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Formulary 

Formulary
Chapter:
Formulary
Author(s):

Richard D.W. Hain

and Satbir Singh Jassal

DOI:
10.1093/med/9780198745457.003.0026
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Subscriber: null; date: 20 January 2020

Reproduced with permission of The Association of Paediatric Palliative Medicine © 2015

Adrenaline (topical)

Uses

Small external bleeds.

Dose and routes

Soak gauze in 1:1000 (1mg/mL) solution, and apply directly to bleeding point.

Alfentanil

Uses

  • Short-acting, synthetic, lipophilic, opioid analgesic derivative of fentanyl.

  • Used as analgesic, especially intraoperatively and for patients in intensive care and on assisted ventilation (adjunct to anaesthesia).

  • Alternative opioid if intolerant to other strong opioids; useful in renal failure if neurotoxic on morphine, or stages 4–5 severe renal failure.

  • Useful for breakthrough pain and procedure-related pain.

Dose and routes

  • Analgesic, especially intraoperatively and for patients in intensive care and on assisted ventilation (adjunct to anaesthesia). SEEK SPECIALIST ADVICE.

  • By iv/sc bolus (these doses assume assisted ventilation is available):

    • neonate: 5–20 micrograms/kg initial dose, supplemental doses up to 10 micrograms/kg;

    • 1 month to 18 years: 10–20 micrograms/kg initial dose, up to 10 micrograms/kg supplemental doses.

  • By continuous iv or sc infusion (these doses assume assisted ventilation is available):

    • neonate: 10–50 micrograms/kg over 10min, then 30–60 micrograms/kg/h;

    • 1 month to 18 years: 50–100 micrograms/kg loading dose over 10min, then 30–60 micrograms/kg/h as a continuous infusion.

  • Alternative opioid if intolerant to other strong opioids; useful in renal failure if neurotoxic on morphine, or stages 4–5 severe renal failure. SEEK SPECIALIST ADVICE.

  • Doses should be based on opioid equivalence, with the following suggested as safe and practical conversion ratios.

  • po morphine to continuous subcutaneous infusion (CSCI) alfentanil: 1/30th of the 24h total po morphine dose, e.g. 60mg/24h po morphine = 2mg/24h CSCI alfentanil.

  • CSCI/iv morphine to CSCI alfentanil: 1/15th of the 24h total CSCI/iv morphine dose, e.g. 30mg/24h CSCI/iv morphine = 2mg/24h CSCI alfentanil.

  • CSCI diamorphine to CSCI alfentanil: 1/10th of the 24h total diamorphine dose, e.g. 30mg/24h diamorphine = 3mg/24h CSCI alfentanil.

  • If conversion is due to toxicity of the previous opioid, lower doses of alfentanil may be needed to provide adequate analgesia.

  • Opioid-naïve adults: CSCI 500 micrograms to 1mg over 24h.

Breakthrough pain

SEEK SPECIALIST ADVICE.

  • sc/sublingual/buccal.

  • Suggest 1/6th to 1/10th of the total CSCI dose. However, there is a poor relationship between the effective prn dose and the regular background dose. Alfentanil has a short duration of action (~30min), and, even with an optimally titrated prn dose, frequent dosing (even every 1–2h) may be required. Dose and frequency of administration should be regularly reviewed.

Procedure-related pain

SEEK SPECIALIST ADVICE.

  • sc/sublingual/buccal.

  • Adults: 250–500 micrograms, single dose.

  • Child: 5 micrograms/kg, single dose.

Give dose 5min before an event likely to cause pain; repeat, if needed.

Notes

  • Alfentanil injection is licensed for use in children as an analgesic supplement for use before and during anaesthesia. Use for pain relief in palliative care is unlicensed. Buccal, sublingual, or intranasal administration of alfentanil for incident/breakthrough pain is an unlicensed indication and route of administration. The injection solution may be used for buccal, sublingual, or intranasal administration (unlicensed).

  • There is limited information/evidence for analgesic doses in palliative care, especially in children. Doses are largely extrapolated from suggested equianalgesic doses with other opioids.

  • Potency: 10–20 times stronger than parenteral morphine, ~25% of the potency of fentanyl.

  • Very useful in patients with severe renal failure (no dose reduction is needed). May need to reduce the dose in severe hepatic impairment.

  • In order to avoid excessive dosage in obese children, the dose may need to be calculated on the basis of ideal weight for height, rather than actual weight.

  • Pharmacokinetics: half-life is prolonged in neonates, so can accumulate in prolonged use. Clearance may be increased from 1 month to 12 years of age, so higher infusion doses may be needed.

  • Contraindication: not to be administered concurrently with monoamine oxidase inhibitors (MAOIs) or within 2 weeks of their discontinuation.

  • Interaction: alfentanil levels are increased by inhibitors of cytochrome P450.

  • Adverse effects include respiratory depression, hypotension, hypothermia, muscle rigidity (which can be managed with neuromuscular-blocking drugs).

  • For sc or iv infusion, alfentanil is compatible with 0.9% sodium chloride (NaCl) or 5% glucose as a diluent. For CSCI alfentanil, appears compatible with most drugs used in a syringe driver. Like diamorphine, high doses of alfentanil may be dissolved in small volumes of diluent, which is very useful for sc administration.

  • Available as: injection (500 micrograms/mL in 2mL and 10mL ampoules); intensive care injection (5mg/mL in 1mL ampoules which must be diluted before use). Nasal spray with attachment for buccal/sublingual use (5mg/5mL bottle available as special order from Torbay Hospital: each ‘spray’ delivers 0.14mL = 140 micrograms alfentanil).

Amitriptyline

Uses

  • Neuropathic pain.

Dose and routes

By mouth

  • Child 2–12 years: initial dose of 200 micrograms/kg (maximum 10mg), given od at night. Dose may be increased gradually, if necessary, to a suggested maximum of 1mg/kg/dose twice daily (bd) (under specialist supervision).

  • Child 12–18 years: initial dose of 10mg at night, increased gradually, if necessary, every 3–5 days to a suggested initial maximum of 75mg/day. Higher doses up to 150mg/day in divided doses may be used under specialist advice.

Notes

  • Not licensed for use in children with neuropathic pain.

  • Analgesic effect unlikely to be evident for several days. Potential improved sleep and appetite which are likely to precede analgesic effect.

  • Drug interactions: not to be administered concurrently with MAOIs or within 2 weeks of their discontinuation. Caution with concurrent use of drugs which inhibit or induce CYP2D6 enzymes.

  • Main side effects limiting use in children include constipation, dry mouth, and drowsiness.

  • Liquid may be administered via an enteral feeding tube.

  • Available as: tablets (10mg, 25mg, 50mg) and oral solution (25mg/5mL, 50mg/5mL).

Aprepitant

Uses

  • Prevention and treatment of nausea and vomiting associated with emetogenic cancer chemotherapy.

Dose and routes

For oral administration

  • Child <10 years: 3mg/kg (max 125mg) as a single dose on Day 1 (1h before chemotherapy), followed by 2mg/kg (max 80mg) as a single dose on Day 2 and Day 3.

  • Child >10 years: 125mg as a single dose on Day 1 (1h before chemotherapy), followed by 80mg as a single dose on Day 2 and Day 3.

Aprepitant is used in combination with a corticosteroid (usually dexamethasone) and a 5HT3 antagonist such as ondansetron.

Notes

  • Aprepitant is licensed for the prevention of acute and delayed nausea and vomiting associated with highly or moderately emetogenic cancer chemotherapy in adults.

  • Aprepitant is not licensed for use in children and adolescents less than 18 years of age (although a number of clinical trials are currently ongoing). Limited evidence for use in those less than 10 years of age.

  • Aprepitant is a selective high-affinity antagonist at NK1 receptors.

  • Aprepitant is a substrate, a moderate inhibitor, and inducer of the CYP3A4 isoenzyme system. It is also an inducer of CYP2C9 and therefore has the potential to interact with any other drugs that are also metabolized by these enzyme systems, including rifampicin, carbamazepine, phenobarbital, itraconazole, clarithromycin, warfarin, and dexamethasone. Please note this list is not exhaustive—seek advice.

  • Common side effects include hiccups, dyspepsia, diarrhoea, constipation, anorexia, asthenia, headache, and dizziness.

  • Available as: capsules 80mg and 125mg. A formulation for extemporaneous preparation of an oral suspension is available.

Arachis oil enema

Uses

  • Faecal softener.

  • Faecal impaction.

Dose and routes

By rectal administration

  • Child 3–7 years: 45–65mL as required (~1/3 to 1/2 enema).

  • Child 7–12 years: 65–100mL as required (~1/2 to 3/4 enema).

  • Child 12 years and over: 100–130mL as required (~3/4 to 1 enema).

Notes

  • Caution: as arachis oil is derived from peanuts, do not use in children with a known allergy to peanuts.

  • Generally used as a retention enema to soften impacted faeces. May be instilled and left overnight to soften the stool.

  • Warm the enema before use by placing in warm water.

  • Administration may cause local irritation.

  • Licensed for use in children from 3 years of age.

  • Available as: enema, arachis (peanut) oil in 130mL single-dose disposable packs.

Aspirin

Uses

  • Mild to moderate pain.

  • Pyrexia.

Dose and routes

By mouth

  • >16 years of age: initial dose of 300mg every 4–6h when necessary. Dose may be increased, if necessary, to a maximum of 900mg every 4–6h (maximum 4g/day).

Notes

  • Contraindicated in children due to risk of Reye’s syndrome.

  • Use with caution in asthma, previous peptic ulceration, severe hepatic or renal impairment.

  • May be used in low dose under specialist advice for children with some cardiac conditions.

  • Available as: tablets (75mg, 300mg), dispersible tablets (75mg, 300mg), and suppositories (150mg available from special-order manufacturers or specialist importing companies).

Baclofen

Uses

  • Chronic severe spasticity of voluntary muscle.

  • Considered as third-line neuropathic agent.

Dose and routes

By mouth

  • Initial dose for child under 18 years: 300 micrograms/kg/day in four divided doses (maximum single dose 2.5mg), increased gradually at weekly intervals to a usual maintenance dose of 0.75–2mg/kg/day in divided doses, with the following maximum daily doses:

    • child up to 8 years: maximum total daily dose 40mg/day;

    • child 8–18 years: maximum total daily dose 60mg/day.

Notes

  • Review treatment if no benefit within 6 weeks of achieving maximum dose.

  • There are very limited clinical data on the use of baclofen in children under the age of 1 year. Use in this patient population should be based on the physician’s consideration of individual benefit and risk of therapy.

  • Monitor and review reduction in muscle tone and potential adverse effects on swallow and airway protection.

  • Avoid abrupt withdrawal.

  • Intrathecal use by specialist only.

  • Risk of toxicity in renal impairment; use smaller oral doses and increase dosage interval, if necessary.

  • Contraindicated if there is a history of active peptic ulceration.

  • Administration with or after food may minimize gastric irritation.

  • May be administered via enteral feeding tubes. Use a liquid formulation for small doses; dilute prior to use to reduce viscosity. Consider dispersing tablets in water for higher doses, owing to the sorbitol content of the liquid formulation.

  • Available as: tablets (10mg) and oral solution (5mg/5mL).

Bethanechol

Uses

  • Opioid-induced urinary retention.

Dose and routes

By mouth

  • Child over 1 year: 0.6mg/kg/day in three or four divided doses. Maximum single dose 10mg.

  • Adult dose: 10–25mg per dose 3–4 times a day. Occasionally, it may be felt necessary to initiate therapy with a 50mg dose.

Subcutaneous

  • Child over 1 year: 0.12–2mg/kg/day in three or four divided doses. Maximum single dose 2.5mg.

  • Adult dose: 2.5–5mg per dose 3–4 times a day.

Notes

  • The safety and efficacy of bethanechol in children have not been established (bethanechol is not licensed for use in children).

  • Preferably taken before food to reduce the potential for nausea and vomiting.

  • Contraindicated in hyperthyroidism, peptic ulcer, asthma, cardiac disease, and epilepsy.

  • Tablets may be crushed and dispersed in water for administration via an enteral feeding tube; a formulation for extemporaneous oral suspension is available.

  • Available as: tablets (10mg and 25mg), injection for sc injection only (5mg/mL—not licensed in the UK but may be possible to import via a specialist importation company).

Bisacodyl

Uses

  • Constipation.

Dose and routes

By mouth

  • Child 4–18 years: 5–20mg od; adjust according to response.

By rectum (suppository)

  • Child 2–18 years: 5–10mg od; adjust according to response.

Notes

  • Tablets act in 10–12h. Suppositories act in 20–60min; suppositories must be in direct contact with the mucosal wall.

  • Stimulant laxative.

  • Prolonged or excessive use can cause electrolyte disturbance.

  • Available as: tablets (5mg) and suppositories (5mg, 10mg).

Buprenorphine

Uses

  • Moderate to severe pain.

Dose and routes

By sublingual route (starting doses)

  • Child body weight 16–25kg: 100 micrograms every 6–8h.

  • Child body weight 25–37.5kg: 100–200 micrograms every 6–8h.

  • Child body weight 37.5–50kg: 200–300 micrograms every 6–8h.

  • Child body weight over 50kg: 200–400 micrograms every 6–8h.

By transdermal patch

  • By titration or as indicated by existing opioid needs.

Buprenorphine patches are approximately equivalent to the following 24h doses of po morphine.

Morphine salt 12mg daily

BuTrans® ‘5’ patch

7-day patches

Morphine salt 24mg daily

BuTrans® ‘10’ patch

7-day patches

Morphine salt 48mg daily

BuTrans® ‘20’ patch

7-day patces

Morphine salt 84mg daily

Transtec® ‘35’ patch

4-day patches

Morphine salt 126mg daily

Transtec® ‘52.5’ patch

4-day patches

Morphine salt 168mg daily

Transtec® ‘70’ patch

4-day patches

Notes

  • Sublingual tablets not licensed for use in children <6 years old.

  • Patches not licensed for use in children.

  • Has both opioid agonist and antagonist properties, and may precipitate withdrawal symptoms, including pain, in children dependent on high doses of other opioids.

  • Sublingual duration of action 6–8h.

  • Caution with hepatic impairment and potential interaction with many drugs, including antiretrovirals.

  • Available as tablets (200 micrograms, 400 micrograms) for sublingual administration. Tablets may be halved.

  • Available as three types of patches:

    • BuTrans®—applied every 7 days. Available as 5 (5 micrograms/h for 7 days),10 (10 micrograms/h for 7 days), and 20 (20 micrograms/h for 7 days);

    • Transtec®—applied every 96h. Available as 35 (35 micrograms/h for 96h), 52.5 (52.5 micrograms/h for 96h), and 70 (70 micrograms/h for 96h).

    • Hapoctasin®—available as 35, 52.5 and 70 micrograms/h for 72 hours.

  • For patches, systemic analgesic concentrations are generally reached within 12–24h, but levels continue to rise for 32–54h. If converting from:

    • 4-hourly po morphine—give regular doses for the first 12h after applying the patch;

    • 12-hourly slow-release morphine—apply the patch, and give the final slow-release dose at the same time;

    • 24-hourly slow-release morphine—apply the patch 12h after the final slow-release dose;

    • CSCI—continue the syringe driver for about 12h after applying the patch.

