disulfiram-like reaction with alcohol – take care when prescribing other medications that they are alcohol-free.

May increase toxicity of lithium Dosing: Oral: 400mg three times a day for 2-weeks (anaerobic infections) or 400mg bd in elderly

debilitiated patients Rectal: 1g three times a day for 3 days then twice a day Topical: Apply twice a day; tablets crushed & podwer applied, or tablets crushed and mixed into

lubricating gel which is then applied. Dose from crushed tablets is several times greater than from commercial preparations. Higher dose may have observable impact (reduced odour) within 24-hours compared with several days with commercial preparations.

Syringe driver: not applicable Mechanism of action: In malodorous wounds kills anaerobes responsible for the smell. Availability: Tabs 200mg, 400mg - fully funded (Trichozole

TM)

Oral liq 200mg/ 5ml - partially funded (Flagyl-STM

) Supp 500mg, 1g - fully funded (Flagyl

TM)

Inj 500mg - not funded Topical Gel 0.5% - not funded Notes:

200mg tablets crushed to a fine powder have been used topically in treatment of malodorous wounds. 200mg tablets (non-film coated white tablets) are cosmetically preferable to the 400mg tablets, which are yellow in colour.

Take care not to inhale powder.

51

Drug Information

MICONAZOLE (Decozol™, Micreme™, Micreme-H™) Class: antifungal - imidazole Indication: fungal infection - topical, oral, GI, vaginal Unregistered indications: Contraindications/cautions: Hepatic impairment; concomitant terfenadine, cisapride, astemizole, quinidine, pimozide, oral midazolam and triazolam, CYP3A4 metabolised HMG-CoA reductase inhibitors, e.g. simvastatin, lovatstatin. Undesirable effects: Common: oral gel - GI upset; topical/vaginal- burning, itching Interactions: NB: Applies to oral gel/vaginal preparations also (absorption is likely)

CYP enzymes - metabolised by CYP3A4.

May have increased concentrations with 3A4 inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole and valproate sodium.

May have decreased concentrations with 3A4 inducers e.g. carbamazepine, dexamethasone, phenytoin and prednisone.

Inhibits CYP3A4 and 2C9 so may increase concentrations of drugs metabolised by them e.g. amitriptyline, carbamazepine, clonazepam, dexamethasone, fentanyl, ketoconazole, methadone, midazolam, omeprazole, prednisone, risperidone, tramadol, NSAIDs, phenobarbitone, phenytoin and warfarin.

May antagonise effect of amphotericin Dosing: Oral: 50mg four times a day for 7 days S/C: Not available Rectal: Not available Topical: Apply twice a day Vaginal: Use at night Syringe driver: Not available Mechanism of action: Increases fungal cell membrane permeability Availability: Oral gel 2% 40g - fully funded (Decozol

TM)

Topical cream 2% - some fully funded Topical lotion 2% - partially funded Powder 2% 20g - not funded Spray 2% 100g - not funded Tincture 2% 30ml - partially funded Vaginal cream 2% - not fully funded Notes:

Interactions listed above may arise with oral gel and vaginal preparation due to absorption of micronazole.

Caution using miconazole oral gel in patients on warfarin (increases warfarin concentration).

52

Drug Information

MICOLETTE TM Enema (Sodium citrate 450mg, sodium laurylsulphoacetate 45mg, sorbitol 3.125g, sorbic acid 5mg, water to 5ml)

Class: rectal laxative - stimulant, faecal softener and osmotic Indication: constipation, bowel evacuation Unregistered indications: Contraindications/ cautions: Undesirable effects: rectal burning sensation Interactions: Dosing: Oral: not available S/C: not available Rectal: 1 tube as required Syringe driver: not available Mechanism of action: May stimulate colonic activity via nerves in the intestinal mucosa (sodium citrate) and increases fluid uptake by stools thus softening them (sodium laurylsulphate, sorbitol). Onset: Works in about 15 minutes Availability: Enema 5ml fully funded, only on prescription

53

Drug Information

MIDAZOLAM (HypnovelTM)

Class: sedative- benzodiazepine Indication: Anaesthetic induction agent, sedative for minor procedures, Unregistered indications: Subcutaneous injection/infusion (used for terminal agitation in palliative care), intractable hiccup, epilepsy, status epilepticus, myoclonus, nasal spray (anxiety-related dyspnoea); terminal breathlessness Contraindications/cautions: Unless for end of life care: acute or severe pulmonary insufficiency, sleep apnoea, severe liver disease, myasthenia gravis. Undesirable effects: Common: Fatigue, drowsiness, amnesia Interactions:

CYP enzymes - metabolised by CYP3A4.

May have increased concentrations with 3A4 inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole and valproate sodium.

May have decreased concentrations with 3A4 inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin and prednisone.

Additive CNS effects with other CNS depressants e.g. other benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and opioids.

Avoid grapefruit juice – may have increased concentrations of midazolam due to inhibition of metabolism.

Dosing: Oral: 7.5-15mg at bed-time S/C: 5-10mg s/c or 5-60mg/24 hours (up to 150mg in terminal sedation) I/N: 1 – 2 mg (1-2 puffs in each nostril) up to hourly Rectal: Not available Syringe driver: see syringe driver compatibility table Mechanism of action: May enhance the effect of GABA - an inhibitory neurotransmitter in CNS Peak concentrations: Oral 20-50 min, sc 5-10 min, iv 2-3 mins Duration: 15 minutes to several hours. Half life: 2-5 hours Availability: Tab 7.5mg - partially funded, one month only on Rx Inj 1mg/ml 5ml, 5mg/ml 3ml -fully funded Nasal Spray – made using 15mg/3ml injection solution – drug funded but spray device & manufacture costs not funded. (Made by community pharmacy) Notes:

Midazolam is a very short acting benzodiazepine so dose titration to response is easier than with longer acting benzodiazepines e.g. clonazepam.

Intra-nasal midazolam used for anxiety-related dyspnoea, 1-2mg up to hourly (1-2 puffs in each nostril)

Benzodiazepines may reduce dyspnoea by anxiolytic and sedative effects.

Half-life may be prolonged in the elderly

Approximate equivalent oral anxiolytic-sedative doses: See clonazepam page

Pharmacological properties of benzodiazepines and other hypnotics: See clonazepam page.

54

Drug Information

MIRTAZAPINE (Avanza™, Apo-MirtazapineTM)

Class: antidepressant – central presynaptic alpha 2 and 5HT antogonist Indication: major depression Unregistered indications: nausea Contraindications/cautions: bipolar depression, epilepsy, cardiac disease, prostatic hypertrophy, diabetes, abrupt withdrawal. Undesirable effects: Common: increased appetite, dizziness, headache, dry mouth Uncommon: convulsions, tremor, nightwares, mania, syncope, hyponatraemia, nausea Metablolism/clearance: metabolized by metabolizing enzyme CYP2D6, 1A2 and 3A4/5/7 mainly in the liver to at least one active metabolite (by CYP3A4/5/7) Interactions:

Increased clinical effect/toxicity of mirtazapine (due to increased blook concentrations of parent) may occur with some CYP metabolizing enzyme inhibitors (see above) e.g. bupropion, aprepitant, ciprofloxacin, clarithromycin, fluconazole, fluoxetine, grapefruit juice, itraconazole, ketoconazole, paroxetine, quinine, valproate

Decreased clinical effect/toxicity of mirtazapine (due to decreased blood concentrations of parent) may occur with some CYP metabolism enzyme inducers (see above) e.g. broccoli, carbamazepine, dexamethasone, phenobarbitone, phenytoin, prednisone, rifampicin, smoking, St John’s wort

Additive risk of serotonin symdrome(potentially fatal syndrome – symptoms include sweating, diarrhea, confusion) with other serotonergic drugs e.g. amitriptyline, carbamazepine, fluoxetine, paroxetine, tramadol, lithium

Dosing: Oral: 15-45mg at bedtime Sc: not available Syringe driver: not available Mechanism of Action: Blocks presynaptic alpha 2 and 5HT2 and 3 receptors increasing central nonadrenaline and serotonin (blocking 5HT2 and 5HT3 receptors allowing stimulation of 5HT1 receptors) Peak effect: Oral 2 hours Half Life: 20 to 40 hours Availability: Tab 30mg, 45 mg Full funded as below Special Authority available for severe major depression after a trial of two different antidepressants or in an inpatient who has trailled one antidepressant.

55

Drug Information

MORPHINE (m-Eslon™, Morphine Sulphate™, RA-Morph™, RMS™, Sevredol™, Arrow-Morphine LA™, Morphine Tartrate™)

Class: analgesic - opioid Indication: Opioid analgesic for severe pain. More effective in nociceptive than in neuropathic/visceral pains Unregistered indications: Dyspnoea, cough, diarrhea, moderate pain Contraindications/cautions: Morphine hypersensitivity/allergy (past nausea/hallucination with opioids aren't contraindications). Undesirable effects: Very Common: Nausea/vomiting (10-30%)- can give haloperidol (usually transient, for 1-5 days) or other

anti-emetic, constipation (90%) - give a stimulant & softener laxative prophylactically, dry mouth, dizziness, sedation (usually transient and on initiation or dose increase)

Common: Respiratory depression usually only at high doses-pain is an antidote- give naloxone if severe, visual problems-may see things upside down/flipping, myoclonic jerking-sign of toxicity - try a different opioid, delirium (2%)-give haloperidol

Uncommon: Hallucinations, hyperalgesia, raised intracranial pressure, biliary/urinary tract spasm, muscle rigidity, pruritus, pulmonary oedema, physical dependence (irrelevant in dying)

Interactions:

Additive CNS effect with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline) and other opioids.