  • Effects only partially reversed by naloxone.

  • Rate of absorption from patches is affected by temperature, so caution with pyrexia or increased external temperature such as hot baths—possibility of accidental overdose, with respiratory depression.

  • Patches are finding a use as an easily administered option for low-dose background opioid analgesia in a stable situation, for example in severe neurological impairment.

  • Schedule 3 controlled drug (CD).

Carbamazepine

Uses

  • Neuropathic pain.

  • Some movement disorders.

  • Anticonvulsant.

Dose and routes

By mouth

  • Child 1 month to 12 years: initial dose of 5mg/kg at night or 2.5mg/kg bd, increased, as necessary, by 2.5–5mg/kg every 3–7 days, usual maintenance dose; 5mg/kg 2–3 times daily. Doses up to 20mg/kg/day in divided doses have been used.

  • Child 12–18 years: initial dose of 100–200mg 1–2 times daily; increased slowly to usual maintenance of 200–400mg 2–3 times daily. Maximum 1.8g/day in divided doses.

By rectum

  • Child 1 month to 18 years: use ~25% more than the oral dose (maximum single dose 250mg) up to four times daily (qds).

Notes

  • Not licensed for use in children with neuropathic pain.

  • Can cause serious blood, hepatic, and skin disorders. Parents should be taught how to recognize signs of these conditions, particularly leucopenia.

  • Numerous interactions with other drugs, including chemotherapy drugs.

  • Different preparations may vary in bioavailability, so avoid changing formulations or brands.

  • Suppositories of 125mg are approximately equivalent to 100mg tablets.

  • Oral liquid has been administered pr—should be retained for at least 2h, if possible, but may have a laxative effect.

  • For administration via an enteral feeding tube, use the liquid preparation. Dilute with an equal volume of water immediately prior to administration. If giving doses higher than 400mg/day, divide into four equal doses.

  • Available as: tablets (100mg, 200mg, 400mg), chew tablets (100mg, 200mg), liquid (100mg/5mL), suppositories (125mg, 250mg), and modified-release tablets (200mg, 400mg).

Celecoxib

Uses

  • Pain, inflammatory pain, bone pain, stiffness. Not used first-line.

  • Dose based on management of juvenile rheumatoid arthritis.

Dose and routes

By mouth

  • Child over 2 years:

    • weight 10–25kg: 50mg bd or 100mg daily;

    • weight >25kg: 100mg bd.

Notes

  • Celecoxib is a cyclo-oxygenase-2 (COX-2) selective inhibitor.

  • Not licensed in the UK for use in children.

  • All NSAID use (including COX-2 selective inhibitors) can, to varying degrees, be associated with a small increased risk of thrombotic events (e.g. myocardial infarction and stroke), independent of baseline cardiovascular risk factors or duration of NSAID use; however, the greatest risk may be in those receiving high doses long-term. COX-2 inhibitors are associated with an increased risk of thrombotic effects.

  • All NSAIDs are associated with serious gastrointestinal toxicity. COX-2 inhibitors are associated with a lower risk of serious upper gastrointestinal side effects than non-selective NSAIDs.

  • Use with caution in patients with renal impairment, and avoid in severe renal impairment.

  • Use with caution in hepatic impairment.

  • Celecoxib interacts with a great many commonly used drugs; check the British National Formulary (BNF) (current version online).

  • Capsules may be opened, and contents mixed with soft food immediately before administration. For a 50mg dose, approximately halve the 100mg capsule contents to give the best estimate of a 50mg dose.

  • Available as: capsules 100mg, 200mg.

Chloral hydrate

Uses

  • Insomnia.

  • Agitation.

Dose and routes

By mouth or rectum

  • Neonate: initial dose of 30mg/kg as a single dose at night. May be increased to 45mg/kg at night or when required.

  • Child 1 month to 12 years: initial dose of 30mg/kg as a single dose at night. May be increased to 50mg/kg at night or when required. Maximum single dose 1g.

  • Child 12–18 years: initial dose of 500mg as a single dose at night or when required. Dose may be increased, if necessary, to 1–2g. Maximum single dose 2g.

Notes

  • Not licensed in agitation or in infants <2 years for insomnia.

  • Oral use: mix with plenty of juice, water, or milk to reduce gastric irritation and disguise the unpleasant taste.

  • For rectal administration, use oral solution or suppositories (available from ‘specials’ manufacturers).

  • Accumulates on prolonged use and should be avoided in severe renal or hepatic impairment.

  • Available as: tablets (chloral betaine 707mg = choral hydrate 414mg—Welldorm®), oral solution (143.3mg/5mL—Welldorm®; 200mg/5mL, 500mg/5mL, both of which are available from ‘specials’ manufacturers or specialist importing companies), and suppositories (available as various strengths—25mg, 50mg, 60mg, 100mg, 200mg, 500mg, from ‘specials’ manufacturers).

Chlorpromazine

Uses

  • Hiccups.

  • Nausea and vomiting of terminal illness (where other drugs are unsuitable).

Dose and routes

Hiccups

By mouth

  • Child 1–6 years: 500 micrograms/kg every 4–6h, adjusted according to response (maximum 40mg daily).

  • Child 6–12 years: 10mg three times daily (tds), adjusted according to response (maximum 75mg daily).

  • Child 12–18 years: 25mg tds (or 75mg at night), adjusted according to response; higher doses may be used by specialist units.

Nausea and vomiting of terminal illness (where other drugs are unsuitable)

By mouth

  • Child 1–6 years: 500 micrograms/kg every 4–6h; maximum 40mg daily.

  • Child 6–12 years: 500 micrograms/kg every 4–6h; maximum 75mg daily.

  • Child 12–18 years: 10–25mg every 4–6h.

By deep intramuscular injection

  • Child 1–6 years: 500 micrograms/kg every 6–8h; maximum 40mg daily.

  • Child 6–12 years: 500 micrograms/kg every 6–8h; maximum 75mg daily.

  • Child 12–18 years: initially 25mg, then 25–50mg every 3–4h until vomiting stops.

Notes

  • Not licensed in children for intractable hiccup.

  • Caution in children with hepatic impairment (can precipitate coma), renal impairment (start with a small dose; increased cerebral sensitivity), cardiovascular disease, epilepsy (and conditions predisposing to epilepsy), depression, and myasthenia gravis.

  • Caution is also required in severe respiratory disease and in children with a history of jaundice or who have blood dyscrasias (perform blood counts if unexplained infection or fever develops).

  • Photosensitization may occur with higher dosages; children should avoid direct sunlight.

  • Antipsychotic drugs may be contraindicated in CNS depression.

  • Risk of contact sensitization; tablets should not be crushed, and solutions should be handled with care.

  • Available as: tablets, coated (25mg, 50mg, 100mg); oral solution (25mg/5mL, 100mg/5mL); injection (25mg/mL in 1mL and 2mL ampoules).

Clobazam

Uses

  • Adjunctive therapy for epilepsy.

Dose and routes

For oral administration

  • Child 1 month to 6 years: initial dose of 125 micrograms/kg bd. Increase every 5 days, as necessary and as tolerated, to a usual maintenance dose of 250 micrograms/kg bd. Maximum dose 500 micrograms/kg (15mg single dose) bd.

  • Child 6–18 years: initial dose of 5mg daily. Increase every 5 days, as necessary and as tolerated, to a usual maintenance dose of 0.3–1mg/kg daily. Maximum 60mg daily. Daily doses of up to 30mg may be given as a single dose at bedtime; higher doses should be divided.

Notes

  • Not licensed for use in children <6 years of age.

  • Once titrated to an effective dose of clobazam, patients should remain on their treatment, and care should be exercised when changing between different formulations.

  • Tablets can be administered whole, or crushed and mixed in apple sauce. The 10mg tablets can be divided into equal halves of 5mg. Clobazam can be given with or without food.

  • Possible side effects as would be expected from benzodiazepines. Children are more susceptible to sedation and paradoxical emotional reactions.

  • Available as: tablets (10mg Frisium®), tablets (5mg—unlicensed and available on a named-patient basis), and oral liquid (5mg in 5mL and 10mg in 5mL—care with differing strengths).

  • Frisium® tablets are NHS-blacklisted, except for epilepsy and endorsed ‘SLS’.

Clonazepam

Uses

  • Tonic–clonic seizures.

  • Partial seizures.

  • Cluster seizures.

  • Myoclonus.

  • Status epilepticus (third-line, particularly in neonates).

  • Neuropathic pain.

  • Restless legs.

  • Gasping.

  • Anxiety and panic.

Dose and routes

By mouth (anticonvulsant doses: reduce for other indications)

  • Child 1 month to 1 year: initially 250 micrograms at night for four nights, increased over 2–4 weeks to usual maintenance dose of 0.5–1mg at night (may be given in three divided doses, if necessary).

  • Child 1–5 years: initially 250 micrograms at night for four nights, increased over 2–4 weeks to usual maintenance of 1–3mg at night (may be given in three divided doses, if necessary).

  • Child 5–12 years: initially 500 micrograms at night for four nights, increased over 2–4 weeks to usual maintenance dose of 3–6mg at night (may be given in three divided doses, if necessary).

  • Child 12–18 years: initially 1mg at night for four nights, increased over 2–4 weeks to usual maintenance of 4–8mg at night (may be given in three divided doses, if necessary).

For status epilepticus

Continuous subcutaneous infusion

  • Child 1 month to 18 years: starting dose 20–25 micrograms/kg/24h.

  • Maximum starting doses: 1–5 years: 250 micrograms/24h; 5–12 years: 500 micrograms/24h.

  • Increase at intervals of not less than 12h to 200 micrograms/kg/24h (maximum 8mg/24h).

  • Doses of up to 1.4mg/kg/24h have been used in status epilepticus in PICU environment.

By intravenous injection over at least 2min, or infusion

  • Neonate: 100 micrograms/kg iv over at least 2min, repeated after 24h if necessary (avoid unless no safer alternative). Used for seizures not controlled with phenobarbital or phenytoin.

  • Child 1 month to 12 years: loading dose 50 micrograms/kg (maximum 1mg) by iv injection, followed by iv infusion of 10 micrograms/kg/h, adjusted according to response; maximum 60 micrograms/kg/h.

  • Child 12–18 years: loading dose 1mg by iv injection, followed by iv infusion of 10 micrograms/kg/h, adjusted according to response; maximum 60 micrograms/kg/h.

Notes

  • Licensed for use in children for status epilepticus and epilepsy. Not licensed for neuropathic pain. Tablets licensed in children.

  • Very effective anticonvulsant, usually third-line due to side effects and development of tolerance.

  • Use lower doses for panic, anxiolysis, terminal sedation, neuropathic pain, and restless legs.

  • Do not use in acute or severe respiratory insufficiency, unless in the imminently dying. Be cautious in those with chronic respiratory disease.

  • As an anxiolytic/sedative, clonazepam is ~20 times as potent as diazepam (i.e. 250 micrograms of clonazepam equivalent to 5mg of diazepam po).

  • Multiple indications, in addition to anticonvulsant activity, can make clonazepam particularly useful in the palliative care of children for neurological disorders.

  • Many children with complex seizure disorders are on bd doses and higher dosages.

  • The dose may be increased for short periods of 3–5 days with increased seizures, e.g. from viral illness.

  • Elimination half-life of 20–40h means that it may take up to 6 days to reach steady state; there is a risk of accumulation and toxicity with a rapid increase of infusion; consider a loading dose to reach steady state more quickly.

  • Avoid abrupt withdrawal.

  • Associated with salivary hypersecretion and drooling.

  • Tablets may be dispersed in water for administration via an enteral feeding tube.

  • Stability of diluted clonazepam is up to 12h, so prescribers should consider 12-hourly infusions.

  • Compatible with most drugs commonly administered via CSCI via a syringe driver.

  • Available as: tablets (500 micrograms scored, 2mg scored); liquid (0.5mg in 5mL and 2mg in 5mL now available as licensed preparations from Rosemont, but not indicated in children due to high alcohol content; other unlicensed oral liquids are available from specials manufacturers); injection (1mg/mL unlicensed).

Clonidine

Uses

  • Anxiety/sedation (prior to procedure).

  • Pain/sedation/opioid-sparing/prevention of opioid withdrawal effects.

  • Regional nerve block.

  • Spasticity.

  • Behavioural symptoms of irritability, impulsiveness, aggression.

Doses and routes

Anxiety/sedation/pre-procedure

Oral/intranasal/rectal

  • Child >1 month: 4 micrograms/kg as a single dose (suggested maximum 150 micrograms single dose). If used as premedicant prior to a procedure, give 45–60min before.

Pain/sedation/opioid-sparing/prevention of opioid withdrawal effects (most experienced on PICU)

Oral/intravenous bolus

  • Child >1 month: initial dose 1 microgram/kg/dose 3–4 times daily. Increase gradually, as needed and tolerated, to a maximum of 5 micrograms/kg/dose qds.

Intravenous infusion

  • Child >1 month: 0.1–2 micrograms/kg/h.

  • Usual starting doses:

    • child <6 months: 0.4 micrograms/kg/h;

    • child >6 months: 0.6 micrograms/kg/h.

For chronic long-term pain, and once an effective oral dose has been established, consideration can be made to transferring to transdermal patches using a patch size that will give a roughly equivalent daily dose of clonidine (see Formulary Notes below).

Regional nerve block—only in situations where specialist input is available

  • Child >3 months: 1–2 micrograms/kg of clonidine in combination with a local anaesthetic.

Spasticity/movement disorder

Oral

  • Child >1 month: 1–5 micrograms/kg/dose tds. Frequency of dosing may need to be increased and/or alternative route of administration considered if the enteral route is not possible.

Behavioural problems/tics/Tourette’s syndrome

Oral

  • Child >4 years: oral—initial dose of 25 micrograms at night. Increase, as necessary, after 1–2 weeks to 50 micrograms at night. Dose can be further increased by 25 micrograms every 2 weeks to a suggested maximum of 5 micrograms/kg/day or 300 micrograms/day.

Notes

  • Clonidine is a mixed alpha-1 and alpha-2 agonist (mainly alpha-2). Appears to have synergistic analgesic effects with opioids and prevent opioid withdrawal symptoms. Also useful for its sedative effect. Use established in attention-deficit/hyperactivity disorder (ADHD), behavioural problems, and tics.

  • Not licensed for use in children.

  • Licensed indication of clonidine is for the treatment of hypertension, so reduction in blood pressure (BP) is a likely side effect of use. Titrate the dose of clonidine against the symptoms, and monitor BP and pulse on starting treatment and after each dose increase.

  • When used for longer than a few days, clonidine should be withdrawn slowly on discontinuation to prevent acute withdrawal symptoms, including rebound hypertension.

  • Use with caution in those with bradyarrhythmia, Raynaud’s, or other occlusive peripheral vascular disease.

  • Common side effects include constipation, nausea, dry mouth, vomiting, postural hypotension, dizziness, sleep disturbances, headache.