Metoclopramide - theoretical faster onset of action of SR morphine Dosing: Pain: (initially use the normal release, titrate to pain, then convert to slow release) Oral: normal release initially 5-10mg 4 hourly Oral: slow release initially 10-30mg 12 hourly

rescue doses of normal release are usually 20% of total daily dose and should be prescribed as required. Normal release available in tablets or liquid.

although there is no real maximum dose usual doses are less than 200mg/ day. Doses of > 400mg/day should trigger consideration of co-analgesia

review doses regularly S/C: oral : sc = 2 : 1 Rectal: oral : rectal = 1 : 1 Breathlessness, cough Oral: normal release 5-10mg 4 hourly Syringe driver: see syringe driver compatibility table Mechanism of action: Stimulates p (and other) opioid receptors in the CNS and GIT. Peak effect: Oral normal release: 1 hour Duration: Oral normal release/sc: 4-5 hours Oral slow release: 8-12 hours

56

Drug Information Renal impairment: Reduce dose in renal impairment; use alternative opioid in renal failure Hepatic impairment: Bioavailability of morphine is increased but half-life is unchanged. Use lower than usual initial doses and titrate. Availability:

Cap, long acting, 10mg, 30mg, 60mg, 100mg, 200mg - fully funded

Tab, long acting, 10mg, 30mg, 60mg, 100mg – fully funded

Oral liq 1mg, 2mg, 5mg, 10mg /ml (RA MorphTM

) 200ml - fully funded

Tab normal release 10mg, 20mg (SevredolTM

) - fully funded

Inj 5mg/ml, 10mg/ml, 15mg/ml, 30mg/ml –sulphate -fully funded

Inj 80mg/ml 1.5ml, 80mg/ml 5ml as tartrate - fully funded

Suppositories 20mg, 30mg – may be difficult to source; some are fully funded, only on Section 29. Controlled drug form required.

Notes:

Tolerance to effect is rare and progressive disease is the most likely cause of dose fade.

Toxicity: Decrease in respiratory rate, mental status, blood pressure. Give naloxone (see naloxone page).

m-EslonTM

capsules can be opened and sprinkled on food or given via a PEG or nasogastric tube. Cannot be given rectally.

RA MorphTM

– prepackaged in 200ml bottles; please prescribe in 200ml lots Colour-coded labeling We recommend prescribing 1mg/ml and increasing to 10mg/ml (with very clear directions re dose)

when required. Avoid 2mg/ml and 5mg/ml – changes in strength can be confusing. Take care to prescribe an appropriate breakthrough dose (20% of total daily dose is

recommended).

57

Drug Information

NALOXONE (Baxter brand) **Specialist/Hospice** Class: opioid antagonist Indication: opioid overdose Unregistered indications: may enhance opioid analgesia and alleviate side-effects at very low dose Contraindications/cautions: cardiovascular disease Undesirable effects: Very Common: Nausea, vomiting, tachycardia, sweating, raised blood pressure (opioid withdrawal) Interactions: Blocks the action of opioids eg morphine, fentanyl, methadone, oxycodone Dosing: If respiratory rate < 8 per minute, patient unconscious or cyanosed and not in terminal phase: IV: seek advice; use low doses Oral: not available S/C: can start with 40mcg dose and repeat; or 100mcg. Seek guidance. Rectal: not available Syringe driver: not applicable Mechanism of action: Blocks action of opioids at opioid receptors Onset: sc/im 15 minutes Duration: 15-90 minutes Availability: Inj 0.4mg/ml, 1ml fully funded Baxter brand Inj 0.02mg/ml, 2ml fully funded Baxter brand Notes:

Can be given IM or sc; IV route used also.

Reversal of respiratory depression will result in reversal of analgesia and withdrawal symptoms if physiologically dependent.

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Drug Information

NAPROXEN (Naprosyn™, Noflam™) Class: non-steroidal anti-inflammatory drug (NSAID), non-selective COX inhibitor Indication: pain associated with inflammation Unregistered indications: cancer pain, neoplastic fever, Contraindications/cautions: GI ulceration, asthma (in sensitive patients), renal, cardiac or hepatic impairment. Undesirable effects: Very Common: Headache Common: GI ulceration (more common if elderly, on steroids or aspirin), nervousness, drowsiness,

tinnitus, oedema, haemolysis, diarrhoea, indigestion, nausea, constipation, rash Inhibits platelet aggregation - may prolong bleeding time – caution with warfarin.

Interactions:

CYP enzymes - metabolised by CYP2C9.

May have increased concentrations with 2C9 inhibitors e.g. fluoxetine, fluconazole, ketoconazole, metronidazole, miconazole and valproate sodium.

May have decreased concentrations with 2C9 inducers e.g. dexamethasone, phenobarbitone and phenytoin

Concentrations of lithium, digoxin, methotrexate and warfarin may be raised - monitor.

May reduce effects of diuretics (e.g. frusemide) and beta blockers

ACE inhibitors (e.g. enalapril) increase risk of renal toxicity and hyperkalaemia.

Additive risk of bleeding with warfarin and heparins. Dosing: Oral: Normal release 500-1000mg per day in two divided doses

Sustained release 750-1000mg per day as a single dose S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Inhibits prostaglandin synthesis (involved in pain and inflammation) Onset of action: 20-30 minutes Duration: 6-8 hours (single dose); >12 hours with multiple doses Availability: Tab 250mg, 500mg fully funded No-flam

TM

Tab 275mg, 550mg fully funded Sonaflam™, SynflexTM

Tab long-acting 750mg, lg fully funded Naprosyn SR

TM

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Drug Information

NORTRIPTYLINE (Norpress™) Class: antidepressant- tricyclic Indication: depression Unregistered indications: neuropathic pain Contraindications/cautions: arrhythmias, recent MI, epilepsy (lowers seizure threshold), urinary retention Undesirable effects: Very Common: Anticholinergic - dry mouth, blurred vision, urinary retention, drowsiness (tolerance to

these may develop except dry mouth) Common: Sweating, constipation, confusion, arrhythmias, tachycardia, postural hypotension. Interactions: CYP enzymes - metabolised by CYP2D6. May have increased concentrations with 2D6 inhibitors e.g. fluoxetine, haloperidol, paroxetine and valproate sodium. Risk of serotonin syndrome with other proserotonergic drugs e.g. SSRIs, carbamazepine. Alcohol, benzodiazepines - additive drowsiness Anticonvulsants - increased risk of seizures in epileptics Additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine) and opioids. Dosing: Depression, oral: 25-100mg at night (max of 50mg in elderly) Pain, oral: 10-50mg at night (start with low dose & titrate) S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Not really understood but thought to be through noradrenaline and serotonin in the CNS Onset: (depression): 2-6 weeks (pain): several days Availability: Tab 10mg, 25mg - fully funded (Norpress

TM)

Notes:

Metabolite of amitriptyline - less undesirable effects than amitriptyline & may be less sedating. 25mg nortriptyline = 75mg amitriptyline (approx)

60

Drug Information

NYSTATIN (Nilstat™) Class: antifungal - polyene Indication: fungal infections - topical, oral, gastrointestinal, vaginal Unregistered indications: Contraindications/cautions: Undesirable effects: Uncommon: Nausea, vomiting, diarrhoea (at high doses) Interactions: Dosing: Oral: (not absorbed orally) Oral candidiasis: 100,000 units (lml) four times a day Gastrointestinal candidiasis: 500,000 units four times a day S/C: not available Rectal: not available Topical: apply two to three times a day Vaginal: 1 pessary or 5g of cream once or twice a day Syringe driver: not available Mechanism of action: Increases fungal cell membrane permeability Availability: Oral suspension 100,000 unit/ml 24ml - fully funded Tabs, Caps 500,000 units - fully funded Pastille 100,000 units - not funded Paste 100,000 units/g 30g - not funded Topical cream 100,000 units/g 15g - partially funded Topical ointment 100,000 units/g 15g - not funded Vaginal cream 100,000 u/5g 75g, - partially funded Notes:

If infection is severe or recurrent use a systemic antifungal e.g. ketoconazole, fluconazole

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Drug Information

OCTREOTIDE (Sandostatin LAR™,OctreotideMaxRx) **Specialist/Hospice** Class: synthetic hormone Indications: Acromegaly, gastro-entero pancreatic endocrine tumours, post pancreatic surgery Unregistered indications: Inoperable bowel obstruction in cancer, reducing vomiting in palliative care, secretory diarrhoea, high fistula output, stopping variceal bleeding; ascites in cirrhosis and cancer; buccal fistula, death rattle; bronchorrhoea; reduction of tumour-related secretions (not funded for these indications) Contraindications/ cautions: hepatic impairment; diabetes Undesirable effects: Common: Injection site reaction, GI upset (nausea, abdominal pain, bloating, flatulence, diarrhoea),

dry mouth, hepatitis, gallstones, pancreatitis, hyper/hypoglycaemia, bradycardia, dizziness, drowsiness, headache, hypothyroidism