  • Effects of clonidine are abolished by drugs with alpha-2 antagonistic activity, e.g. tricyclics and antipsychotic drugs. Antihypertensive effects may be potentiated by other drugs used to lower BP.

  • Oral bioavailability 75–100%; generally 1:1 conversion iv:oral is suggested as a starting point (largely adult data; note it has been suggested that oral bioavailability may be lower in children).

  • Some reports of use of pr clonidine. Pharmacokinetic studies suggest almost 100% bioavailability via this route. Single pr doses of 2.5–4 micrograms/kg have been used.

  • Onset of effect: oral 30–60min. Time to peak plasma concentration: oral 1.5–5h; epidural 20min; transdermal 2 days.

  • Clonidine has been used successfully by sc injection and infusion—seek specialist advice.

  • Oral solution may be administered via an enteral feeding tube. Alternatively, if the required dose is appropriate to the available tablet strengths, the tablets may be crushed and dispersed in water for administration via an enteral feeding tube. Note: the 25-micrograms tablets do not appear to disperse in water as readily as the 100-micrograms tablets.

  • Chronic conditions—for older children, the use of transdermal patches may be considered when an effective oral dose has been established which is great enough to allow an approximate conversion (1:1) to the transdermal route. Although unlicensed in the UK, three strengths of patches are available, programmed to release 100 micrograms, 200 micrograms, or 300 micrograms of clonidine daily for 7 days.

  • Available as: tablets 25 micrograms, 100 micrograms; injection 150 micrograms/mL; transdermal patch 100 micrograms, 200 micrograms, or 300 micrograms of clonidine daily for 7 days (not licensed in the UK—available via an importation company); and oral solution (special) 50 micrograms/mL.

Co-danthramer (dantron and poloxamer 188)

Uses

  • Constipation in terminal illness only.

Dose and routes

By mouth

Co-danthramer 25/200 suspension 5mL = one co-danthramer 25/200 capsule (dantron 25mg, poloxamer ‘188’ 200mg):

  • child 2–12 years: 2.5–5mL at night;

  • child 6–12 years: one capsule at night;

  • child 12–18 years: 5–10mL or 1–2 capsules at night. Dosage can be increased up to 10–20mL bd.

Strong co-danthramer 75/1000 suspension 5mL = two strong co-danthramer 37.5/500 capsules:

  • child 12–18 years: 5mL or 1–2 capsules at night.

Notes

  • Co-danthramer is made from dantron and poloxamer ‘188’.

  • Acts as a stimulant laxative.

  • Avoid prolonged skin contact due to risk of irritation and excoriation (avoid in urinary or faecal incontinence/children with nappies).

  • Dantron can turn urine red/brown.

  • Rodent studies indicate potential carcinogenic risk.

Co-danthrusate (dantron and docusate sodium)

Uses

  • Constipation in terminal illness only.

Dose and routes

By mouth

Co-danthrusate 50/60 suspension 5mL = one co-danthrusate 50/60 capsule (dantron 50mg/docusate sodium 60mg).

  • Child 6–12 years: 5mL or one capsule at night.

  • Child 12–18 years: 5–15mL or 1–3 capsules at night.

Notes

  • Co-danthrusate is made from dantron and docusate sodium.

  • Acts as a stimulant laxative.

  • Avoid prolonged skin contact due to risk of irritation and excoriation (avoid in urinary or faecal incontinence/children with nappies).

  • Danthron can turn urine red/brown.

  • Rodent studies indicate potential carcinogenic risk.

Codeine phosphate

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has addressed safety concerns with codeine-containing medicines when used for the management of pain in children (June 2013). This follows the PRAC’s review of reports of children who developed serious adverse effects or died after taking codeine for pain relief. Children who are ‘ultrarapid metabolizers’ of codeine are at risk of severe opioid toxicity due to rapid and uncontrolled conversion of codeine into morphine.

The PRAC recommended the following risk minimization measures to ensure that only children for whom benefits are greater than the risks are given the medicine for pain relief:

  • codeine-containing medicines should only be used to treat acute (short-lived) moderate pain in children above 12 years of age, and only if it cannot be relieved by other analgesics such as paracetamol or ibuprofen, because of the risk of respiratory depression associated with codeine use;

  • codeine should not be used at all in children (aged below 18 years) with known obstructive airway disease or those who undergo surgery for the removal of the tonsils or adenoids to treat obstructive sleep apnoea, as these patients are more susceptible to respiratory problems.

(See Formulary http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_ events/news/2013/06/news_detail_001813.jsp&mid= WC0b01ac058004d5c1.)

Further, the WHO now advises there is insufficient evidence to make a recommendation for an alternative to codeine and recommends moving directly from non-opioids (step 1) to low-dose strong opioids for the management of moderate uncontrolled pain in children.

Uses

  • Mild to moderate pain in patients who, through previous use, are known to be able to benefit when other agents are contraindicated or not appropriate. For when required use only—not suitable for management of background pain.

  • Marked diarrhoea, when other agents are contraindicated or not appropriate, with medication doses and interval titrated to effect.

  • Cough suppressant.

Dose and routes

By mouth, rectum, subcutaneous injection, or intramuscular injection

  • Neonate: 0.5–1mg/kg every 4–6h.

  • Child 1 month to 12 years: 0.5–1mg/kg every 4–6h; maximum 240mg daily.

  • Child 12–18 years: 30–60mg every 4–6h; maximum 240mg daily.

As cough suppressant in the form of pholcodine linctus/syrup (NB. different strengths are available)

  • Child 6–12 years: 2.5mg 3–4 times daily.

  • Child 12–18 years: 5–10mg 3–4 times daily.

Notes

  • Not licensed for use in children <1 year old.

  • Codeine is effectively a prodrug for morphine, delivering ~1mg of morphine for every 10mg of codeine.

  • Pharmacologically, codeine is no different from morphine, except that it is weaker and less consistently effective. This has led the WHO to recommend that it is better replaced by low doses of morphine.

  • Conversion to morphine is subject to wide pharmacogenetic variation.

  • 5–34% of population have an enzyme deficiency that prevents activation of codeine to the active metabolite, and so it is ineffective in this group.

  • Individuals who are ultrarapid metabolizers can develop life-threatening opioid toxicity.

  • Seems relatively constipating, compared with morphine/diamorphine, particularly in children.

  • Rectal administration is an unlicensed route of administration using an unlicensed product.

  • Must not be given iv.

  • Reduce dose in renal impairment.

  • Available as: tablets (15mg, 30mg, 60mg), oral solution (25mg/5mL), injection (60mg/mL), and suppositories of various strengths available from ‘specials’ manufacturers. Pholcodine as linctus 2mg/5mL, 5mg/5mL, and 10mg/5mL.

  • Some community pharmacies do not stock codeine phosphate solution at 25mg/5mL. They usually do stock codeine phosphate linctus at 15mg/5mL, and this is worth enquiring of if a practitioner is working in the community and wishes to prescribe this medication. BE CAREFUL WITH DIFFERING STRENGTHS OF LIQUIDS.

Cyclizine

Uses

  • Antiemetic of choice for raised intracranial pressure.

  • Nausea and vomiting where other more specific antiemetics (metoclopramide, 5HT3 antagonists) have failed.

Dose and routes

By mouth or by slow intravenous injection over 3–5min

  • Child 1 month to 6 years: 0.5–1mg/kg up to tds; maximum single dose 25mg.

  • Child 6–12 years: 25mg up to tds.

  • Child 12–18 years: 50mg up to tds.

By rectum

  • Child 2–6 years: 12.5mg up to tds.

  • Child 6–12 years: 25mg up to tds.

  • Child 12–18 years: 50mg up to tds.

By continuous intravenous or subcutaneous infusion

  • Child 1 month to 5 years: 3mg/kg over 24h (maximum 50mg/24h).

  • Child 6–12 years: 75mg over 24h.

  • Child 12–18 years: 150mg over 24h.

Notes

  • Antihistaminic, antimuscarinic, antiemetic.

  • Tablets are not licensed for use in children <6 years old.

  • Injection is not licensed for use in children.

  • Antimuscarinic side effects include dry mouth, drowsiness, headache, fatigue, dizziness, thickening of bronchial secretions, and nervousness.

  • Rapid sc or iv bolus can lead to ‘light-headedness’—disliked by some and enthralling to others, leading to repeated quests for iv cyclizine.

  • Care with sc or iv infusion—acidic pH and can cause injection site reactions.

  • For CSCI or iv infusion, dilute only with water for injection (WFI) or 5% glucose; incompatible with 0.9% saline and will precipitate.

  • Concentration-dependent incompatibility with alfentanil, dexamethasone, diamorphine, and oxycodone.

  • Suppositories must be kept refrigerated.

  • Tablets may be crushed for oral administration. The tablets do not disperse well in water, but, if shaken in 10mL of water for 5min, the resulting dispersion may be administered immediately via an enteral feeding tube.

  • Available as: tablets (50mg), suppositories (12.5mg, 25mg, 50mg, 100mg from ‘specials’ manufacturers), and injection (50mg/mL).

Dantrolene

Uses

  • Skeletal muscle relaxant.

  • Chronic severe muscle spasm or spasticity.

Dose and routes

The dose of dantrolene should be built up slowly.

By mouth

  • Child 5–12 years: initial dose of 500 micrograms/kg once daily (od); after 7 days, increase to 500 micrograms/kg/dose tds. Every 7 days, increase by a further 500 micrograms/kg/dose until response. Maximum recommended dose is 2mg/kg 3–4 times daily (maximum total daily dose 400mg).

  • Child 12–18 years: initial dose of 25mg od; after 7 days, increase to 25mg tds. Every 7 days, increase by a further 500 micrograms/kg/dose until response. Maximum recommended dose is 2mg/kg 3–4 times daily (maximum total daily dose 400mg).

Notes

  • Not licensed for use in children.

  • Hepatotoxicity risk; consider checking liver function before, and at regular intervals during, therapy. Contraindicated in hepatic impairment—avoid in liver disease or concomitant use of hepatotoxic drugs.

  • Can cause drowsiness, dizziness, weakness, and diarrhoea.

  • Available as: capsules (25mg, 100mg) and oral suspension (extemporaneous formulation).

Dexamethasone

Uses

  • Headache associated with raised intracranial pressure caused by a tumour.

  • Anti-inflammatory in the brain and other tumours causing pressure on nerves or bone, or obstruction of hollow viscus.

  • Analgesic role in nerve compression, spinal cord compression, and bone pain.

  • Antiemetic either as an adjuvant or in highly emetogenic cytotoxic therapies.

Dose and routes

Prescribe as a dexamethasone base.

Headache associated with raised intracranial pressure

By mouth or intravenously

  • Child 1 month to 12 years: 250 micrograms/kg bd for 5 days; then reduce or stop.

To relieve symptoms of brain or other tumour

Numerous other indications in cancer management, such as spinal cord and/or nerve compression, some causes of dyspnoea, bone pain, SVC obstruction, etc.; only in discussion with the specialist palliative medicine team. High doses <16mg/24h may be advised.

Antiemetic

By mouth or intravenously

  • Child <1 year: initial dose 250 micrograms tds. This dose may be increased, as necessary and as tolerated, up to 1mg tds.

  • Child 1–5 years: initial dose 1mg tds. This dose may be increased, as necessary and as tolerated, up to 2mg tds.

  • Child 6–12 years: initial dose 2mg tds. This dose may be increased, as necessary and as tolerated, up to 4mg tds.

  • Child 12–18 years: 4mg tds.

Notes

  • Not licensed for use in children as an antiemetic.

  • Dexamethasone has high glucocorticoid activity, but insignificant mineralocorticoid activity, so is particularly suited for high-dose anti-inflammatory therapy.

  • Dexamethasone can be given in a single daily dose each morning for most indications; this reduces the likelihood of corticosteroid-induced insomnia and agitation.

  • Dexamethasone has an oral bioavailability of >80%; it can be converted to sc or iv on a 1:1 basis.

  • Dexamethasone 1mg = dexamethasone phosphate 1.2mg = dexamethasone sodium phosphate 1.3mg.

  • Dexamethasone 1mg = 7mg prednisolone (anti-inflammatory equivalence).

  • Dexamethasone has a long duration of action.

  • Problems of weight gain and Cushingoid appearance are major problems specifically in children. All specialist units therefore use pulsed-dose regimes, in preference to continual use. Regimes vary with conditions and specialist units. Seek local specialist advice.

  • Other side effects include: diabetes, osteoporosis, muscle wasting, peptic ulceration, and behavioural problems, particularly agitation.

  • Dexamethasone can be stopped abruptly if given for a short duration of time (<7 days); otherwise gradual withdrawal is advised.

  • Tablets may be dispersed in water if oral liquid unavailable. Oral solution or tablets dispersed in water may be administered via an enteral feeding tube.

  • Available as: tablets (500 micrograms, 2mg), oral solution (2mg/5mL and other strengths available from ‘specials’ manufacturers), and injection as dexamethasone sodium phosphate (equivalent to 4mg/1mL dexamethasone base (Organon® brand) or 3.3mg/mL dexamethasone base (Hospira® brand)).

Diamorphine

Uses

  • Moderate to severe pain.

  • Dyspnoea.

Dose and routes

Normally convert using OME from previous analgesia.

Use the following starting doses in opioid-naïve patients. The maximum dose stated applies to the starting dose only.

Acute or chronic pain

By continuous subcutaneous or intravenous infusion

  • Neonate: initial dose of 2.5 micrograms/kg/h which can be increased, as necessary, to a suggested maximum of 7 micrograms/kg/h.

  • Child 1 month to 18 years: 7–25 micrograms/kg/h (initial maximum 10mg/24h), adjusted according to response.

By intravenous, subcutaneous, or intramuscular injection

  • Neonate: 15 micrograms/kg every 6h, as necessary, adjusted according to response.

  • Child 1–3 months: 20 micrograms/kg every 6h, as necessary, adjusted according to response.

  • Child 3–6 months: 25–50 micrograms/kg every 6h, as necessary, adjusted according to response.

  • Child 6–12 months: 75 micrograms/kg every 4h, as necessary, adjusted according to response.

  • Child 1–12 years: 75–100 micrograms/kg every 4h, as necessary, adjusted according to response. Suggested initial maximum dose of 2.5mg.

  • Child 12–18 years: 75–100 micrograms/kg every 4h, as necessary, adjusted according to response. Suggested initial maximum dose of 2.5–5mg.

By intranasal or buccal route

  • Child over 10kg: 50–100 micrograms/kg; maximum single dose 10mg.

Injection solution can be used by intranasal or buccal routes or a nasal spray (Ayendi®) now available and licensed for use in children aged 2 years and over (weight 12kg upwards) for the management of severe acute pain.

720 micrograms/actuation

  • 12–18kg: two sprays as a single dose.

  • 18–24kg: three sprays as a single dose.

  • 24–30kg: four sprays as a single dose.

1600 micrograms/actuation

  • 30–40kg: two sprays as a single dose.

  • 40–50kg: three sprays as a single dose.

Breakthrough

By buccal, subcutaneous, or intravenous routes

  • For breakthrough pain, use 5–10% of total daily diamorphine dose every 1–4h, as needed.

Dyspnoea

By buccal, subcutaneous, or intravenous routes

  • Dose as for pain, but at 50% of breakthrough dose.

Notes

  • Diamorphine injection is licensed for the treatment of children who are terminally ill.

  • For intranasal or buccal administration of diamorphine, use the injection powder reconstituted in WFIs (unlicensed route of administration), or the nasal spray may be used (licensed for use in the management of severe acute pain from 2 years of age).

  • In neonates, the dosage interval should be extended to 6- or 8-hourly, depending on renal function, and the dose carefully checked, due to increased sensitivity to opioids in the first year of life.

  • In poor renal function, the dosage interval may be lengthened, or opioids only given as required and titrated against symptoms. Consider changing to fentanyl.

  • For CSCI, dilute with WFIs, as concentration incompatibility occurs with 0.9% saline at above 40mg/mL.

  • Diamorphine can be given by sc infusion up to a strength of 250mg/mL.

  • Morphine injection is rapidly taking over from diamorphine, as the only benefit of diamorphine over morphine is its better solubility when high doses are needed, and this is rarely a problem in paediatric doses.

  • Available as: injection (5mg, 10mg, 30mg, 100mg, 500mg ampoules) and nasal spray 720 micrograms/actuation and 1600 micrograms/actuation (Ayendi® nasal spray).

Diazepam

Uses

  • Short-term anxiety relief.

  • Agitation.

  • Panic attacks.

  • Relief of muscle spasm.

  • Treatment of status epilepticus.

Dose and routes

Short-term anxiety relief, panic attacks, and agitation

By mouth

  • Child 2–12 years: 1–2mg tds.

  • Child 12–18 years: initial dose of 2mg tds, increasing, as necessary and as tolerated, to a maximum of 10mg tds.

Relief of muscle spasm

By mouth

  • Child 1–12 months: initial dose of 250 micrograms/kg bd.

  • Child 1–5 years: initial dose of 2.5mg bd.

  • Child 5–12 years: initial dose of 5mg bd.

  • Child 12–18 years: initial dose of 10mg bd; maximum total daily dose 40mg.

Status epilepticus

By intravenous injection over 3–5min

  • Neonate: 300–400 micrograms/kg as a single dose, repeated once after 10min, if necessary.

  • Child 1 month to 12 years: 300–400 micrograms/kg (maximum 10mg), repeated once after 10min, if necessary.

  • Child 12–18 years: 10mg, repeated once after 10min, if necessary (in hospital, up to 20mg as a single dose may be used).

By rectum (rectal solution)

  • Neonate: 1.25–2.5mg, repeated once after 10min, if necessary.

  • Child 1 month to 2 years: 5mg, repeated once after 10min, if necessary.

  • Child 2–12 years: 5–10mg, repeated once after 10min, if necessary,

  • Child 12–18 years: 10mg, repeated once after 10min, if necessary (in hospital, up to 20mg as a single dose may be used).

Notes

  • Do not use in acute or severe respiratory insufficiency, unless in the imminently dying.

  • Rectal tubes not licensed for children <1 year old.

  • Use with caution in mild to moderate hepatic disease.

  • Metabolized via the cytochrome P450 group of liver enzymes—potential for interaction with any concurrent medicine that induces or inhibits this group of enzymes. Enhancement of the central depressive effect may occur if diazepam is combined with drugs such as neuroleptics, antipsychotics, tranquillizers, antidepressants, hypnotics, analgesics, anaesthetics, barbiturates, and sedative antihistamines.

  • Can cause dose-dependent drowsiness and impaired psychomotor and cognitive skills.

  • Almost 100% bioavailable when given po or by rectal solution.

  • Onset of action ~15min given po and within 1–5min given iv. Given as rectal solution, diazepam is rapidly absorbed from the rectal mucosa, with maximum serum concentration reached within 17min.

  • Long plasma half-life of 24–48h, with the active metabolite nordiazepam having a plasma half-life of 48–120h.

  • The oral solution may be administered via a gastrostomy tube. For administration via a jejunostomy tube, consider using tablets dispersed in water to reduce osmolarity.

  • Available as: tablets (2mg, 5mg, 10mg), oral solution (2mg/5mL, 5mg/5mL), rectal tubes (2.5mg, 5mg, 10mg), and injection (5mg/mL solution and 5mg/mL emulsion).

Diclofenac sodium

Uses

  • Mild to moderate pain and inflammation, particularly musculoskeletal disorders.

Dose and routes

By mouth or rectum

  • Child 6 months to 18 years: initial dose of 0.3mg/kg tds, increasing, if necessary, to a maximum of 1mg/kg tds (maximum 50mg single dose).

By intramuscular or intravenous infusion

  • Child 2–18 years: initial dose of 0.3mg/kg 1–2 times daily; maximum of 150mg/day and for a maximum of 2 days.

Notes

Will cause closure of ductus arteriosus; contraindicated in duct-dependent congenital heart disease.

  • Not licensed for use in children under 1 year; suppositories not licensed for use in children under 6 years, except for use in children over 1 year for juvenile idiopathic arthritis; solid dose forms containing >25mg not licensed for use in children; injection (for im bolus or iv infusion only) not licensed for use in children.

  • The risk of cardiovascular events secondary to NSAID use is undetermined in children. In adults, all NSAID use (including COX-2 selective inhibitors) can, to varying degrees, be associated with a small increased risk of thrombotic events (e.g. myocardial infarction and stroke), independent of baseline cardiovascular risk factors or duration of NSAID use; however, the greatest risk may be in those patients receiving high doses long-term. A small increased thrombotic risk cannot be excluded in children.

  • All NSAIDs are associated with gastrointestinal toxicity. In adults, evidence on the relative safety of NSAIDs indicates differences in the risks of serious upper gastrointestinal side effects—piroxicam and ketorolac are associated with the highest risk; indometacin, diclofenac, and naproxen are associated with intermediate risk, and ibuprofen with the lowest risk (although high doses of ibuprofen have been associated with intermediate risk).

  • The smallest dose that can be given practically by the rectal route is 3.125mg by cutting a 12.5mg suppository into quarters (CC).

  • For iv infusion, dilute in 5% glucose or 0.9% NaCl, and infuse over 30–120min.

  • Dispersible tablets may be administered via an enteral feeding tube. Disperse immediately before administration.

  • Available as: tablets (25mg, 50mg, and 75mg modified-release), dispersible tablets (10mg from a ‘specials’ manufacturer, 50mg), modified-release capsules (75mg and 100mg), injection (25mg/mL Voltarol® for im injection or iv infusion only), and suppositories (12.5mg, 25mg, 50mg, and 100mg).

Dihydrocodeine

Uses

  • Mild to moderate pain in patients known to be able to benefit.

Dose and routes

By mouth or deep subcutaneous or intramuscular injection

  • Child 1–4 years: 500 micrograms/kg every 4–6h.

  • Child 4–12 years: initial dose of 500 micrograms/kg (maximum 30mg/dose) every 4–6h. Dose may be increased, if necessary, to 1mg/kg every 4–6h (maximum 30mg/dose).

  • Child 12–18 years: 30mg (maximum 50mg by im or deep sc injection) every 4–6h.

  • Modified-release tablets used 12-hourly (use half of previous total daily dose for each modified-release dose).

Notes

  • Most preparations not licensed for children under 4 years.

  • Relatively constipating, compared with morphine/diamorphine, and has a ceiling analgesic effect.

  • Dihydrocodeine is itself an active substance, not a prodrug like codeine.

  • Oral bioavailability 20%, so probably equipotent with codeine by mouth (but opinion varies), twice as potent as codeine by injection.

  • Time to onset 30min; duration of action 4h for immediate-release tablets.

  • Side effects as for other opioids, plus paralytic ileus, abdominal pain, and paraesthesiae.

  • Precautions: avoid or reduce dose in hepatic or renal failure.

  • Available as: tablets (30mg, 40mg), oral solution (10mg/5mL), injection (CD) (50mg/mL 1mL ampoules), and modified-release tablets (60mg, 90mg, 120mg).

Docusate

Uses

  • Constipation (faecal softener).

Dose and routes

By mouth

  • Child 6 months to 2 years: initial dose of 12.5mg tds; adjust dose, according to response.

  • Child 2–12 years: initial dose of 12.5mg tds. Increase to 25mg tds, as necessary, and then further adjust dose, according to response.

  • Child 12–18 years: initial dose 100mg/dose tds. Adjust as needed, according to response, up to 500mg/day in divided doses.

By rectum

  • Child 12–18 years: one enema as a single dose.

Notes

  • Adult oral solution and capsules not licensed in children <12 years.

  • Oral preparations act within 1–2 days.

  • Rectal preparations act within 20min.

  • Mechanism of action is emulsifying, wetting, and mild stimulant.

  • Doses may be exceeded on specialist advice.

  • Available as: capsules (100mg), oral solution (12.5mg/5mL paediatric, 50mg/5mL adult), and enema (120mg in 10g single-dose pack).

Domperidone

Medicines and Healthcare products Regulatory Agency (MHRA), April 2014: domperidone is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of symptoms of nausea and vomiting, and the dosage and duration of use have been reduced. Domperidone is now contraindicated for use in those with underlying cardiac conditions and other risk factors.

The indications and doses below are therefore largely unlicensed usage in a particular population. Use the minimum effective dose. Do not use in those with known cardiac problems or other risk factors.

Uses

  • Nausea and vomiting where poor gastrointestinal motility is the cause.

  • Gastro-oesophageal reflux resistant to other therapy.

Dose and routes

For nausea and vomiting

By mouth

  • >1 month and body weight ≤35kg: initial dose of 250 micrograms/kg 3–4 times daily, increasing, if necessary, to 500 micrograms/kg 3–4 times daily. Maximum 2.4mg/kg (or 80mg) in 24h.

  • Body weight >35kg: initial dose of 10mg 3–4 times daily, increasing, if necessary, to 20mg 3–4 times daily. Maximum 80mg in 24h.

By rectum

  • Body weight 15–35kg: 30mg bd.

  • Body weight >35kg: 60mg bd.

For gastro-oesophageal reflux and gastrointestinal stasis

By mouth

  • Neonate: initial dose of 100 micrograms/kg 4–6 times daily before feeds. Dose may be increased, if necessary, to maximum of 300 micrograms/kg 4–6 times daily.

  • Child 1 month to 12 years: initial dose of 200 micrograms/kg (maximum single dose 10mg) 3–4 times daily before food. Dose may be increased, if necessary, to 400 micrograms/kg 3–4 times daily. Maximum single dose 20mg.

  • Child 12–18 years: initial dose of 10mg 3–4 times daily before food. Dose may be increased, if necessary, to 20mg 3–4 times daily.

Notes

  • Domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death.

  • Domperidone is contraindicated in those:

    • with conditions where cardiac conduction is, or could be, impaired;

    • with underlying cardiac diseases such as congestive heart failure;

    • receiving other medications known to prolong the QT interval (e.g. erythromycin, ketoconazole) or which are potent CYP3A4 inhibitors;

    • with severe hepatic impairment.

  • This risk may be higher with daily doses >30mg. Use at the lowest effective dose.

  • Not licensed for use in gastrointestinal stasis; not licensed for use in children for GORD.

  • Reduced ability to cross the blood–brain barrier, so less likely to cause extrapyramidal side effects, compared with metoclopramide.

  • Promotes gastrointestinal motility, so diarrhoea can be an unwanted (or useful) side effect.

  • Not to be used in patients with hepatic impairment.

  • For administration via an enteral feeding tube—use the suspension formulation, although the total daily dose of sorbitol should be considered. If administering into the jejunum, dilute the suspension with at least an equal volume of water immediately prior to administration.

  • Available as: tablets (10mg), oral suspension (5mg/5mL), and suppositories (30mg).

Entonox® (nitrous oxide)

Uses

  • As self-regulated analgesia, without loss of consciousness.

  • Particularly useful for painful dressing changes.

Dose and routes

By inhalation

  • Child usually >5 years old: self-administration using a demand valve. Up to 50% in oxygen, according to the child’s needs.

Notes

  • Is normally used as a light anaesthesic.

  • Rapid onset and then offset.

  • Should only be used as self-administration, using a demand valve; all other situations require a specialist paediatric anaesthetist.

  • Use is dangerous in the presence of pneumothorax or intracranial air after head injury.

  • Prolonged use can cause megaloblastic anaemia.

  • May be difficult to make available in hospice settings, especially if needed infrequently, due to training, governance, and supply implications.

Erythromycin

Uses

  • Gastrointestinal stasis (motilin receptor agonist).

Dose and routes

By mouth

  • Neonate: 3mg/kg qds.

  • Child 1 month to 18 years: 3mg/kg qds.

Notes

  • Not licensed for use in children with gastrointestinal stasis.

  • Erythromycin is excreted principally by the liver, so caution should be exercised in administering the antibiotic to patients with impaired hepatic function or concomitantly receiving potentially hepatotoxic agents.

  • Erythromycin is a known inhibitor of the cytochrome P450 system and may increase the serum concentration of drugs which are metabolized by this system. Appropriate monitoring should be undertaken, and dosage should be adjusted, as necessary. Particular care should be taken with medications known to prolong the QT interval of the electrocardiogram (ECG).

  • Available as: tablets (250mg, 500mg) and oral suspension (125mg/5mL, 250mg/5mL, 500mg/5mL).

Etamsylate

Uses

  • Treatment of haemorrhage, including surface bleeding from ulcerating tumours.

Dose and routes

By mouth

  • >18 years: 500mg qds, indefinitely or until a week after cessation of bleeding.

Notes

  • Not licensed for use in children with haemorrhage.

  • Available as: tablets (500mg).

Etoricoxib

Uses

  • Anti-inflammatory analgesic; adjuvant for musculoskeletal pain.

Dose and routes

Oral

  • Child 12–16 years: initial dose of 30mg od. Dose may be increased, as necessary and as tolerated, to a maximum of 60mg od.

  • Child 16 years and older: usual dose of 30–90mg od. Doses up to 120mg have been used on a short-term basis in acute gouty arthritis in adults.

Notes

  • Oral selective COX-2 inhibitor.

  • Etoricoxib is not licensed for use in children <16 years of age. The pharmacokinetics of etoricoxib in children <12 years of age have not been studied.

  • Etoricoxib may mask fever and other signs of inflammation.

  • All NSAIDs should be used with caution in children with a history of hypersensitivity to any NSAID or in those with a coagulation disorder.

  • Etoricoxib is contraindicated in those with: active peptic ulceration or active gastrointestinal bleeding, severe hepatic or renal dysfunction, inflammatory bowel disease, or congestive heart failure.

  • The risk of cardiovascular events secondary to NSAID use is undetermined in children. In adults, COX-2 selective inhibitors, diclofenac (150mg daily), and ibuprofen (2.4g daily) are associated with an increased risk of thrombotic effects (e.g. myocardial infarction and stroke).