Interactions: May decrease absorption of cyclosporin Dosing: Oral: Not available S/C: 0.05-0.6mg/24 hours (max 1mg/24 hours). Varies according to indication. Rectal: Not available IV: Not available Syringe driver: Compatibilities unknown so give alone; diluent is normal saline. Mechanism of action: Synthetic analogue of somatostatin with a longer duration of action. It inhibits the secretion of insulin, glucagons, gastrin and other peptides of the gastr-enteropancreatic system, reducing splanchnic blood flow, portal blood flow, gastrointestinal motility, gastric, pancreatic and small bowel secretion, and increasing water and electrolyte absorption. Onset of action: 30 minutes Duration of action: 8 hours Availability: Inj 50 micrograms/ml lml - fully funded as below with Special Authority Inj 100 micrograms/ml lml - fully funded as below Inj 500 micrograms/ml lml - fully funded as below LAR 10mg * * fully funded pre-filled syringes, LAR 20mg *with Special Authority LAR 30mg * Full funding on Special Authority only for defined criteria. Specialist must make application; approvals are valid for 2 years. SA numbers for all forms are interchangeable. Notes:

The use of octreotide in patients with fistulae, oesophageal varices, miscelleneous diarrhoea and hypotension will not be funded as a special authority item.

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Drug Information

OLANZAPINE (Dr Reddy’s Olanzapine™, Olanzine™) Class: antipsychotic, antimanic, mood stabiliser Indication: acute and chronic psychoses including schizophrenia, acute mania, bipolar disorder Unregistered Indications: Nausea and vomiting, delirium Contraindications/cautions: Liver dysfunction, cardiovascular and cerebrovascular disease, hypotension, seizures, blood disorders, renal dysfunction, prostatic hypertrophy, paralytic ileus, bone marrow depression, diabetes, narrow angle glaucoma, hypercholesteraemia, Parkinsons disease Adverse reactions: Very common: drowsiness, weight gain, dizziness, hallucinations, akathisia and other extrapyramidal side

effects, oedema, elevated blood glucose and triglycerides, chest pain, constipation dry mouth

Less common: angioedema, urticaria, diabetic coma, hepatitis, pancreatitis, priapism, tardive dyskinesia, neuroleptic malignant syndrome, blood disorders, hypotension, mania, seizures

Metabolism/Clearance: Metabolised mainly in the liver by CYP1A2 and 3A4(minor) to inactive metabolites which are partially excreted by the kidneys Interactions:

Increased clinical effect/toxicity(due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors eg ketoconazole, ciprofloxacin, propranolol

Decreased clinical effect (due to decreased blood concentrations) may occur with some CYP metabolising enzyme inducers eg broccoli-like vegetables, cannabis, carbamazepine, cigarette smoke, omeprazole, phenobarbitone, phenytoin, rifampicin

Possibly increased risk of extrapyramidal effects with dopamine agonists eg metoclopramide

Additive hypotension with antihypertensives

Additive CNS effects with other CNS depressants eg benzodiazepines, phenothiazines, opioids, alcohol Dosing: oral tabs/ disp tabs, 2.5mg to 20mg per day as a single dose Subcut injection available but recommended for IM use only Rectal: not available Syringe Driver: not available Mechanism of Action: antagonises serotonin and dopamine receptors in the CNS Peak Effect: peak plasma concentration in 5-8 hours Duration: 21 – 54 hours (influenced by age, gender, smoking) Availability: Tablets 2.5mg, 5mg, 10mg Oral wafers 5mg, 10mg Inj 10mg Dose adjustment in renal impairment: caution needed Dose adjustment in hepatic impairment: no adjustment needed Notes:

Lower potential for neurological adverse effects than conventional antipyschotics

Increasingly used in acute delirium and behavioural disturbances associated with brain tumours

63

Drug Information

OMEPRAZOLE (Omezol Relief™, Dr Reddys Omeprazole™) Class: gastro-protective - proton pump inhibitor Indication: duodenal/gastric ulcer, reflux oesophagitis, acid dyspepsia Unregistered indications: Contraindications/cautions: renal impairment Undesirable effects: Common: Headache, nausea/vomiting, diarrhoea or constipation, flatulence Uncommon: Insomnia, dizziness, vertigo, pruritus, blood disorders, muscle/joint pain, dry mouth,

agitation Interactions:

CYP enzymes - metabolised by CYP3A4 and 2C19.

May have increased concentrations with CYP inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, and valproate sodium.

May have decreased concentrations with CYP inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin and prednisone.

May decrease concentrations of amitriptyline, ondansetron, warfarin and mexiletine.

May increase concentrations of amitriptyline, phenobarbitone, phenytoin and warfarin.

May decrease absorption of ketoconazole. Dosing: Oral: 10-40mg once a day, in the morning (max 20mg od in severe hepatic impairment) S/C: Injection available but not usually used Rectal: Not available Syringe driver: Not applicable Mechanism of action: Inhibits gastric acid secretion via proton pump blockade. Onset (antacid effect): oral 10-20 minutes Availability: Caps 10mg, 20mg, 40mg - fully funded Inj 40mg - fully funded Suspension (prepared by the pharmacy) - fully funded Notes:

Omeprazole is considered the drug of choice for prophylaxis or treatment of NSAID-induced GI damage.

Some patients may benefit from bd dosing (eg where higher doses used), or use of an H2-antagonist at night.

Patient Information: Take in the morning. Swallow whole or mix capsule contents in a slightly acidic fluid such as yoghurt or orange juice and take within 30 minutes. Alternatively, suck capsule and swallow pellets with liquid. Do not chew or crush capsules or pellets.

Oral suspension can be made by pharmacy if necessary

64

Drug Information

ONDANSETRON (Dr Reddy’s Ondansetron™, Ondansetron ODT-DRLATM, OnrexTM) Class: antiemetic - 5HT3 antagonist Indication: Nausea/vomiting post chemo- or radiotherapy, post-operative Unregistered indications: Intractable vomiting due to chemical, abdominal and cerebral causes when usual approaches have failed, opioid-induced pruritis, subcutaneous injection/infusion Contraindications/ cautions: hepatic impairment Undesirable effects: Very Common: Headache Common: Lightheadedness, nervousness, tremor, ataxia, asthenia, drowsiness, fever, sensation of

warmth or flushing, thirst, dizziness, constipation, diarrhoea. Interactions:

CYP enzymes.

May have increased concentrations with CYP inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, haloperidol, paroxetine and valproate sodium.

May have decreased concentrations with CYP inducers e.g. carbamazepine, dexamethasone, omeprazole, phenobarbitone, phenytoin and prednisone.

Dosing: Oral: 4-8mg twice a day S/C: Not usually used Rectal: Not available in NZ Syringe driver: compatibility unknown so don’t mix. Mechanism of action: Acts on 5HT3 receptors in the vomiting centre in the CNS & in the gut. Onset of action: <30 minutes (po) Duration of action: 12 hours Availability: Tab 4mg, 8mg, plain and dispersable - fully funded as below

65

Drug Information

OXYBUTYNIN (Apo-Oxybutynin™) Class: antimuscarinic (anticholinergic) Indication: frequency of micturation not caused by infective cystitis, bladder spasms Unregistered Indications: Contraindications: Glaucoma, myasthenia gravis, partial or complete GI obstruction, genitourinary obstruction, severe urinary retention, severe ulcerative colitis, hypersensitivity to drug, intestinal atony, megacolon, toxic megacolon Cautions: Use with caution in patients with urinary tract obstruction, angle-closure glaucoma, hyperthyroidism, elderly (anticholinergic effects – confusion, constipation, blurred vision, tachycardia), reflux oesophagitis, heart disease (IHD, CHF), hepatic or renal impairment, prostatic hypertrophy, hypertension Undesirable effects: Common: Drowsiness, dry mouth, constipation, nausea, abdominal discomfort, cognitive impairment

& delirium in the elderly Interactions: Additive sedative effects with CNS depressants and alcohol Additive anticholinergic effects with antihistamines and anticholinergic agents Dosing: Adults, 5mg bd Elderly, 2.5mg bd initially, increase to 5mg bd according to response & tolerance Syringe Driver: N/A Mechanism of Action: Direct antispasmodic effect on smooth muscle; also inhibits action of acetycholine on smooth muscle; does not block effects at skeletal muscle or at autonomic ganglia. Increases bladder capacity, decreases uninhibited contractions and delays desire to void; therefore decreases urgency and frequency. Onset of action: 30 to 60 minutes Duration of action: 6 to 10 hours Availability: Tab 5mg - fully funded Liquid 5mg/5ml - fully funded Dose adjustment in renal impairment: Eliminated renally; dose adjustment required Dose adjustment in hepatic impairment: Metabolised by liver; dose adjustment required

66

Drug Information

OXYCODONE (Oxy-Contin™ (slow release), Oxy-Norm™ (normal release), OxydoneTM), Oxycodone CR BNMTM (slow release) BNF Class: Opioid analgesic; semi-synthetic Indication: Moderate to severe pain in patients with cancer; postoperative pain, severe pain. Unlicensed Indications: An alternative in the case of intolerance to other strong opioids Contraindications/cautions: Sensitivity to oxycodone. Titrate carefully to patient’s pain. Undesirable effects: Very Common: (similar profile to other opioids) - constipation, dry mouth, nausea, vomiting, dizziness,

headache, orthostatic hypertension, pruritus, sweating, weakness, sedation. Common: confusion, hallucinations, bronchospasm, respiratory depression (see data sheet for

complete list) Interactions:

Like other opioids, oxycodone potentiates effects of tranquillisers, anaesthetics, hypnotics, sedatives, alcohol, muscle relaxants and antihypertensives.