  • All NSAIDs are associated with gastrointestinal toxicity. In adults, evidence on the relative safety of NSAIDs indicates differences in the risks of serious upper gastrointestinal side effects, with piroxicam and ketorolac associated with the highest risk, and ibuprofen at low to medium dose with the lowest risk. Selective COX-2 inhibitors are associated with a lower risk of serious upper gastrointestinal side effects than non-selective NSAIDs. Children appear to tolerate NSAIDs better than adults, and gastrointestinal side effects are less common, although they do still occur.

  • Common (1–10% of patients) adverse events: alveolar osteitis; oedema/fluid retention; dizziness, headache; palpitations, arrhythmia; hypertension; bronchospasm; abdominal pain; constipation, flatulence, gastritis, heartburn/acid reflux, diarrhoea, dyspepsia/epigastric discomfort, nausea, vomiting, oesophagitis, oral ulcer; alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased; ecchymosis; asthenia/fatigue, flu-like disease.

  • Potential drug interactions include warfarin (increase in international normalized ratio (INR)), and diuretics, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II antagonists (increased risk of compromised renal function). Etoricoxib does NOT appear to inhibit or induce CYP isoenzymes. However, the main pathway of etoricoxib metabolism is dependent on CYP enzymes (primarily CYP3A4), so co-administration with drugs that are inducers or inhibitors of this pathway may affect the metabolism of etoricoxib.

  • Etoricoxib is administered po and may be taken with or without food. However, the onset of effect may be faster when administered without food.

  • Etoricoxib tablets may be dispersed in 10mL of water and will disintegrate to give fine granules that settle quickly but disperse easily and flush down an 8Fr NG or gastrostomy tube without blockage.

  • Available as: film-coated tablets (30mg, 60mg, 90mg, 120mg). Tablets contain lactose.

Fentanyl

Uses

  • Step 2 WHO pain ladder, once dose is titrated.

Dose and routes

Normally convert using OME from previous analgesia.

Use the following starting doses in the opioid-naïve patient. The maximum dose stated applies to the starting dose only.

By transmucosal application (lozenge with oromucosal applicator)

  • Child 2–18 years and >10kg: 15 micrograms/kg as a single dose, titrated to a maximum dose of 400 micrograms (higher doses under specialist supervision).

By intranasal

  • Neonate to child <2 years: 1 microgram/kg as a single dose.

  • Child 2–18 years: 1–2 micrograms/kg as a single dose, with an initial maximum single dose of 50 micrograms.

By transdermal patch or continuous infusion

  • Based on oral morphine dose equivalent (given as 24h totals).

By intravenous injection

  • Neonate or infant: 1–2 micrograms/kg per dose slowly over 3–5min; repeated every 2–4h.

  • Child: 1–2 micrograms/kg per dose; repeated every 30–60min.

By continuous intravenous infusion

  • Neonate or infant: initial iv bolus of 1–2 micrograms/kg (slowly over 3–5min), followed by 0.5–1 micrograms/kg/h.

  • Child: initial iv bolus of 1–2 micrograms/kg (slowly over 3–5min), followed by 0.5–1 micrograms/kg/h.

The 72h fentanyl patches are approximately equivalent to the following 24h doses of oral morphine.

Morphine salt 30mg daily

fentanyl ‘12’ patch

Morphine salt 60mg daily

fentanyl ‘25’ patch

Morphine salt 120mg daily

fentanyl ‘50’ patch

Morphine salt 180mg daily

fentanyl ‘75’ patch

Morphine salt 240mg daily

fentanyl ‘100’ patch

Notes

  • Fentanyl patches should be changed every 72h, and the site of application rotated.

  • Injection not licensed for use in children <2 years of age. Lozenges and nasal sprays are not licensed for use in children.

  • The injection solution can be administered by the intranasal route for doses <50 micrograms which is the lowest strength of nasal spray available.

  • Injection solution could be administered drop-wise (may be unpleasant) or using an atomizer device that Accident and Emergency units use for intranasal diamorphine.

  • The main advantage of fentanyl over morphine in children is its availability as a transdermal formulation.

  • It can simplify analgesic management in patients with poor, deteriorating, or even absent renal function.

  • Avoid or reduce dose in hepatic impairment.

  • It is a synthetic opioid, very different in structure from morphine, and therefore ideal for opioid switching.

  • Evidence that it is less constipating than morphine has not been confirmed in more recent studies.

  • The patch formulation is not usually suitable for the initiation or titration phases of opioid management in palliative care, since the patches represent large increments and because of the time lag to achieve steady state.

  • The usefulness of lozenges in children is limited by the dose availability and no reliable conversion factor which also varies between preparations. Another caution is that opioid morphine approximate equivalence of the smallest lozenge (200 micrograms) is 30mg, meaning it is probably suitable to treat breakthrough pain only for children receiving a total daily dose equivalent of 180mg morphine or more. Older children will often choose to remove the lozenge before it is completely dissolved, giving them some much valued control over their analgesia. NB. The lozenge must be rotated in the buccal pouch, and not sucked. Unsuitable for pain in advanced neuromuscular disorders where independent physical rotation of the lozenge is not possible.

  • Pharmacokinetics of fentanyl intranasally are favourable, but it is not always practical and/or well tolerated in children.

Available as fentanyl citrate:

  • intranasal spray (50 micrograms/metered spray, 100 micrograms/metered spray, 200 micrograms/metered spray Instanyl®). Also available as PecFent® 100 micrograms/metered spray and 400 micrograms/metered spray;

  • lozenge with oromucosal applicator (200 micrograms, 400 micrograms, 600 micrograms, 800 micrograms, 1.2mg, 1.6mg Actiq®);

  • sublingual tablets (100, 200, 300, 400, 600, and 800 micrograms Abstral® ) and buccal tablets (Effentora® 100, 200, 400, 600, and 800 micrograms; Breakyl® 200, 400, 600, 800, and 1200 micrograms);

  • patches (12 micrograms/h, 25 micrograms/h, 50 micrograms/h, 75 micrograms/h, 100 micrograms/h).

Fluconazole

Uses

  • Mucosal candidiasis infection, invasive candidal infections, or prevention of fungal infections in immunocompromised patients.

Dose and routes

Mucosal candidal infection

By mouth or intravenous infusion

  • Neonate under 2 weeks: 3–6mg/kg on the first day, then 3mg/kg every 72h.

  • Neonate between 2 and 4 weeks: 3–6mg/kg on the first day, then 3mg/kg every 48h.

  • Child 1 month to 12 years: 3–6mg/kg on the first day, then 3mg/kg (maximum 100mg) daily.

  • Child 12–18 years: 50mg/day. Increase to 100mg/day in difficult infections.

Invasive candidal and cryptococcal infections

By mouth or intravenous infusion

  • Neonate under 2 weeks: 6–12mg/kg every 72h.

  • Neonate over 2 weeks: 6–12mg/kg every 48h.

  • Child 1 month to 18 years: 6–12mg/kg (maximum 800mg) every 24h.

Prevention of fungal infections in immunocompromised patients

By mouth or intravenous infusion

  • Neonate under 2 weeks: 3–12mg/kg every 72h.

  • Neonate over 2 weeks: 3–12mg/kg every 48h.

  • Child 1 month to 18 years: 3–12mg/kg (maximum 400mg) every 24h.

Notes

  • Use for 7–14 days in oropharyngeal candidiasis.

  • Use for 14–30 days in other mucosal infections.

  • Different duration of use in severely immunocompromised patients.

  • Fluconazole is a potent CYP2C9 inhibitor and a moderate CYP3A4 inhibitor. Fluconazole is also an inhibitor of CYP2C19. Fluconazole-treated patients who are concomitantly treated with medicinal products with a narrow therapeutic window metabolized through CYP2C9, CYP2C19, and CYP3A4 should be monitored.

  • The most frequently (>1 in 10) reported adverse reactions are headache, abdominal pain, diarrhoea, nausea, vomiting, ALT increase, AST increase, blood alkaline phosphatase increase, and rash.

  • For iv infusion, give over 10–30min; do not exceed an infusion rate of 5–10mL/min.

  • Oral suspension may be administered via an enteral feeding tube.

  • Available as: capsules (50mg, 150mg, 200mg), oral suspension (50mg/5mL, 200mg/mL), and iv infusion (2mg/mL in 2mL, 50mL or 100mL infusion bags).

Fluoxetine

Uses

  • Major depression.

Dose and routes

By mouth

  • Child 8–18 years: initial dose 10mg od. May increase after 1–2 weeks, if necessary, to a maximum of 20mg od.

Notes

  • Licensed for use in children from 8 years of age.

  • Use with caution in children, ideally with specialist psychiatric advice.

  • Increased risk of anxiety for the first 2 weeks.

  • Onset of benefit 3–4 weeks.

  • Consider long half-life when adjusting dosage. Do not discontinue abruptly.

  • May also help for neuropathic pain and intractable cough.

  • Suicide-related behaviours have been more frequently observed in clinical trials amongst children and adolescents treated with antidepressants, compared with placebo. Mania and hypomania have been commonly reported in paediatric trials.

  • The most commonly reported adverse reactions in patients treated with fluoxetine were headache, nausea, insomnia, fatigue, and diarrhoea. Undesirable effects may decrease in intensity and frequency with continued treatment and do not generally lead to cessation of therapy.

  • Because the metabolism of fluoxetine (like tricyclic antidepressants and other selective serotonin antidepressants) involves the hepatic cytochrome CYP2D6 isoenzyme system, concomitant therapy with drugs also metabolized by this enzyme system may lead to drug interactions.

  • Must not be used in combination with a MAOI.

  • Available as: capsules (20mg) and oral liquid (20mg/5mL).

Gabapentin

Uses

  • Adjuvant in neuropathic pain.

Dose and routes

By mouth

Child >2 years

  • Day 1: 10mg/kg as a single dose (maximum single dose 300mg).

  • Day 2: 10mg/kg bd (maximum single dose 300mg).

  • Day 3 onwards: 10mg/kg tds (maximum single dose 300mg).

  • Increase further, if necessary, to maximum of 20mg/kg/dose (maximum single dose 600mg).

From 12 years

  • The maximum daily dose can be increased, according to response, to a maximum of 3600mg/day.

Notes

  • Not licensed for use in children with neuropathic pain.

  • Speed of titration after the first 3 days varies between increases every 3 days for fast regime to increases every 1–2 weeks in debilitated children or when on other CNS depressants.

  • No consensus on dose for neuropathic pain. Doses given, based on doses for partial seizures and authors’ experience.

  • Dose reduction required in renal impairment. Consult the manufacturer’s literature.

  • Very common (>1 in 10) side effects: somnolence, dizziness, ataxia, viral infection, fatigue, fever.

  • Capsules can be opened but have a bitter taste.

  • Available as: capsules (100mg, 300mg, 400mg), tablets (600mg, 800mg), and oral solution 50mg in 5mL (Rosemont—however, this product contains propylene glycol, acesulfame K, and saccharin sodium, and levels may exceed the recommended WHO daily intake limits if high doses are given to adolescents with low body weight (39–50kg)).

Gaviscon®

Uses

  • Gastro-oesophageal reflux, dyspepsia, and heartburn.

Dose and routes

By mouth

  • Neonate to 2 years, body weight <4.5kg: one dose (half dual sachet) when required, mixed with feeds or with water for breastfed babies; maximum six doses in 24h.

  • Neonate to 2 years body weight >4.5kg: two doses (one dual sachet) when required, mixed with feeds or with water for breastfed babies or older infants; maximum six doses in 24h.

Gaviscon®

  • Child 2–12 years: one tablet or 5–10mL of liquid after meals and at bedtime.

  • Child 12–18 years: 1–2 tablets or 10–20mL after meals and at bedtime.

Gaviscon® Advance

  • Child 2–12 years: one tablet or 2.5–5mL after meals and at bedtime (under medical advice only).

  • Child 12–18 years: 1–2 tablets or 5–10mL suspension after meals and at bedtime.

Notes

  • Gaviscon Infant® sachets licensed for infants and young children up to 2 years of age, but use in <1 year only under medical supervision. Gaviscon® liquid and tablets—licensed for use from 2 years of age, but age 2–6 years only on medical advice. Gaviscon® Advance suspension and tablets licensed for use from 12 years of age; under 12 years on medical advice only.

  • Gaviscon Infant® should not be used with feed thickeners nor with excessive fluid losses (e.g. fever, diarrhoea, vomiting).

  • Gaviscon® liquid contains 3.1mmol of sodium per 5mL; Gaviscon® tablets contain 2.65mmol of sodium and also contain aspartame. Gaviscon® Advance suspension contains 2.3mmol of sodium and 1mmol of potassium per 5mL and 2.25mmol of sodium and 1mmol of potassium per 5mL and also contain aspartame. Gaviscon Infant® sachets contain 0.92mmol of sodium per dose (half dual sachet).

  • Available as: Gaviscon® liquid and tablets, Gaviscon® Advance suspension and tablets, and infant sachets (come as dual sachets; each half of a dual sachet is considered one dose).

Glycerin (glycerol)

Uses

  • Constipation.

Dose and routes

By rectum

  • Neonate: tip of a glycerin suppository (slice a small chip of a 1g suppository with a blade).

  • Child 1 month to 1 year: 1g infant suppository, as required.

  • Child 1–12 years: 2g child suppository, as required.

  • Child 12–18 years: 4g adult suppository, as required.

Notes

  • Moisten with water before insertion.

  • Hygroscopic and lubricant actions. May also be a rectal stimulant.

  • Response usually in 20min to 3h.

  • Available as: suppositories (1g, 2g, and 4g).

Glycopyrronium bromide

Uses

  • Control of upper airways secretion and hypersalivation.

Dose and routes

By mouth

  • Child 1 month to 18 years: initial dose of 40 micrograms/kg 3–4 times daily. The dose may be increased, as necessary, to 100 micrograms/kg 3–4 times daily. Maximum 2mg/dose given tds.

Subcutaneous

  • Child 1 month to 12 years: initial dose of 4 micrograms/kg 3–4 times daily. The dose may be increased, as necessary, to 10 micrograms/kg 3–4 times daily. Maximum 200 micrograms/dose given qds.

  • Child 12–18 years: 200 micrograms every 4h when required.

Continuous subcutaneous infusion

  • Child 1 month to 12 years: initial dose of 10 micrograms/kg/24h. The dose may be increased, as necessary, to 40 micrograms/kg/24h (maximum 1.2mg/24h).

  • Child 12–18 years: initial dose of 600 micrograms/24h. The dose may be increased, as necessary, to 1.2mg/24h. Maximum recommended dose is 2.4mg/24h.

Notes

  • Not licensed for use in children for control of upper airways secretion and hypersalivation.

  • Excessive secretions can cause distress to the child but more often cause distress to those around him.

  • Treatment is more effective if started before secretions become too much of a problem.

  • Glycopyrronium does not cross the blood–brain barrier and therefore has fewer side effects than hyoscine hydrobromide, which is also used for this purpose. Also fewer cardiac side effects.

  • Slower-onset response than with hyoscine hydrobromide or butylbromide.

  • Oral absorption of glycopyrronium is very poor, with wide inter-individual variation.

  • For oral administration, injection solution may be given, or the tablets may be crushed and suspended in water. For administration via an enteral feeding tube, tablets may be dispersed in water. However, the coarse dispersion settles quickly. Flush the syringe and tube well to ensure all the dose is received.