CYP450-2D6 inhibitors (eg ketoconazole, erythromycin, quinidine, cimetidine) may inhibit metabolism of oxycodone resulting in increased oxycodone levels.

MAO inhibitors – CNS excitation or depression with hypertensive or hypotensive crisis. Avoid concurrent use of MAOIs or within 2 weeks of discontinuation of their use.

Dosing: PHARMAC prescribing guidelines state that morphine should be used first-line unless contraindicated. If converting a patient from morphine to oxycodone, please contact the Hospice Palliative Care Team for advice. Syringe Driver: Oxycodone ampoules 10mg amps 1 & 2 ml sizes are available for administration via a syringe driver Mechanism of Action: Oxycodone exerts opioid agonist actions similar to those of morphine and other opioid analgesics, primarily affecting the CNS and smooth muscle. Has affinity for kappa, mu and delta opioid receptors in brain & spinal cord. Pharmacological effects include analgesia (the principal thereapeutic action), anxiolysis, euphoria and feelings of relaxation. Also has anti-tussive actions. May be less hallucinogenic than morphine. Metabolised by the liver and excreted primarily in the urine. Onset of Action: 20-30 minutes (po) Duration of Action: 4-6 hours (12 hours sustained release) Plasma half-life: 3.5 hours (4.5 hours in renal failure) Oral bioavailability twice that of morphine due to less presystemic metabolism. Oxy-Contin™ - onset of analgesia within 1 hour in most patients and controlled delivery of oxycodone over 12 hours (biphasic delivery system with initial quick release then slow release over 12 hours). Dose adjustment in renal impairment: Renal impairment with CrCl < 60ml/min may result in decreased clearance and increased plasma concentrations of oxycodone – may need to reduce dose to one third or one half of the usual dose with cautious titration. Avoid if CrCl < 10ml/min. Dose adjustment in hepatic impairment: Metabolites do not contribute significantly to analgesic action but lower doses of oxycodone may be required in hepatic impairment due to increased plasma concentrations.

67

Drug Information

Availability: Caps 5mg, 10mg, 20mg – fully funded (Oxy-Norm™) (normal release) Tabs 5mg, 10mg, 20mg, 40mg, 80mg – fully funded (Oxy-Contin™, Oxydone BNM

TM)

(slow release) Oral liquid 5mg/5ml, 250ml OP Inj 10mg/ml, 1ml Inj 10mg/ml, 2ml All forms are fully funded Prescribing Guideline: Prescribers should note that oxycodone is significantly more expensive than long-acting morphine sulphate and clinical advice suggests that it is reasonable to consider this as a second-line agent to be used after morphine (PHARMAC). Notes:

Oxycodone is approximately one and a half to two times as potent as morphine sulphate (5mg oral oxycodone is approximately equivalent to 10mg oral morphine).

Oxy-Contin™ tablets are slow-release and must be swallowed whole, NOT broken, chewed or crushed. Taking broken, chewed or crushed tablets could lead to the rapid release and absorption of a potentially toxic dose of oxycodone.

Use Oxy-Norm™ for breakthrough pain – usually 20% of total daily dose as a breakthrough dose.

Females may have up to 25% higher plasma levels on a body-weight adjusted basis than males.

68

Drug Information

PAMIDRONATE DISODIUM (Pamisol™, Pamidronate BNMTM) **Specialist/Hospice** Class: bisphosphonate calcium regulator Indication: tumour-induced hypercalcaemia, Paget's disease, prophylactic use to reduce incidence of skeletal-related events in patients with osteolytic lesions from multiple myeloma, metastatic breast or prostate cancer. Unregistered indications: bone pain Contraindications/cautions: severe renal impairment Undesirable effects: Very common: Transient flu-like symptoms, slight increase in temperature, fever, hypocalcaemia,

transient bone pain, nausea, headache, fatigue, anxiety, hypertension, anaemia, cough, arthralgia, anorexia, nausea, vomiting, dyspepsia, abdominal pain, diarrhoea or constipation

Common: sleep disturbance, tachycardia, deterioration inrenal function, hypokalaemia Interactions: Loop diuretics - may cause electrolyte disturbances Dosing: Oral: Not available S/C: Not available Rectal: Not available IV infusion: Bone pain 90mg every 3-4 weeks Hypercalcaemia 15-90mg depending on serum Ca. * Rate of infusion should not exceed 1mg/minute and concentration should not exceed 60mg/250m1 Syringe driver: not applicable Mechanism of action: Inhibits bone resorption Onset of effect: Hypercalcaemia <3 days Duration of effect: Hypercalcaemia 2 weeks-3months, Bone pain 3-4 weeks Availability: Inj 3mg/ml, 5ml Fully funded Pamisol (delisting Dec 2014) Inj 3mg/ml, 10ml Fully funded Pamisol Inj 6mg/ml, 10ml Fully funded Pamisol Inj 9mg/ml, 10ml Fully funded Pamisol Special Authority (SA) for patients under hospice care who have tumour-induced hypercalcaemia or tumour-induced osteolysis without hypercalcaemia; specialist must apply. Also funded for Pagets disease. Approvals valid 2 years.

Notes:

50% of patients with metastatic bone pain may be responsive to pamidronate.

69

Drug Information

PANTOPRAZOLE (Pantoprazole Actavis™) Class: ulcer healing/prophylaxis - proton pump inhibitor Indication: Peptic ulceration, reflux oesophagitis, dyspepsia Unregistered indications: Contraindications/cautions: Renal impairment Undesirable effects: Common: Headache, nausea/vomiting, abdominal pain, flatulence, vomiting, diarrhoea or

constipation. Interactions:

CYP enzymes -may be metabolised by CYP2C19.

May have increased concentrations with e.g. fluconazole, fluoxetine, omeprazole and valproate sodium.

May have decreased concentrations with e.g. carbamazepine, dexamethasone and phenobarbitone.

May decrease the absorption of ketoconazole (due to pH-dependent bioavailability) Dosing: Oral: 20-80mg once a day S/C: Not available Rectal: Not available Syringe driver: Not applicable Mechanism of action: Inhibits gastric acid secretion via proton pump blockade. Onset (antacid effect): oral 2 hours Availability: Tabs 20mg, 40mg Fully funded Inj 40mg Not funded Notes: Swallow tablets whole, do not crush or chew.

70

Drug Information

PARACETAMOL (Pharmacare™, Parafast™, Ethics™, Paracare™) (In combination: CodcomolTM, PirophenTM, PanadeineTM, MersyndolTM, Paramax™, Paracetamol + Codeine (Relieve™) and others) Class: analgesic - non-opioid Indication: analgesic, antipyretic Unregistered indication: Contraindications/cautions: severe hepatic impairment Undesirable effects: Uncommon: Rash, pancreatitis on prolonged use, liver damage in overdose (> 6g in 24 hours) or

in combination with heavy alcohol intake, nephrotoxicity. Interactions:

Alcohol - decreased paracetamol metabolism

Warfarin - paracetamol may increase anticoagulant effect if given concurrently regularly for a long time.

Metoclopramide/domperidone - may increase absorption of paracetamol

Carbamazepine and phenytoin increase risk of hepatotoxicity Dosing: Oral: Adults 1000mg qid - not more than 4000mg/24hrs S/C: n/a Rectal: As for oral dose Syringe driver: not available Mechanism of action: Thought to have a central effect on pain pathways and not anti-inflammatory Onset: 0.5 hours Duration: 4 hours Availability: Tab 500mg fully funded Supp 500mg fully funded Liq 120mg/5ml, 250mg/5ml fully funded Soluble tab 500mg not funded Notes:

Give regularly rather than if required.

Combination tablets not recommended.

Liver damage may occur in overdose.

Not more than 4 doses (4000mg in adults) in 24hrs.

71

Drug Information

PAROXETINE (Loxamine™)

Class: SSRI Indication: Depressive illness, obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, generalised anxiety disorder Unregistered Indications: Contraindications/cautions: Contraindicated with MAOIs or if MAOIs used within 14 days and contraindicated with thioridazine; use in caution in patients with epilepsy (may affect seizure control), history of mania, renal disease, cardiac disease, suicidal patients Undesirable effects: Common: Dizziness, headache, insomnia, somnolence, constipation, diarrhoea, nausea, xerostomia,

weakness, yawning, postural hypotension Interactions:

Increased effect/toxicity: paroxetine should not be used with nonselective MAOIs – fatal reactions have been reported.

Avoid with phenothiazines – paroxetine may inhibit metabolism of thioridazine, resulting in increased plasma levels and possible arrhythmias; wait 5 weeks after stopping paroxetine before starting thioridazine

Increased risk of serotonin syndrome with amphetamines, buspirone, nefazadone, serotonin agonists (sumatriptan), other SSRIs, sympathomimetics, tramadol, carbamazepine, clozapine, dextromethorphan, carvedilol, digoxin, haloperidol, simvastatin, phenytion, tricyclic antidepressants, valproate.

Concurrent use of lithium may increase risk of nephrotoxicity Dosing: Adults: 20mg mane Elderly: Start with 10mg mane Syringe Driver: N/A Mechanism of Action: Selective serotonin reuptake inhibitor, chemically unrelated to other antidepressants; the inhibition of serotonin reuptake from brain synapse stimulated serotonin activity in the brain Pharmacokinetics: Metabolised extensively; half life 21 hours; metabolites excreted in bile and urine Availability: Tabs 20mg - fully funded Dose adjustment in renal impairment: reduce dose; 10mg mane Dose adjustment in hepatic impairment: reduce dose, 10mg mane

72

Drug Information

PHENOBARBITONE (Phenobarbitone tabs, PSM) **Specialist/Hospice** Class: anticonvulsant - barbiturate Indication: seizure control, status epilepticus Unregistered indications: terminal agitation Contraindications/cautions: Acute intermittent porphyria, elderly, renal/hepatic failure Undesirable effects: Very Common: Drowsiness, headache Common: GI upset, paradoxical excitement, pain, hypocalcemia, skin reactions Interactions:

CYP enzymes - metabolised by CYP2C so increased concentrations with 2C inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, miconazole, omeprazole and valproate sodium.

Decreased concentrations with 2C inducers e.g. carbamazepine, dexamethasone and phenytoin.

May decrease concentrations of amitriptyline, carbamazepine, clonazepam, dexamethasone, fentanyl, ketoconazole, methadone, miconazole, midazolam, NSAIDs, omeprazole, phenytoin, prednisone, risperidone, tramadol and warfarin.

Increased CNS depression with alcohol Dosing: Terminal agitation Oral: not used S/C: Dose titrated to need Rectal: not available Syringe driver: Give alone (do not mix with other drugs in syringe driver). Watch for irritation at injection site. Mechanism of action: Depresses activity of all excitable tissue perhaps via GABA. Availability: Inj 200mg/ml lml Section 29, not funded Tab 15mg, 30mg fully funded Notes:

Risk of respiratory depression in overdose.

73

Drug Information

MENTHOL 0.5% IN DP LOTION

Class: N/A Indication: Dry skin, pruritis Unregistered Indications: Contraindications/cautions: Do not apply to broken skin Undesirable effects: Interactions: Dosing: Apply up to four times daily as required Syringe Driver: N/A Mechanism of Action: Cooling & anti-pruritic emollient Peak Effect: Relief almost immediate Duration: Usually a few hours; variable Availability: Partially funded Dose adjustment in renal impairment: Dose adjustment in hepatic impairment: Notes:

May be useful in treating itch in hepatic impairment.

Compounded by pharmacist.

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Drug Information

PHENYTOIN (Dilantin™) Class: anticonvulsant Indication: epilepsy, trigeminal neuralgia Unregistered indications: neuropathic pain Contraindications/cautions: low albumin Undesirable effects: Common: Gingival hyperplasia, nausea, vomiting, constipation, insomnia, transient nervousness,

dizziness, headache, rash Interactions:

CYP enzymes - metabolised by CYP2C.

May have increased concentrations with 2C inhibitors e.g. fluconazole, fluoxetine, omeprazole, ketoconazole, metronidazole, miconazole and valproate sodium.

May have decreased concentrations with 2C inducers e.g. dexamethasone, carbamazepine and phenobarbitone.

May decrease concentrations of amitriptyline, carbamazepine, clonazepam, dexamethasone, fentanyl, ketoconazole, methadone, mexiletine, miconazole, midazolam, omeprazole, ondansetron, phenobarbitone, prednisone, risperidone, tramadol, NSAIDs, and warfarin.

Dosing: Oral: 100-300mg/24 hours S/C: Inj available but not given sc Rectal: Not available Syringe driver: Not applicable Mechanism of action: Inhibits spread of seizure through the motor cortex possibly via sodium channels Peak response: 7-10 days (if loaded - 8-12 hours) Availability: Tab 50mg fully funded Cap 30mg, 100mg fully funded Oral liq 30mg/ 5m1 fully funded Inj 50mg/ml, 2ml & 5ml fully funded Notes:

Monitor plasma concentrations.

Small dose increases may result in large plasma concentration increases.

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Drug Information

PREDNISONE (Apo-prednisone™) Class: corticosteroid - glucocorticoid Indication: allergy, asthma, rheumatic disease, inflammatory conditions Unregistered indications: Nausea/vomiting, inflammation in gastrointestinal obstruction, sweating, itch, hypercalcaemia, hiccup, pain, dyspnoea (lymphangitis), liver capsule pain, tenesmus Contraindications/cautions: Infections, gastrointestinal bleeding, diabetes, congestive heart failure, mood disorders Undesirable effects: Very Common: Insomnia (decrease by giving as single dose in the morning) Common: Sodium/ fluid retention, GI ulceration, delayed wound healing, thinning of skin (on

prolonged use), proximal muscle weakness, Cushings syndome, weight gain, depression, mania, delirium

Interactions:

CYP enzymes - metabolised by CYP3A4.

May have increased concentrations with 3A4 inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole and valproate sodium.

May have decreased concentrations with 3A4 inducers e.g. carbamazepine, dexamethasone, phenobarbitone and phenytoin.

May induce CYP3A4 so may decrease concentrations of drugs metabolised by it e.g. amitriptyline, clonazepam, dexamethasone, fentanyl, ketoconazole, methadone, miconazole, midazolam, omeprazole, risperidone, tramadol and warfarin.

Increased risk of GI bleed/ulceration when given with NSAIDs Dosing: Oral: 10-60mg in 24 hours S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Decreases inflammatory response thought to be via induction of lipocortin, an anti-inflammatory protein. Availability: Tab 1mg, 2.5mg, 5mg, 20mg, fully funded Notes:

0.75mg dexamethasone has an equivalent anti-inflammatory effect to 5mg prednisone or 20mg hydrocortisone.

On discontinuation decrease dose slowly (taper) unless the patient has been taking it for less than five days in which case dose tapering is not necessary.

Alteration in mood not usually seen below 40mg prednisone (6mg dexamethasone) per day.

Corticosteroid-induced insomnia responds to benzodiazepines (e.g. temazepam) but not to zopiclone.

Corticosteroid-induced mood disorder is usually depression and rarely mania.

May increase blood glucose levels

76

Drug Information

PROMETHAZINE (Aller-soothe™)

Class: antihistamine, phenothiazine derivative Indication: Nausea, vertigo, labyrinthine disorders, motion sickness, sedation (short-term use), symptomatic relief of allergy, pruritis Unregistered Indications: Contraindications/cautions: Use with caution in prostatic hypertrophy, urinary retention, and pyloroduodenal obstruction, hepatic & renal impairment, elderly may be more susceptible to side effects. Contraindicated in narrow angle glaucoma. Undesirable effects: Very Common: Sedation, drowsiness, dry mouth Common: Urinary retention, blurred vision, gastro-intestinal disturbances, headache, dizziness,

thickening of bronchial secretions Interactions:

CYP2D6 substrate.

Decreased effect possible with barbiturates, carbamazepine, benztropine

Increased effect: chloroquine, propranolol may increase promethazine concentrations; concurrent use with TCA may produce increased toxicity or altered therapeutic response; promethazine plus lithium may rearely produce nephrotoxicity. Concurrent use of promethazine and CNS depressants (narcotics) may produce additive depressant effects.

Dosing: Anti-emetic: 12.5mg – 25mg every four hours as needed (oral, IM, IV) Syringe Driver: Do not administer S/C – necrotic lesions may occur. Mechanism of Action: Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones; competes with histamine for the H1-receptor; reduces stimulti to the brainstem reticular system Peak Effect: Onset within 20 minutes Duration: 2-6 hours Availability: Tablet 10mg, 25mg Fully funded Oral Liquid 5mg/5ml Partially funded Inj 25mg/ml, 2ml Fully funded Dose adjustment in renal impairment: reduce dose Dose adjustment in hepatic impairment: Metabolised in the liver; dose adjustment required in hepatic impairment Notes:

Stability: Protect injection from light.

Compatible (when co-mixed in same syringe) with atropine, chlorpromazine, diphenhyramine, fentanyl, glycopyrrolate, midazolam.

Incompatible when mixed with frusemide, hydrocortisone, heparin, phenobarbital.