  • Administration by CSCI: good compatibility data available with other commonly used palliative agents.

  • Available as: tablets (1mg and 2mg via an importation company, as the tablets are not licensed in the UK)—dosing often too inflexible for children and costly, and can be difficult to obtain; injection (200 micrograms/mL 1mL ampoules) can also be used po (unlicensed route); oral solution can also be prepared extemporaneously from glycopyrronium powder and obtained from a ‘specials’ manufacturer.

Haloperidol

Uses

  • Nausea and vomiting where the cause is metabolic or in difficult-to-manage cases such as end-stage renal failure.

  • Restlessness and confusion.

  • Intractable hiccups.

  • Psychosis, hallucination.

Dose and routes

By mouth for nausea and vomiting

  • Child 1 month to 12 years: initial dose of 50 micrograms/kg/24h (initial maximum 3mg/24h) in divided doses. The dose may be increased, as necessary, to a maximum of 170 micrograms/kg/24h in divided doses.

  • Child 12–18 years: 1.5mg od at night, increasing, as necessary, to 1.5mg bd; maximum 5mg bd.

By mouth for restlessness and confusion

  • Child 1 month to 12 years: initial dose of 50 micrograms/kg/24h (initial maximum 3mg/24h) in divided doses. The dose may be increased, as necessary, to a maximum of 170 micrograms/kg/24h in divided doses.

  • Child 12–18 years: 10–20 micrograms/kg every 8–12h; maximum 10mg/day.

By mouth for intractable hiccups

  • Child 1 month to 12 years: initial dose of 50 micrograms/kg/24h (initial maximum 3mg/24h) in divided doses. The dose may be increased, as necessary, to a maximum of 170 micrograms/kg/24h in divided doses.

  • Child 12–18 years: 1.5mg tds.

By continuous intravenous or subcutaneous infusion (for any indication)

  • Child 1 month to 12 years: initial dose of 25 micrograms/kg/24h (initial maximum 1.5mg/24h). The dose may be increased, as necessary, to a maximum of 85 micrograms/kg/24h.

  • Child 12–18 years: initial dose of 1.5mg/24h. The dose may be increased, as necessary, to a suggested maximum of 5mg/24h, although higher doses may be used under specialist advice.

Notes

  • D2 receptor antagonist and typical antipsychotic.

  • Not licensed for use in children with nausea and vomiting, restlessness and confusion, or intractable hiccups. Injection is licensed only for im administration in adults; iv and sc administration off-label (all ages).

  • Haloperidol can cause potentially fatal prolongation of the QT interval and torsades de pointes, particularly if given iv (off-label route) or at higher than recommended doses. Caution is required if any formulation of haloperidol is given to patients with an underlying predisposition, e.g. those with cardiac abnormalities, hypothyroidism, familial long QT syndrome, electrolyte imbalance, or taking other drugs known to prolong the QT interval. If iv haloperidol is essential, ECG monitoring during drug administration is recommended.

  • Dosages for restlessness and confusion are often higher.

  • Adult dosages can exceed 15mg/24h in severe agitation.

  • Oral doses are based on an oral bioavailability of ~50% of the parenteral route, i.e. oral doses ~2× parenteral.

  • Useful as long-acting—od dosing is often adequate.

  • Oral solutions may be administered via an enteral feeding tube.

  • Available as: tablets (500 micrograms, 1.5mg, 5mg, 10mg, 20mg), capsules (500 micrograms), oral liquid (1mg/mL, 2mg/mL), and injection (5mg/mL).

Hydromorphone

Uses

  • Alternative opioid analgesic for severe pain, especially if intolerant to other strong opioids.

  • Antitussive.

Dose and routes

Normally convert using OME from previous analgesia.

Use the following starting doses in opioid-naïve patient. The maximum dose stated applies to the starting dose only.

By mouth

  • Child 1–18 years: 30 micrograms/kg per dose; maximum 2mg per dose every 3–4h, increasing as required. Modified-release capsules with an initial dose of 4mg every 12h may be used from 12 years of age.

By intravenous or subcutaneous injection

  • Child 1–18 years: initially 15 micrograms/kg per dose slowly over at least 2–3min every 3–6h.

  • Convert from oral (halve the dose for equivalence).

Notes

  • Hydrated morphine ketone effects are common to the class of mu agonist analgesics.

  • Injection is not licensed in the UK. May be possible to obtain via a specialist importation company, but as hydromorphone is a CD, this is not a straightforward process.

  • Oral form licensed for use in children from 12 years of age with cancer pain.

  • Oral bioavailability 37–62% (wide inter-individual variation), onset of action 15min for sc, 30min for po. Peak plasma concentration 1h po. Plasma half-life 2.5h early phase, with a prolonged late phase. Duration of action 4–5h.

  • Potency ratios seem to vary more than for other opioids. This may be due to inter-individual variation in metabolism or bioavailability.

  • Conversion of po morphine to po hydromorphone: divide the morphine dose by 5–7.

  • Conversion of iv morphine to iv hydromorphone: divide the morphine dose by 5–7.

  • Dosage discontinuation: after short-term therapy (7–14 days), the original dose can be decreased by 10–20% of the original dose every 8h, increasing gradually the time interval. After long-term therapy, the dose should be reduced not more than 10–20% per week.

  • Caution in hepatic impairment; use at reduced starting doses.

  • Modified-release capsules are given 12-hourly.

  • Capsules (both types) can be opened, and contents sprinkled on soft food. Capsule contents must not, however, be administered via an enteral feeding tube, as likely to cause blockage.

  • Available as: capsules (1.3mg, 2.6mg) and modified-release capsules (2mg, 4mg, 8mg, 16mg, 24mg).

Hyoscine butylbromide

Uses

  • Adjuvant where pain is caused by spasm of the gastrointestinal or genitourinary tract.

  • Management of secretions, especially where drug crossing the blood–brain barrier is an issue.

Dose and routes

By mouth or intramuscular or intravenous injection

  • Child 1 month to 4 years: 300–500 micrograms/kg (maximum 5mg/dose) 3–4 times daily.

  • Child 5–12 years: 5–10mg 3–4 times daily.

  • Child 12–18 years: 10–20mg 3–4 times daily.

By continuous subcutaneous infusion

  • Child 1 month to 4 years: 1.5mg/kg/24h (maximum 15mg/24h).

  • Child 5–12 years: 30mg/24h.

  • Child 12–18 years: up to 60–80mg/24h.

  • Higher doses may be needed; doses used in adults range from 20 to 120mg/24h (maximum dose 300mg/24h).

Notes

  • Does not cross the blood–brain barrier (unlike hyoscine hydrobromide), hence no central antiemetic effect and does not cause drowsiness.

  • Tablets are not licensed for use in children <6 years old.

  • Injection is not licensed for use in children.

  • The injection solution may be given po or via an enteral feeding tube. If the tube exits in the jejunum, consider using parenteral therapy. Injection solution can be stored for 24h in the refrigerator.

  • iv injection should be given slowly over 1min and can be diluted with 5% glucose or 0.9% NaCl.

  • Available as: tablets (10mg) and injection (20mg/mL).

Hyoscine hydrobromide

Uses

  • Control of upper airways secretions and hypersalivation.

Dose and routes

By mouth or sublingual

  • Child 2–12 years: 10 micrograms/kg (maximum 300 micrograms single dose) qds.

  • Child 12–18 years: 300 micrograms qds.

By transdermal route

  • Child 1 month to 3 years: quarter of a patch every 72h.

  • Child 3–10 years: half of a patch every 72h.

  • Child 10–18 years: one patch every 72h.

By subcutaneous or intravenous injection or infusion

  • Child 1 month to 18 years: 10 micrograms/kg (maximum 600 micrograms) every 4–8h or CSCI/iv infusion 40–60 micrograms/kg/24h. Maximum suggested dose is 2.4mg in 24h, although higher doses are often used by specialist units.

Notes

  • Not licensed for use in children for control of upper airways secretion and hypersalivation.

  • Higher doses often used under specialist advice.

  • Can cause delirium or sedation (sometimes paradoxical stimulation) with repeated dosing. Constipating.

  • Apply the patch to a hairless area of skin behind the ear.

  • The patch can cause alteration of the pupil size on the side it is placed.

  • Some specialists advise that transdermal patches should not be cut—however, the manufacturers of Scopoderm TTS® patch have confirmed that it is safe to do this.

  • Injection solution may be administered po.

  • Available as: tablets (150 micrograms, 300 micrograms), patches (releasing 1mg/72h), and injection (400 micrograms/mL, 600 micrograms/mL). An oral solution is available via a ‘specials’ manufacturer.

Ibuprofen

Uses

  • Simple analgesic.

  • Pyrexia.

  • Adjuvant for musculoskeletal pain.

Dose and routes

By mouth

  • Neonate: 5mg/kg/dose every 12h.

  • Child 1–3 months: 5mg/kg 3–4 times daily, preferably after food.

  • Child 3–6 months: 50mg tds, preferably after food; in severe conditions, up to 30mg/kg daily in 3–4 divided doses.

  • Child 6 months to 1 year: 50mg 3–4 times daily, preferably after food; in severe conditions, up to 30mg/kg daily in 3–4 divided doses.

  • Child 1–4 years: 100mg tds, preferably after food. In severe conditions, up to 30mg/kg daily in 3–4 divided doses.

  • Child 4–7 years: 150mg tds, preferably after food. In severe conditions, up to 30mg/kg daily in 3–4 divided doses.

  • Child 7–10 years: 200mg tds, preferably after food. In severe conditions, up to 30mg/kg daily in 3–4 divided doses. Maximum daily dose 2.4g.

  • Child 10–12 years: 300mg tds, preferably after food. In severe conditions, up to 30mg/kg daily in 3–4 divided doses. Maximum daily dose 2.4g.

  • Child 12–18 years: 300–400mg 3–4 times daily, preferably after food. In severe conditions, the dose may be increased to a maximum of 2.4g/day.

Pain and inflammation in rheumatic diseases, including idiopathic juvenile arthritis

  • Child aged 3 months to 8 years and body weight >5kg: 30–40mg/kg daily in 3–4 divided doses, preferably after food. Maximum 2.4g daily.

In systemic juvenile idiopathic arthritis

  • Up to 60mg/kg daily in 4–6 divided doses, up to a maximum of 2.4g daily (off-label).

Notes

  • Will cause closure of ductus arteriosus; contraindicated in duct-dependent congenital heart disease.

  • Orphan drug licence for closure of ductus arteriosus in preterm neonate.

  • Not licensed for use in children under 3 months of age or weight <5kg.

  • Topical preparations and granules are not licensed for use in children.

  • Ibuprofen combines anti-inflammatory, analgesic, and antipyretic properties. It has fewer side effects than other NSAIDs, but its anti-inflammatory properties are weaker.

  • The risk of cardiovascular events secondary to NSAID use is undetermined in children. In adults, all NSAID use (including COX-2 selective inhibitors) can, to varying degrees, be associated with a small increased risk of thrombotic events (e.g. myocardial infarction and stroke), independent of baseline cardiovascular risk factors or duration of NSAID use; however, the greatest risk may be in those patients receiving high doses long-term. A small increased thrombotic risk cannot be excluded in children.

  • All NSAIDs are associated with gastrointestinal toxicity. In adults, evidence on the relative safety of NSAIDs indicates differences in the risks of serious upper gastrointestinal side effects—piroxicam and ketorolac are associated with the highest risk; indometacin, diclofenac, and naproxen are associated with intermediate risk, and ibuprofen with the lowest risk (although high doses of ibuprofen have been associated with intermediate risk).

  • Caution in asthma, and look out for symptoms and signs of gastritis.

  • Consider the use of a PPI with prolonged use of ibuprofen.

  • For administration via an enteral feeding tube, use a liquid preparation; dilute with an equal volume of water immediately prior to administration where possible.

  • Available as: tablets (200mg, 400mg, 600mg), capsule (300mg modified-release), oral syrup (100mg/5mL), granules (600mg/sachet), and spray, creams, and gels (5%).

Ipratropium bromide

Uses

  • Wheezing/breathlessness caused by bronchospasm.

Dose and routes

Nebulized solution

  • Child <1 year: 62.5 micrograms 3–4 times daily.

  • Child 1–5 years: 125–250 micrograms 3–4 times daily.

  • Child 5–12 years: 250–500 micrograms 3–4 times daily.

  • Child over 12 years: 500 micrograms 3–4 times daily.

Aerosol inhalation

  • Child 1 month to 6 years: 20 micrograms tds.

  • Child 6–12 years: 20–40 micrograms tds.

  • Child 12–18 years: 20–40 micrograms 3–4 times daily.

Notes

  • Inhaled product should be used with a suitable spacer device, and the child/carer should be given appropriate training.

  • In acute asthma, use via an oxygen-driven nebulizer.

  • In severe acute asthma, the dose can be repeated every 20–30min in the first 2h, then every 4–6h, as necessary.

  • Available as: nebulizer solution (250 micrograms in 1mL, 500 micrograms in 2mL) and aerosol inhaler (20 micrograms per metered dose).

Ketamine

Uses

  • Adjuvant to a strong opioid for neuropathic pain.

  • To reduce NMDA receptor wind-up pain and opioid tolerance.

Dose and routes

By mouth or sublingual

  • Child 1 month to 12 years: starting dose 150 micrograms/kg, as required or regularly 6- to 8-hourly; increase in increments of 150 micrograms/kg up to 400 micrograms/kg, as required. Doses equivalent to 3mg/kg have been reported in adults.

  • Over 12 years and adult: 10mg, as required or regularly 6- to 8-hourly; increase in steps of 10mg up to 50mg, as required. Doses up to 200mg qds reported in adults.

By continuous subcutaneous or intravenous infusion

  • Child 1 month to adult: starting dose 40 micrograms/kg/h. Increase according to response; usual maximum 100 micrograms/kg/h. Doses up to 1.5mg/kg/h in children and 2.5mg/kg/h in adults have been reported.

Notes

  • NMDA antagonist.

  • Specialist use only.

  • Not licensed for use in children with neuropathic pain.

  • Higher doses (bolus injection 1–2mg/kg, infusions 600–2700 micrograms/kg/h) used as an anaesthetic, e.g. for short procedures.

  • Sublingual doses should be prepared in a maximum volume of 2mL. The bitter taste may make this route unpalatable. Special preparations for sublingual use are available in the UK.

  • Enteral dose equivalents may be as low as one-third of iv or sc dose, because ketamine is potentiated by hepatic first-pass metabolism. Other papers quote a 1:1 sc to po conversion ratio.

  • Agitation, hallucinations, anxiety, dysphoria, and sleep disturbance are recognized side effects. These may be less common in children and when sub-anaesthetic doses are used.

  • Ketamine can cause urinary tract symptoms—frequency, urgency, dysuria, and haematuria. Consider discontinuing ketamine if these symptoms occur.

  • Caution in severe hepatic impairment; consider dose reduction.

  • Dilute in 0.9% saline for sc or iv infusion.

  • Can be administered as a separate infusion or by adding to opioid infusion/PCA/nurse-controlled analgesia (NCA).