77

Drug Information

QUETIAPINE (Quetapel™, Dr Reddy’s Quetiapine™)

Class: antipsychotic - atypical Indication: acute and chronic psychoses including schizophrenia, manic episodes associated with bipolar disorder Unregistered Indications: nausea and vomiting, delirium, sedation Contraindications/cautions: liver dysfunction, cardiovascular and cerebrovascular disease, hypotension, seizures. Undesirable effects: Common: drowsiness, dry mouth, GI effects, tachycardia, dizziness, headache, agitation, insomnia,

weight gain, dyspepsia Less Common: neuroleptic malignant syndrome, tardive dyskinesia, cholesterol changes, thyroid hormone

changes, peripheral oedema, diabetes, extrapyramidal adverse effects, hepatotoxicity, blood disorders, postural hypotension, seizures, dyspnoea, sweating, rash

Interactions:

Increased clinical effect/toxicity of quetiapine (due to increased blood concentrations)may occur with some CYP metabolising enzyme inhibitors (see above) e.g. aprepitant, clarithromycin, fluconazole, fluoxetine, grapefruit juice, itraconazole, ketoconazole, valproate

Decreased clinical effect/toxicity of quetiapine (due to decreased blood concentrations) may occur with some CP metabolism enzyme inducers (see above) e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin, rifampicin, St John’s wort

Possible increase risk of extraphyramidal effects with dopamine antagonists e.g. metoclopramide

Additive hypotension with antihypertensives e.g. propranolol may occur

Additive CNS effects with other CNS depressants e.g benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), opioids, alcohol

Dosing:

Oral psychosis Initially 50mg/day increasing daily to 150mg to 750mg daily in 2 divided doses

mania Initially 100mg/day increasing daily to 200 to 800mg per day in 2 divided doses

Tranquillisation, sedation, anti-emetic

25mg to 100mg nocte

Subcut Not available

Rectal Not available

Syringe driver Not available

Mechanism of Action: Antagonises serotonin and dopamine receptors in the CNS Availability: Tab 25mg, 100mg, 200mg, 300mg Full funded Notes:

Lower potential for neurological advserse effects (e.g. extraphyramidal effects) than conventional antipsychotics

Increasingly used in acute delirium and behavourial distrubances associated with brain tumours.

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Drug Information

RANITIDINE (ZantacTM, Arrow-RanitidineTM, Pepti-soothe™, Ranitidine ReliefTM) Class: ulcer healing/prophylactic - H2 antagonist; gastro-protective Indication: duodenal/gastric ulcer, reflux oesophagitis, chronic episodic dyspepsia Unregistered indications: Subcutaneous injection/infusion, itch, sweating Contraindications/cautions: Caution in hepatic and renal impairment Undesirable effects: Common: Diarrhoea, tiredness, headache, dizziness, rash Interactions:

May increase anticoagulation effect of warfarin

May decrease the absorption of itraconazole and ketoconazole

May increase metformin concentrations

May increase concentrations of oral midazolam Dosing: Oral: 150mg twice a day or 300mg at night (reduce dose in elderly and renal impairment) S/C: 100-200mg/24 hours Rectal: Not available Syringe driver: See compatability chart. Not compatible with cyclizine at certain concentrations; not compatible with midazolam or sodium gardenal. Mechanism of action: Inhibits gastric acid secretion via histamine receptor blockade Onset of action: (acid supression): oral 10-20 minutes Duration of action: 8-12 hours Availability:

Tab 150mg, 300mg fully funded Arrow-RanitidineTM Ranitidine ReliefTM

Oral Liq 150mg/10ml fully

funded as below Pepti-sootheTM

Inj 25mg/ml 2ml fully funded Zantac

TM

Oral liquid requires endorsement, and is funded for oesophageal stricture, terminal care or patients who are too old or too young to swallow tablets. Prescription must be endorsed accordingly. Notes:

Omeprazole is considered the drug of choice for prophylaxis or treatment of NSAID-induced GI damage.

79

Drug Information

RISPERIDONE (RisperdalTM, Ridal™, Dr Reddy’s Risperidone™, Apo-Risperidone™, RisperonTM) Class: atypical antipsychotic Indication: acute & chronic psychosis Unregistered indications: delirium, poor response to or drug-induced movement disorders with haloperidol Contraindications/cautions: Monitor for hyperglycaemia, caution in hepatic & renal impairment, hypotension sensitive conditions, Parkinson's disease, elderly especially with dementia, cardio/cerebrovascular disease Undesirable effects: Common: Insomnia, agitation, anxiety, headache, drowsiness, weight gain, movement disorders Uncommon: Fatigue, dizziness, dydpepsia, nausea, vomiting, constipation, urinary incontinence

Interactions:

CYP enzymes - metabolised by CYP3A4 and 2D6.

May have increased concentrations with CYP inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, haloperidol, paroxetine and valproate sodium.

May have decreased concentrations with 3A4 inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin and prednisone

Possible increase risk of extrapyramidal effects with dopamine antagonists e.g. metoclopramide

Additive hypotension with antihypertensives Dosing: Oral: Start with 0.5mg bd; increase according to response IM: Inj every 2 weeks, initially 25mg Rectal: Not available Syringe driver: Not available Renal & Hepatic Impairment: Halve normal dose and slower dose titration recommended. Mechanism of action: Antagonises serotonin and dopamine receptors in the CNS Onset (psychosis): 1 - 2 weeks Availability: Tab FC 0.5mg, lmg, 2mg, 3mg, 4mg fully funded Tab, disintegrating 0.5mg, 1mg, 2mg fully funded Oral liquid lmg/ml fully funded, Risperon Inj IM 25mg, 37.5mg & 50mg funded with special authority Notes:

Lower potential for neurological adverse effects than conventional antipsychotics.

Increasingly used in acute delirium and behavioural disturbances associated with brain tumours.

At high dose (> 6-8mg a day) or in the cerebrally compromised patient, extrapyramidal side-effects may occur.

FC and oral disintegrating tablets are bioequivalent. Disintegrating tablets only funded under special authority – strict criteria apply.

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Drug Information

SALIVA SUBSTITUTE (Extemporaneous preparation)

Class: Artificial saliva Indication: Dry mouth (xerostomia) associated with salivary gland impairment, drug therapy, radiotherapy Unregistered Indications: Contraindications/cautions: Undesirable effects: Interactions: Dosing: Use as required Syringe Driver: N/A Mechanism of Action: local action of artificial saliva Peak Effect: Duration: Availability: Saliva Substitute, as per formula in the Pharmaceutical Schedule, is fully funded (maximum of 500ml per prescription) Dose adjustment in renal impairment: Dose adjustment in hepatic impairment: Notes:

Compounded by pharmacist.

Alternatives are available but may not be funded.

81

Drug Information

SENNA (SenokotTM, in combination with docusate, LaxsolTM) Class: laxative - stimulant Indication: constipation Unregistered indications: Contraindications/ cautions: Acute abdominal pain, intestinal obstruction Undesirable effects: Common: Abdominal cramps, diarrhoea, perianal irritation Uncommon: Atonic colon (with prolonged use), hypokalaemia, discolouration of urine (brown or pink) Interactions: May antagonise effects of antispasmodics e.g. hyoscine butylbromide Dosing: Oral: 2-4 tabs (14-28mg) at night (with docusate 1-2 tabs at night, max 4 tabs) S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Stimulates colonic activity via nerves in the intestinal mucosa. May also have stool softening properties Onset: 6-12 hours Availability: Tab 7.5mg Partially funded Senokot

TM

Tab 8mg (with 50mg docusate) Fully funded LaxsolTM

Notes:

May be useful in opioid induced constipation.

Only funded on prescription.

82

Drug Information

SODIUM ACID PHOSPHATE (Fleet Phosphate Enema™)

Class: Osmotic laxative Indication: Constipation; bowel evacuation before abdominal radiological procedures, endoscopy and surgery Unregistered Indications: Contraindications/cautions: Caution in elderly; contra-indicated in acute gastro-intestinal conditions; bowel obstruction Undesirable effects: Interactions: Dosing: Syringe Driver: Mechanism of Action: Peak Effect: Duration: Availability: Enema 16% with sodium phosphate 8% - funded on prescription only Dose adjustment in renal impairment: Dose adjustment in hepatic impairment:

83

Drug Information

SPIRONOLACTANE (SpirotoneTM, SpiractinTM) Class: diuretic - aldosterone antagonist, potassium sparing Indication: ascites & peripheral oedema associated with portal hypertension & hyperaldosteronism, congestive heart failure, primary aldosteronism Unregistered indications: Contraindications/cautions: Severe renal impairment, hyperkalaemia, anuria, Addisons disease Undesirable effects: Very Common: GI upset (anorexia, dyspepsia, nausea, vomiting, peptic ulceration, colic), CNS disturbances

(drowsiness, lethargy, confusion, headache, fever, ataxia, fatigue) Common: Hyperkalaemia, gynaecomastia, hyponatraemia Interactions:

Increased risk of hyperkalaemia with NSAIDs and ACE inhibitors (e.g. cilazapril, quinapril) and potassium supplements

Increases digoxin concentrations Dosing: Cirrhotic or malignant ascites: Oral: 100 - 200mg mane with food (max 400mg-600mg daily) Monitor body weight and renal function; consider adding furosemide 40mg mane if desired response not achieved with 400mg spironolactone. Syringe driver: not available Mechanism of action: Inhibits aldosterone causing natriuresis and potassium retention Onset of action: 2-4 hours; maximum effect 7 hours (single dose); 2-3 days (multiple doses) Duration of action: >24 hours (single dose), 2-3 days (multiple dose) Availability: Tab 25mg, 100mg fully funded Oral susp 5mg/ml fully funded * *Oral suspension only funded if prescription written by paediatrician, or other specialist if on the recommendation of a paediatrician or paediatric cardiologist. Notes:

Paracentesis may be necessary in malignant ascites

Monitor body weight and renal function.

84

Drug Information

TEMAZEPAM (Normison™) Class: Benzodiazepine, hypnotic, sedative Indication: Insomnia, treatment of anxiety and as an adjunct in the treatment of depression Unregistered Indications: Contraindications/cautions: Contraindicated in hypersensitivity to temazepam, severe uncontrolled pain, pre-existing CNS depression, narrow-angle glaucoma. Caution in children < 18 years of age, withdraw slowly in prolonged therapy, use with caution with other CNS depressants, in hepatic impairment and in the elderly Undesirable effects: Common: Anxiety, confusion, dizziness, drowsiness, euphoria, hangover, headache, vertigo, rash,

diarrhoea, weakness, blurred vision. Interactions: Alcohol and other CNS depressants may increase CNS effects of temazepam. Temazepam may decrease the antiparkinsonian effect of levodopa. Theophylline and other CNS stimulants may antagonize the sedative effects of temazepam. Dosing: 10mg to 20mg at night Syringe Driver: N/A Mechanism of Action: Benzodiazepine anxiolytic sedative that produces CNS depression; causes minimal change in REM sleep patterns. Peak Effect: Peak serum concentration in 2 to 3 hours. Metabolised in the liver; elimination 80 – 90% renally as inactive metabolites. Duration: Half-life 9.5 to 12.4 hours Availability: Tablets 10mg fully funded One month only per prescription Dose adjustment in renal impairment: No dose adjustment usually necessary Dose adjustment in hepatic impairment: Use lower dose Notes:

Capsules no longer available

Not available in 20mg

85

Drug Information

THIORIDAZINE (Thiondazine USP™)

** Specialist Hospice ** Class: antipsychotic, phenothiazine derivative Indication: management of psychotic disorders, depressive neurosis, schizophrenia Unregistered Indications: sweating

Contraindications: Severe CNS depression, hypersensitivity to phenothiazines, in combination with other medications known to prolong QT interval, history of cardiac arrhythmias, medications that inhibit metabolism of thioridazine (fluoxetine, paroxetine, propranolol, pindolol) Cautions: Narrow-angle glaucoma, severe liver or cardiac disease. Undesirable effects: Hypotension, peripheral oedema, arrhythmias, akathisia, tardive dyskinesia, dizziness, drowsiness, impairment of temperature regulation, photosensitivity, rash, skin discolouration, breast pain, constipation, weight gain, nausea, vomiting, diarrhoea, stomach pain, xerostomia, urinary retention, agranulocytosis, leukopenia, hepatotoxicity, tremor, seizures, pigmentary retinopathy, blurred vision, cornea and lens changes, nasal congestion. Interactions:

CYP1A2 and 2D6 enzyme substrate; CYP2D6 inhibitor.

Enzyme inducers may enhance metabolism of thioridazine – eg rifampicin, phenytoin, cigarette smoking.

Concurrent use with an antihypertensive may produce additive hypotensive effects; beta-blockers may increase risk of arrhythmia. Serum concentrations of carvedilol or valproate may be increased. Some quinolone antibiotics contraindicated with thioridazine due to arrhythmias (moxifloxacin).

Potassium depleting agents may increase risk of arrhythmias with thioridazine.

Metabolism may be decreased by amiodarone, cimetidine, fluoxetine, paroxetine, propafenone, ciprofloxacin – monitor for increased toxicity.

Dosing: Syringe Driver: N/A Mechanism of Action: Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones. Peak Effect: Time to peak serum concentration, within 1 hour Duration: 4 to 5 days Availability: Tablet 10mg Section 29, not funded Dose adjustment in renal impairment: not available Dose adjustment in hepatic impairment: Review dose in severe hepatic impairment Notes:

May discolour urine (pink or brown)

86

Drug Information

TRAMADOL (Arrow-Tramadol™, TramalTM) Class: analgesic - opioid-like (with extra effect on inhibitory pain pathways) Indication: Moderate to severe pain Unregistered use: subcutaneous injection/infusion Contraindications/cautions: Epilepsy, drug abuse, respiratory depression Undesirable effects: Very Common: N ausea, vomiting, diarrhoea, sweating - dose related Common: Dry mouth, sedation, headache, and hypertension Interactions:

CYP enzymes - metabolised by CYP2D6 (mainly).

May have increased concentrations with 2D6 inhibitors e.g. fluoxetine, haloperidol, paroxetine and valproate sodium.

CNS depressants - additive effects.

Risk of serotonin syndrome with other proserotonergic drugs e.g. tricyclic antidepressants, MAOIs, sumatriptan, SSRIs, pethidine, lithium, carbamazepine

Decreases seizure threshold so may interact with anticonvulsants. Dosing: Oral: 50 - 100mg 4 hourly (Max 400mg/24 hours) start with low dose to minimise Undesirable

effects S/C: Up to 400mg/24hours Rectal: Not available Syringe driver: give separately as compatibility as yet unknown Mechanism of action: Stimulates receptors in CNS and GIT and also affects noradrenaline and serotonin in descending spinal inhibitory pain pathways Peak effect (normal release oral): 0.5-1 hour Duration (normal release oral): 3-7 hours Availability: Caps 50mg - Fully funded Tabs SR 100mg, 150mg, 200mg - Fully funded Inj 50mg/ml 1ml, 100mg/2ml 2ml - Not funded Notes:

Place in palliative therapy still to be established.

May be useful in patients who are constipated on codeine/ morphine as it is less constipating.

Start with low dose to minimize adverse effects

Not a controlled drug; use standard prescription form.

87

Drug Information

TRANEXAMIC ACID (CyclokapronTM) Class: antifibrinolytic Indication: prevention of bleeding Unregistered indications: subarachnoid haemorrhage; surface bleeding from ulcerating tumours on the skin, nose, mouth & other organs Contraindications/cautions: Active thrombo-embolic disease, severe renal impairment Undesirable effects: Common: GI upset (nausea, vomiting, abdominal pain, diarrhoea) Interactions: may antagonise anticoagulants Dosing: Haemorrhage Oral: 1 - 1.5g three to four times a day S/C: Not used Rectal: The injection has been used rectally for rectal bleeding Topical: The injection has been used topically on bleeding wounds IV: 0.5 - 1g three times a day Syringe driver: Not applicable Mechanism action: Interacts with plasminogen to cause antifibrinolysis Peak effect: 3 hours Availability: Tab 500mg fully funded Inj 100mg/ml not funded Notes:

Tablets are large and patients may have difficulty swallowing them.

Tablets may be crushed and dispersed in water before swallowing.

88

Drug Information

TRIAMCINOLONE 0.1% IN ORABASE (Oracort™)

Class: corticosteroid for topical application – oral and perioral lesions Indication: treatment of oral ulceration and inflammation Unregistered Indications: Contraindications/cautions: Untreated oral infection; use contraindicated on tuberculous and viral lesions Undesirable effects: Occasional exacerbation of local infection Interactions: Dosing: Apply three to four times daily, after food Syringe Driver: N/A Mechanism of Action: Barrier protection of local area; reduction of inflammation and pain Peak Effect: Duration: Availability: Dental paste 0.1% - fully funded (Oracort™) Dose adjustment in renal impairment: Dose adjustment in hepatic impairment: Notes: press onto the affected area – do not rub

89

Drug Information

VALPROATE SODIUM (EpilimTM) Class: anticonvulsant Indication: epilepsy, bipolar disease Unregistered indications: neuropathic pain Contraindications/cautions: liver dysfunction Undesirable effects: Common: GI upset, tremor Uncommon: Thrombocytopenia, sedation, transient hair loss, hepatotoxicity Interactions:

CYP enzymes - inhibits many CYP enzymes - increases concentrations of many drugs - check individual drugs.

May be metabolised by CYP enzymes and may have decreased concentrations with carbamazepine. Dosing: Neuropathic pain Oral: 200-1000mg twice a day S/C: Available in injectable form, not usually used. Rectal: Not available Syringe driver: Not available Mechanism of action: In pain, as for carbamazepine Peak effect: Not known, peak concentrations reached in 4-8 hours Availability: Tab crushable 100mg - fully funded Tab EC 200mg, 500mg - fully funded Liq 200mg/5ml - fully funded (sugar free or syrup) Inj 100mg/ml (4ml) - fully funded Notes:

Co-analgesic often used with opioids in the treatment of neuropathic pain.

May be used in neuropathic pain when tricyclic antidepressants have failed or in combination with tricyclic antidepressants.