  • Can also be used intranasally and as a topical gel.

  • Available as: injection (10mg/mL, 50mg/mL, 100mg/mL) and oral solution 50mg in 5mL (from a ‘specials’ manufacturer). Injection solution may be given po. Mix with a flavoured soft drink to mask the bitter taste.

Ketorolac

Uses

  • Short-term management of moderate to severe acute post-operative pain; limited evidence of extended use in chronic pain.

Dose and routes

Short-term management of moderate to severe acute post-operative pain (NB. licensed duration is a maximum of 2 days; not licensed for use in adolescents and children <16 years of age)

Intravenous bolus (over at least 15s) or intramuscular bolus

  • Child 1–16 years: initially 0.5–1mg/kg (maximum 10mg), then 500 micrograms/kg (maximum 15mg) every 6h, as required; maximum 60mg daily.

  • Child >16 years: initially 10mg, then 10–30mg every 4–6h, as required (up to every 2h during initial post-operative period); maximum 90mg daily (those weighing <50kg: maximum 60mg daily).

Chronic pain in palliative care (unlicensed indication; data limited and of poor quality; anecdotal reports of effectiveness for patients with bone pain unresponsive to oral NSAIDs)

Subcutaneous bolus

  • Child >16 years: 15–30mg/dose tds.

Continuous subcutaneous infusion

  • Child >16 years: initial dose of 60mg/24h. Increase, if necessary, by 15mg/24h to a maximum of 90mg/24h.

Notes

  • NSAID which has potent analgesic effects, with only moderate anti-inflammatory action.

  • Licensed only for the short-term management (maximum of 2 days) of moderate to severe acute post-operative pain in adults and adolescents from 16 years of age.

  • sc administration is an unlicensed route of administration.

  • Contraindications: previous hypersensitivity to ketorolac or other NSAIDs; history of asthma; active peptic ulcer or history of gastrointestinal bleeding; severe heart, hepatic, or renal failure; suspected or confirmed cerebrovascular bleeding or coagulation disorders. Do not use in combination with any other NSAID.

  • Dose in adults with mild renal impairment should not exceed 60mg/day.

  • All NSAIDs are associated with gastrointestinal toxicity. In adults, evidence on the relative safety of NSAIDs indicates ketorolac and piroxicam are associated with the highest risk. Use the lowest effective dose for the shortest time. In addition, consider use in combination with a gastroprotective drug, especially if ketorolac is used for a prolonged period (outside the licensed indication). Use of ketorolac in adults carries a 15 times increased risk of upper gastrointestinal complications, and a three times increased risk, compared with other non-selective NSAIDs.

  • In adults, all NSAID use can, to varying degrees, be associated with a small increased risk of thrombotic effects. The risk of cardiovascular effects secondary to NSAID use is undetermined in children, but, in adults, ketorolac is associated with the highest myocardial infarction risk of all NSAIDs.

  • Other potential adverse effects: very common (>10% of patients)—headache, dyspepsia, nausea, abdominal pain; common (1–10% of patients)—dizziness, tinnitus, oedema, hypertension, anaemia, stomatitis, abnormal renal function, pruritus, purpura, rash, bleeding, and pain at injection site. Risk of adverse effects likely to increase with prolonged use.

  • Drug interactions include: anticoagulants (contraindicated, as the combination may cause an enhanced anticoagulant effect); corticosteroids (increased risk of gastrointestinal ulceration of bleeding); diuretics (risk of reduced diuretic effect and increased risk of nephrotoxicity of NSAIDs); other potential nephrotoxic drugs.

  • Onset of action iv/im injection: 10–30min; maximal analgesia achieved within 1–2h and median duration of effect 4–6h.

  • sc injection can be irritant; therefore, dilute to the largest volume possible (0.9% NaCl suggested). Alkaline in solution, so high risk of incompatibility mixed with acidic drugs. Some data of compatibility in 0.9% saline with diamorphine or oxycodone. Incompatibilities include with cyclizine, glycopyrronium, haloperidol, levomepromazine, midazolam, and morphine.

  • Available as: injection (30mg/mL). Injection contains ethanol as an excipient.

  • Oral 10mg tablets and injection 10mg/mL no longer available in the UK (discontinued early 2013 due to lack of demand).

Lactulose

Uses

  • Constipation, faecal incontinence related to constipation.

  • Hepatic encephalopathy and coma.

Dose and routes

Constipation

By mouth: initial dose bd, then adjusted to suit the patient.

  • Neonate: 2.5mL/dose bd.

  • Child 1 month to 1 year: 2.5mL/dose 1–3 times daily.

  • Child 1–5 years: 5mL/dose 1–3 times daily.

  • Child 5–10 years: 10mL/dose 1–3 times daily.

  • Child 10–18 years: 15mL/dose 1–3 times daily.

Hepatic encephalopathy

  • Child 12–18 years: use 30–50mL tds as initial dose. Adjust dose to produce 2–3 soft stools per day.

Notes

  • Licensed for constipation in all age groups. Not licensed for hepatic encephalopathy in children.

  • Side effects may cause nausea and flatus, with colic especially at high doses. Initial flatulence usually settles after a few days.

  • Precautions and contraindications: galactosaemia, intestinal obstruction. Caution in lactose intolerance.

  • Use is limited, as macrogols are often better in palliative care. However, the volume per dose of macrogols is 5–10 times greater than lactulose and may not be tolerated in some patients.

  • Sickly taste.

  • Onset of action can take 36–48h.

  • May be taken with water and other drinks.

  • Relatively ineffective in opioid-induced constipation: need a stimulant.

  • 15mL/day is 14kcal, so unlikely to affect diabetics.

  • Does not irritate or directly interfere with gut mucosa.

  • Available as: oral solution (10g/15mL). Cheaper than Movicol® (macrogol).

Lansoprazole

Uses

  • GORD; erosive oesophagitis; prevention and treatment of NSAID gastric and oesophageal irritation; treatment of duodenal and gastric ulcer.

Dose and routes

Oral

  • Child body weight <30kg: 0.5–1mg/kg with maximum 15mg od in the morning.

  • Child body weight >30kg: 15–30mg od in the morning.

Notes

  • Lansoprazole is not licensed in the UK for infants, children, or adolescents. Lansoprazole is, however, licensed in the USA for use from 1 year of age. Exact doses limited by available formulations.

  • Lansoprazole is a gastric PPI. It inhibits the final stage of gastric acid formation by inhibiting the activity of H+/K+ ATPase of the parietal cells in the stomach. The inhibition is dose-dependent and reversible, and the effect applies to both basal and stimulated secretion of gastric acid.

  • For optimal effect, the single daily dose is best taken in the morning.

  • Lansoprazole should be taken at least 30min before food, as intake with food slows down the absorption and decreases the bioavailability.

  • The dose may be increased if symptoms do not fully resolve (consider increasing the single daily dose or bd dosing).

  • Studies in infants and children indicate they appear to need a higher mg/kg dose than adults to achieve therapeutic acid suppression.

  • There is some anecdotal experience that lansoprazole FasTab® may be halved to give a 7.5mg dose.

  • No dose adjustment is needed in patients with renal impairment. Reduction of dose (50%) is recommended in patients with moderate to severe hepatic impairment.

  • Hypomagnesaemia may develop with prolonged use.

  • Common adverse effects (>1 in 100 to <1 in 10): headache, dizziness, nausea, diarrhoea, stomach pain, constipation, vomiting, flatulence, dry mouth, pharyngitis, increase in liver enzyme levels, urticaria, itching, and rash.

  • Lansoprazole may interfere with absorption of drugs where gastric pH is critical to its bioavailability (e.g. atazanavir, itraconazole); may cause increase in digoxin levels and increase in plasma concentration of drugs metabolized by CYP3A4 (e.g. theophylline and tacrolimus). Drugs which inhibit or induce CYP2C19 or CYP3A4 may affect the plasma concentration of lansoprazole. Sucralfate and antacids may decrease the bioavailability of lansoprazole.

  • Capsules: capsules should be swallowed whole with liquid. For patients with difficulty swallowing, studies and clinical practice suggest that the capsules may be opened, and the granules mixed with a small amount of water or apple/tomato juice, or sprinkled onto a small amount of soft food (e.g. yoghurt, apple puree) to ease administration.

  • FasTab®: place on the tongue, and gently suck. FasTab® rapidly disperses in the mouth, releasing gastro-resistant microgranules which are then swallowed. FasTab® can be swallowed whole with water or mixed with a small amount of water, if preferred. FasTab® contains lactose and aspartame and should be used with caution in known phenylketonuria (PKU) patients.

  • For administration via an NG or gastrostomy tube, lansoprazole FasTab® can be dispersed in 10mL of water and administered via an 8Fr NG tube without blockage. For smaller-bore tubes, dissolve the contents of a lansoprazole capsule in 8.4% sodium bicarbonate before administration. If the tube becomes blocked, use sodium bicarbonate to dissolve any enteric-coated granules lodged in the tube. Lansoprazole less likely than omeprazole MUPS to cause blockage of small-bore tubes.

  • Available as: 15mg and 30mg capsules, and 15mg and 30mg orodispersible tablets including FasTab® (Zoton®).

Levomepromazine

Uses

  • Broad-spectrum antiemetic where the cause is unclear or where probably multifactorial.

  • Second-line if a specific antiemetic fails.

  • Severe pain unresponsive to other measures—may be of benefit in a very distressed patient.

  • Sedation for terminal agitation, particularly in end-of-life care.

Dose and routes

Used as antiemetic

By mouth

  • Child 2–12 years: initial dose 50–100 micrograms/kg, given od or bd. This dose may be increased, as necessary and as tolerated, not to exceed 1mg/kg/dose (or maximum of 25mg/dose), given od or bd.

  • Child 12–18 years: initial dose 3mg od or bd. This dose may be increased, as necessary and as tolerated, to a maximum of 25mg od or bd.

By continuous intravenous or subcutaneous infusion over 24h

  • Child 1 month to 12 years: initial dose of 100 micrograms/kg/24h, increasing, as necessary, to a maximum of 400 micrograms/kg/24h. Maximum 25mg/24h.

  • Child 12–18 years: initial dose of 5mg/24h, increasing, as necessary, to a maximum of 25mg/24h.

Used for sedation

By subcutaneous infusion over 24h

  • Child 1–12 years: initial dose of 350 micrograms/kg/24h (maximum initial dose 12.5mg), increasing, as necessary, up to 3mg/kg/24h.

  • Child 12–18 years: initial dose of 12.5mg/24h, increasing, as necessary, up to 200mg/24h.

Analgesia

  • In adults, stat dose 12.5mg/dose by mouth or sc. Titrate the dose according to response; usual maximum daily dose in adults is 100mg sc or 200mg by mouth.

Notes

  • Licensed for use in children with terminal illness for the relief of pain and accompanying anxiety and distress.

  • A low dose is often effective as antiemetic. Titrate up, as necessary. Higher doses are very sedative, and this may limit dose increases.

  • If the child is not stable on high dosage for nausea and vomiting, reconsider the cause, and combine with other agents.

  • Some experience in adults with low dose used buccally as antiemetic (e.g. 1.5mg tds as needed).

  • Can cause hypotension, particularly with higher doses. Somnolence and asthenia are frequent side effects.

  • Levomepromazine and its non-hydroxylated metabolites are reported to be potent inhibitors of cytochrome P450 2D6. Co-administration of levomepromazine and drugs primarily metabolized by the cytochrome P450 2D6 enzyme system may result in increased plasma concentrations of these drugs that could increase or prolong both their therapeutic and/or adverse effects.

  • Avoid, or use with caution, in patients with liver dysfunction or cardiac disease.

  • Tablets may be halved or quartered to obtain smaller doses. Tablets/segments may be dispersed in water for administration via an enteral feeding tube.

  • For sc infusion, dilute with 0.9% NaCl. WFI may also be used. The sc dose is considered to be twice as potent as that administered po.

  • Available as: tablets (25mg) and injection (25mg/mL). A 6mg tablet is also available via specialist importation companies. An extemporaneous oral solution may be prepared.

Lidocaine (lignocaine) patch

Uses

  • Localized neuropathic pain.

Dose and routes

Topical

  • Child 3–18 years: apply 1–2 plasters to affected area(s). Apply the plaster od for 12h, followed by a 12h plaster-free period (to help reduce the risk of skin reactions).

  • Adult 18 years or above: up to three plasters to affected area(s). Apply the plaster od for 12h, followed by a 12h plaster-free period (to help reduce the risk of skin reactions).

Notes

  • Not licensed for use in children or adolescents under 18 years.

  • Cut the plaster to size and shape of the painful area. Do NOT use on broken or damaged skin or near the eyes.

  • When lidocaine 5% medicated plaster is used according to the maximum recommended dose (three plasters applied simultaneously for 12h), about 3 ± 2% of the total applied lidocaine dose is systemically available, and similar for single and multiple administrations.

  • Maximum recommended number of patches in adults currently is three per application.

  • The plaster contains propylene glycol which may cause skin irritation. It also contains methyl parahydroxybenzoate and propyl parahydroxybenzoate which may cause allergic reactions (possibly delayed). ~16% of patients can be expected to experience adverse reactions. These are localized reactions due to the nature of the medicinal product.

  • The plaster should be used with caution in patients with severe cardiac impairment, severe renal impairment, or severe hepatic impairment.

  • A recent analysis by anatomic site of patch placement suggests that application to the head was tolerated less well, compared with the trunk and extremities.

  • Doses extrapolated from BNF 2012 March.

  • Available as: 700mg/medicated plaster (5% w/v lidocaine).

Lomotil® (co-phenotrope)

Uses

  • Diarrhoea from non-infectious cause.

Dose and routes

By mouth

  • Child 2–4 years: half tablet tds.

  • Child 4–9 years: one tablet tds.

  • Child 9–12 years: one tablet qds.

  • Child 12–16 years: two tablets tds.

  • Child 16–18 years: initially four tablets, then two tablets qds.

Notes

  • Not licensed for use in children <4 years.

  • Tablets may be crushed. For administration via an enteral feeding tube, tablets may be crushed and dispersed in water immediately before use. Young children are particularly susceptible to overdosage, and symptoms may be delayed, and observation is needed for at least 48h after ingestion. Overdose can be difficult to manage, with a mixed picture of opioid and atropine poisoning. Further, the presence of subclinical doses of atropine may give rise to atropine side effects in susceptible individuals.

  • Available only as: tablets of co-phenotrope (2.5mg diphenoxylate hydrochloride and 25 micrograms atropine sulfate).

Loperamide

Uses

  • Diarrhoea from non-infectious cause.

  • Faecal incontinence.

Dose and routes

By mouth

  • Child 1 month to 1 year: initial dose of 100 micrograms/kg bd, given 30min before feeds. Increase, as necessary, up to a maximum of 2mg/kg/day, given in divided doses.

  • Child 1–12 years: initial dose of 100 micrograms/kg (maximum single dose 2mg) 3–4 times daily. Increase, as necessary, up to a maximum of 1.25mg/kg/day, given in divided doses (maximum 16mg/day).