When switching from carbamazepine to sodium valproate, watch for toxicity from other drugs. Carbamazepine induces the metabolism of several drugs while sodium valproate inhibits the metabolism of several drugs.

Don't discontinue abruptly as risk of rebound seizures

Therapeutic drug monitoring is usually available.

Monitor LFTs.

Gabapentin may be more effective in neuropathic pain.

90

Drug Information

WARFARIN (CoumadinTM, MarevanTM)

Class: anticoagulant Indication: thrombotic disorders prophylaxis Unregistered indications: Contraindications/cautions: potential haemorrhagic conditions Undesirable effects: Common: bleeding Uncommon: hair loss, purple toe syndrome (rare) Interactions:

CYP enzymes.

May have increased concentrations with CYP inhibitors e.g. fluconazole, fluoxetine, ketoconazole, metronidazole, omeprazole, miconazole and valproate sodium.

May have decreased concentrations with CYP inducers e.g. carbamazepine, dexamethasone, phenobarbitone, phenytoin, cigarette smoke and prednisone.

Increased risk of bleeding with aspirin, SSRIs, NSAIDs.

Paracetamol may increase effect - any changes in drug therapy should be accompanied by an INR check. Dosing: Oral: Adjusted to INR (see below) S/C: Not available Rectal: Not available Syringe driver: Not available Mechanism of action: Interferes with Vitamin K synthesis Availability: Tab lmg, 2mg, 3mg, 5mg fully funded Notes:

Different brands are not proven to be equivalent – brands are not interchangeable.

Marevan – 1mg, 3mg, 5mg tabs Coumadin – 1mg, 2mg, 5mg tabs

Table from Management Guidelines for Common: Medical Conditions, 8th Edition 2000, Canterbury Health:

Treatment in DVT and PE INR Duration

Pre and perioperative anticoag. 1.5 – 2.0 Some days

Treatment of DVT 2.0 – 3.0 6-26 weeks

Treatment of PE or massive DVT 2.0 – 3.0 12-26 weeks

Treatment of recurrent DVT or PE* 3.0 – 4.0 ?life long

Atrial Fibrillation 2.0 – 3.0 Life long

Prosthetic heart valves 3.0 – 4.0 Life long

Arterial disease 3.0 – 4.0 Life long

* recurrence despite prothrombin ratio between 2 and 3

91

Drug Information

ZOPICLONE (Apo-Zopiclone™)

Class: hypnotic Indication: short-term treatment of insomnia Unregistered Indications: Contraindications/cautions: Caution in hepatic impairment (avoid if severe) and renal impairment; elderly, psychiatric illness, contraindicated in myasthenia gravis, respiratory failure, severe sleep apnoea syndrome, severe hepatic impairment Undesirable effects: Bitter or metallic taste, GI disturbances, nausea, vomiting, dry mouth, irritability, confusion, depressed mood, drowsiness, dizziness, incoordination, headache, urticaria, rash, hallucinations, nightmares, behavioural disturbances. Interactions: Increased sedative effect with other CNS depressants Dosing: 7.5mg at night (halve dose in elderly) Syringe Driver: N/A Mechanism of Action: Acts on benzodiazepine receptors Peak Effect: onset of action 30 – 60 minutes Duration: 6 to 8 hours Availability: Tablet 7.5mg fully funded One month only per prescription form Dose adjustment in renal impairment: Dose adjustment in hepatic impairment: Notes:

Not a benzodiazepine, but acts on the same receptors as benzodiazepines; drowsiness may persist the next day – caution with driving & using machinery

92

Drug Information

INDEX of DRUGS BY SYMPTOM **S/H = specialist/hospice

Anxiety Acute

Lorazepam Clonazepam

Chronic Fluoxetine

Bleeding (haemorrhage) Tranexamic acid

Constipation Softeners & stimulants - combination

Docusate & sennosides Danthron & poloxamer Docusate Movicol

Stimulants Bisacodyl

Rectal Phosphate enema (Fleet™)

Convulsions (seizures) Diazepam Valproate sodium Carbamazepine Phenytoin Clonazepam Midazolam

Cough Morphine The Mixture

“Death Rattle” (Terminal Respiratory Congestion) Hyoscine Glycopyrrolate (S/H)

Delirium (confusion) Haloperidol Risperidone Methotrimeprazine Olanzapine Quetiapine

93

Drug Information

Depression Fluoxetine Paroxetine Methylphenidate (S/H) Mitrazapine

Diarrhoea Codeine Loperamide Octreotide (S/H)

Dyspnoea (breathlessness) Morphine Midazolam Clonazepam Dexamethasone Prednisone

Hiccup Metoclopramide Nifedipine Valproate Antacids Baclofen Haloperidol

Insomnia Temazepam Zopiclone Clonazepam Quetiapine

Itch (pruritis) Promethazine Phenol/menthol in DP lotion

Mouth care

Mouthwashes Sodium bicarbonate (cleansing) Hydrogen peroxide (cleansing) Glycerin thymol (refreshing) Benzydamine (analgesic)

Saliva stimulants Iced pineapple chunks, lime juice Chewing gum

94

Drug Information

Saliva substitutes See pharmaceutical schedule for formulae

Anti-fungal agents Nystatin Miconazole Fluconazole (S/H)

Aphthous ulceration Triamcinolone in orabase

Nausea/vomiting

Higher centre stimulation (emotion – fear/anxiety) Lorazepam

Vomiting centre stimulation (radiotherapy to head, raised intracranial pressure) Cyclizine Dexamethasone

Vagal & sympathathetic afferent stimulation Hepatomegaly

Dexamethasone Cyclizine

Gastric stasis Metoclopramide Domperidone

Intestinal obstruction Cyclizine Methotrimeprazine

CTZ stimulation (uraemia, hypercalcaemia, drugs eg morphine) Haloperidol Methotrimeprazine Domperidone Metoclopramide Olanzapine

Vestibular nerve stimulation (motion) Cyclizine Hyoscine

Complicated/resistant Ondansetron (S/H)

Pain

Nociceptive (soft tissue) Paracetamol Codeine phosphate Diclofenac Ibuprofen

95

Drug Information

Tenoxicam Celecoxib Rofecoxib Tramadol Oxycodone Morphine Methadone Fentanyl (S/H) Ketamine (S/H)

Bone pain (with radiotherapy) Paracetamol Diclofenac Ibuprofen Tenoxicam Celecoxib Morphine Fentanyl (S/H) Pamidronate (S/H)

Neuropathic pain Antidepressants

Nortriptyline Amitriptyline Fluoxetine

Anticonvulsants Gabapentin (S/H) Valproate Carbamazepine

Antiarrhythmics Mexilitine Flecainaide

Others Dexamethasone Prednisone Clonidine Ketamine

Raised intracranial pressure Diclofenac Morphine Dexamethasone Prednisons

Liver capsule pain Dexamethasone Prednisone

Tenesmus (see constipation) Dexamethasone

96

5.3 Drug Information Continued Learning

Prednisone Nifedipine Opioids

Intestinal spasm Hyoscine butylbromide

Bladder spasm Oxybutynin Hyoscine butylbromide (high dose)

Restlessness (Terminal) – see pain, delerium, sedation

Sedation Midazolam Clonazepam Methotrimeprazine

Sweating Dexamethasone Prednisone Thioridazine

Ulcer prophylaxis Omeprazole Pantoprazole Ranitidine

Venous thromboembolism Enoxaparin

Wound care Metronidazole

Reference: The Palliative Care Handbook

97

Drug Information

Drugs by Generic Name

(S/H) specialist hospice supply

Amitriptyline

Baclofen

Benzydamine (analgesic) (S/H)

Bisacodyl

Carbamazepine

Celecoxib

Citalopram

Clonazepam

Clonidine

Codeine phosphate

Cyclizine

Danthron & poloxamer

Dexamethasone

Diazepam

Diclofenac

Docusate

Domperidone

Enoxaparin

Fentanyl

Flecainaide

Fluconazole

Fluoxetine

Gabapentin

Glycerin thymol

Glycopyrrolate (S/H)

Haloperidol

Hydrogen peroxide

Hyoscine

Hyoscine butylbromide

Ibuprofen

Ketamine (S/H)

Ketoconazole

Levomepromazine

Loperamide

Lorazepam

Methadone

Methylphenidate

Metoclopramide

Metronidazole

Miconazole

Microlax

Midazolam

Mirtazapine

Morphine

Movicol

Naproxen

Naloxone

Nifedipine

Nortriptyline

Nystatin

Octreotide

Olanzapine

Omeprazole

Ondansetron

Oxybutynin

Oxycodone

Pamidronate (S/H)

Pantoprazole

Paracetamol

Paroxetine

Phenobarbitone

Phenol/menthol in DP lotion

Phenytoin

Pholcodine

Phosphate Enema (FleetTM)

Prednisone

Promethazine

Quetiapine

Ranitidine

Risperidone

Rofecoxib

Saliva substitutes

Senna

Sodium bicarbonate mouthwash

Spironolactane

Temazepam

Thioridazine

Tramadol

Tranexamic acid

Triamcinolone in orabase

Valproate

Warfarin

Zopiclon

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