  • Child 12–18 years: initial dose of 2mg 2–4 times daily. Increase, as necessary, up to a maximum of 16mg/day, given in divided doses.

Notes

  • Not licensed for use in children with chronic diarrhoea.

  • Capsules not licensed for use in children <8 years.

  • Syrup not licensed for use in children <4 years.

  • Common side effects: constipation, nausea, flatulence.

  • As an antidiarrhoeal, loperamide is about 50 times more potent than codeine. It is longer-acting; maximum therapeutic impact may not be seen for 16–24h.

  • For NG or gastrostomy administration: use the liquid preparation, undiluted. Flush well after dosing. Alternatively, the tablets can be used without risk of blockage, although efficacy is unknown. Jejunal administration will not affect the therapeutic response to loperamide. However, owing to the potential osmotic effect of the liquid preparation, it may be appropriate to further dilute the dose with water immediately prior to administration.

  • Available as: tablets (2mg), orodispersible tablets (2mg), and oral syrup (1mg/5mL).

Lorazepam

Uses

  • Background anxiety.

  • Agitation and distress.

  • Adjuvant in cerebral irritation.

  • Background management of dyspnoea.

  • Muscle spasm.

  • Status epilepticus.

Dose and routes for all indications, except status epilepticus

By mouth

  • Child <2 years: 25 micrograms/kg 2–3 times daily.

  • Child 2–5 years: 500 micrograms 2–3 times daily.

  • Child 6–10 years: 750 micrograms tds.

  • Child 11–14 years: 1mg tds.

  • Child 15–18 years: 1–2mg tds.

Sublingual

  • Children of all ages: 25 micrograms/kg as a single dose. Increase to 50 micrograms/kg (maximum 1mg/dose), if necessary.

  • Usual adult dose: 500 micrograms—1mg as a single dose; repeat as required.

Notes

  • Not licensed for use in children for these indications other than status epilepticus.

  • Tablets licensed in children over 5 years for premedication; injection not licensed in children <12 years, except for treatment of status epilepticus.

  • Potency in the order of ten times that of diazepam per mg as anxiolytic/sedative.

  • Well absorbed sublingually, with rapid onset of effect. There may, however, be variable absorption by this route, with further variation possible, depending on the formulation used; fast effect.

  • Specific sublingual tablets are not available in the UK, but generic lorazepam tablets (specifically Genus, PVL, or TEVA brands) do dissolve in the mouth to be given sublingually.

  • Tablets may be dispersed in water for administration via an enteral feeding tube.

  • May cause drowsiness and respiratory depression, if given in large doses.

  • Caution in renal and hepatic failure.

  • Available as: tablets (1mg, 2.5mg) and injection (4mg in 1mL).

Macrogols: Movicol®

Uses

  • Constipation.

  • Faecal impaction.

  • Suitable for opioid-induced constipation.

Dose and routes (Movicol® Paediatric for those <12 years of age; Movicol® from 12 years of age)

By mouth for constipation or prevention of faecal impaction

  • Child under 1 year: half to one sachet daily.

  • Child 1–6 years: one sachet daily (adjust dose according to response; maximum four sachets daily).

  • Child 6–12 years: two sachets daily (adjust dose according to response; maximum four sachets daily).

  • Child 12–18 years: 1–3 sachets daily of adult Movicol®.

By mouth for faecal impaction

  • Child under 1 year: half to one sachet daily.

  • Child 1–5 years: two sachets on the first day, and increase by two sachets every 2 days (maximum eight sachets daily). Treat until impaction resolved, then switch to maintenance laxative therapy.

  • Child 5–12 years: four sachets on the first day, and increase by two sachets every 2 days (maximum 12 sachets daily). Treat until impaction resolved, then switch to maintenance laxative therapy.

  • Child 12–18 years: four sachets daily of adult Movicol®, then increase by two sachets daily to a maximum of eight adult Movicol® sachets daily. Total daily dose should be drunk within a 6h period. After disimpaction, switch to maintenance laxative therapy.

Notes

  • Not licensed for use in children <5 years with faecal impaction and <2 years with chronic constipation.

  • Need to maintain hydration. Caution if fluid or electrolyte disturbance.

  • Caution with high doses in those with impaired gag reflex, reflux oesophagitis, or impaired consciousness.

  • Mix powder with water: Movicol® Paediatric 60mL per sachet and adult Movicol® 125mL per sachet.

  • For administration via a feeding tube: dissolve the powder in water, as directed, and flush down the feeding tube. Flush well after dosing.

  • Macrogol oral powder is also available as alternative brands Laxido Orange® and Molaxole®, but these preparations are licensed for use only from 12 years of age.

Melatonin

Uses

  • Sleep disturbance due to disruption of circadian rhythm (not anxiolytic).

Dose and routes

By mouth

  • Child 1 month to 18 years: initial dose 2–3mg, increasing every 1–2 weeks, dependent on effectiveness, up to maximum 12mg daily.

Notes

  • Not licensed for use in children.

  • Specialist use only.

  • Some prescribers use a combination of immediate-release and modified-release tablets to optimize sleep patterns.

  • Immediate-release capsules may be opened, and the contents sprinkled on cold food, if preferred. Sustained-release capsules may also be opened, but the contents should not be chewed.

  • Only licensed formulation in the UK is 2mg modified-release tablets. Various unlicensed formulations, including an immediate-release preparation, are available from ‘specials’ manufacturers or specialist importing companies.

Methadone

(WARNING: requires additional training for dosing.)

Uses

  • Major opioid used for moderate to severe pain, particularly neuropathic pain and pain poorly responsive to other opioids.

  • Not normally used as first-line analgesia.

Caution

  • Methadone should only be commenced by practitioners experienced in its use.

  • This is due to wide inter-individual variation in response, very variable conversion ratios with other opioids, complex pharmacokinetics, and a long half-life.

  • Initial close monitoring is particularly important.

Dose and routes

In opioid-naïve children

By mouth, and subcutaneous and intravenous injection

  • Child 1–12 years: 100–200 micrograms/kg every 4h for first 2–3 doses, then every 6–12h (maximum dose 5mg/dose initially).

  • Methadone has a long and variable half-life, with potential to cause sedation, respiratory depression, and even death from secondary peak phenomenon.

  • Titration of methadone dosing must be done under close clinical observation of the patient, particularly in the first few days. Due to a large volume of distribution, higher doses are required for the first few days, while body tissues become saturated. Once saturation is complete, a smaller dose is sufficient. Continuing on the initial daily dose is likely to result in sedation within a few days, possible respiratory depression, and even death.

  • Doses may need to be reduced by up to 50% 2–3 days after the initial effective dose has been found to prevent adverse effects, due to tissue saturation and methadone accumulation. From then on, increments in methadone dosing should be approximately at weekly intervals, with a maximum increase of 50% (experienced practitioners may increase more frequently).

  • Continued clinical reassessment is required to avoid toxicity, as the time to reach steady-state concentration, following a change in dosing, may be up to 12 days.

  • For breakthrough pain, we would recommend using a short half-life opioid.

In opioid substitution/rotation or switch

Caution

Substitution, rotation, or switch to methadone is a specialist skill and should only be undertaken in close collaboration with practitioners experienced in its use. There is a risk of unexpected death through overdose.

Equianalgesic doses

Dose conversion ratios from other opioids are not static but are a function of previous opioid exposure and are highly variable.

Published tables of equianalgesic doses of opioids, established in healthy, non-opioid-tolerant individuals, indicate that methadone is 1–2 times as potent as morphine in single dose studies, but, in individuals on long-term (and high-dose) morphine, methadone is closer to ten times as potent as morphine; it can be 30 times more potent or occasionally even more. The potency ratio tends to increase, as the dose of morphine increases. If considering methadone, thought should be given to the potential difficulty of subsequently switching from methadone to another opioid.

Other opioids should be considered first if switching from morphine, due to unacceptable effects or inadequate analgesia.

Consultation with a pain clinic or specialist palliative care service is advised.

In adults, there are several protocols for opioid rotation to methadone which are not evidence-based in paediatrics.

  • In one approach, previous opioid therapy is completely stopped, before starting a fixed dose of methadone at variable dose intervals.

  • The other approach incorporates a transition period where the dose of the former opioid is reduced and partially replaced by methadone which is then titrated upwards.

It can be difficult to convert a short-half-life opioid to a methadone equivalent dose and vice versa. Current practice is usually to admit to a specialist inpatient unit for 5–6 days of regular treatment or titrate orally at home with close supervision.

Converting oral methadone to subcutaneous/intravenous or continuous subcutaneous infusion/continuous intravenous infusion methadone

  • Approximate dose ratios for switching between oral dosage and parenteral/sc form is 2:1 (oral:parenteral).

  • Calculate the total daily dose of po methadone, and halve it (50%). This will be the 24h parenteral/sc methadone dose.

  • Seek specialist guidance if mixing with any other drug.

  • If CSCI methadone causes a skin reaction, consider doubling the dilution and changing the syringe every 12h.

  • Administer iv methadone slowly over 3–5min.

Notes

  • Not licensed for use in children.

  • Data on methadone in paediatric patients are limited; known to have wide inter-individual pharmacokinetic variation.

  • Use methadone with caution, as methadone’s effect on respiration lasts longer than analgesic effects.

  • Side effects include: nausea, vomiting, constipation, dry mouth, biliary spasm, respiratory depression, drowsiness, muscle rigidity, hypotension, bradycardia, tachycardia, palpitation, oedema, postural hypotension, hallucinations, vertigo, euphoria, dysphoria, dependence, confusion, urinary retention, ureteric spasm, and hypothermia.

  • Following concerns regarding methadone and sudden death from prolongation of the QT interval or torsades de pointes (especially at high doses), it is recommended that patients have an ECG prior to initiation of treatment and regularly while on methadone, particularly if they have any risk factors or are having iv treatment of methadone.

  • Opioid antagonists naloxone and naltrexone will precipitate an acute withdrawal syndrome in methadone-dependent individuals. Naloxone will also antagonize the analgesic, CNS, and respiratory depressant effects of methadone.

  • Methadone has the potential for a number of significant drug interactions. Drugs that induce cytochrome P450 3A4 enzymes (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, some HIV drugs) will increase the rate of metabolism of methadone and potentially lead to reduced serum levels. Drugs that inhibit the system (e.g. amitriptyline, ciprofloxacin, fluconazole) may lead to increased serum levels of methadone.

  • Renal impairment: if severe (i.e. glomerular filtration rate (GFR) <10mL/min or serum creatinine >700 micromoles/L)—reduce methadone dose by 50%, and titrate according to response. Significant accumulation is not likely in renal failure, as elimination is primarily via the liver.

  • As methadone has a long half-life, infusion of naloxone may be required to treat opioid overdose.

  • Available as: linctus (2mg/5mL), mixture (1mg/mL), solution (1mg/mL, 5mg/mL, 10mg/mL, and 20mg/mL), tablets (5mg), and injection (10mg/mL).

Methylnaltrexone

Uses

  • Opioid-induced constipation when the response to other laxatives alone is inadequate and other relevant factors have been/are being addressed.

Dose and routes

Subcutaneous (usual route) or intravenous bolus

  • Child 1 month to 12 years: 0.15mg/kg (maximum 8mg) as a single dose.

  • Child >12 years, with weight 38–61kg: 8mg as a single dose.

  • Child >12 years, with weight 62–114kg: 12mg as a single dose.

  • Child >12 years, but with body weight <38kg: use 0.15mg/kg.

A single dose may be sufficient. However, repeat doses may be given, with a usual administration schedule of a single dose every other day. Doses may be given with longer intervals, as per clinical need. Patients may receive two consecutive doses (24h apart) only when there has been no response (no bowel movement) to the dose on the preceding day (one-third to half of patients given methylnaltrexone have a bowel movement within 4h, without loss of analgesia).

Notes

  • Mu opioid receptor antagonist that acts exclusively in the peripheral tissues, including the gastrointestinal tract (increasing bowel movement and gastric emptying), and does not affect the analgesic effects of opioids.

  • Not licensed for use in children or adolescents <18 years.

  • Not licensed for iv administration—usual route is sc.

  • Methylnaltrexone is contraindicated in cases of known or suspected bowel obstruction.

  • The onset of effect may be within 15–60min.

  • Common side effects include abdominal pain/colic, diarrhoea, flatulence, and nausea.

  • If administered by sc injection, rotate the site of injection. Do not inject into areas where the skin is tender, bruised, red, or hard.

  • Constipation in palliative care is usually multifactorial, and other laxatives are often required in addition.

  • Reduce dose by 50% in severe renal impairment.

  • Does not cross the blood–brain barrier.

  • Available as: single-use vial 12mg/0.6mL solution for sc injection (Relistor®).

Metoclopramide

To minimize the risk of neurological side effects associated with metoclopramide, the EMA in 2013 issued the following recommendations (NB. use of metoclopramide in palliative care was excluded from these recommendations. HOWEVER, caution should be exercised nevertheless):

  • use of metoclopramide is contraindicated in children younger than 1 year;

  • in children aged 1–18 years, metoclopramide should only be used as a second-line option for the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) and for treatment of established post-operative nausea and vomiting (PONV);

  • metoclopramide should only be prescribed for short-term use (up to 5 days).

Uses

  • Antiemetic if vomiting caused by gastric compression or hepatic disease.

  • Prokinetic for slow transit time (not in complete obstruction or with anticholinergics).

  • Hiccups.

Dose and routes

By mouth, intramusular injection, or intravenous injection (over at least 3min)

  • Neonate: 100 micrograms/kg every 6–8h (by mouth or iv only).

  • Child 1 month to 1 year, with body weight up to 10kg: 100 micrograms/kg (maximum 1mg/dose) bd.

  • Child 1–18 years: 100–150 micrograms/kg, repeated up to tds. The maximum dose in 24h is 500 micrograms/kg (maximum 10mg/dose).

If preferred, the appropriate total daily dose may be administered as a continuous sc or iv infusion over 24h.

Notes

  • Not licensed for use in infants <1 year of age.

  • Not licensed for continuous iv or sc infusion.

  • Metoclopramide can induce acute dystonic reactions such as facial and skeletal muscle spasms and oculogyric crises; children (especially girls, young women, and those under 10kg) are particularly susceptible. With metoclopramide, dystonic effects usually occur shortly after starting treatment and subside within 24h of stopping it.

  • iv doses should be administered as a slow bolus over at least 3min to reduce the risk of adverse effects.

  • Oral liquid formulations should be given via a graduated oral syringe to ensure dose accuracy in children. The oral liquid may be administered via an enteral feeding tube.

  • Can be irritant on sc administration; dilute well in 0.9% NaCl.

  • Available as: tablets (10mg), oral solution (5mg/5mL), and injection (5mg/mL).

Metronidazole topically

Uses

  • Odour associated with fungating wounds or lesions.

Dose and routes

By topical application

  • Apply to clean wound 1–2 times daily, and cover with non-adherent dressing.

  • Cavities: smear gel on paraffin gauze, and pack loosely.

Notes

  • Anabact® not licensed for use in children <12 years.

  • Metrogel® not licensed for use in children.

  • Available as: gel (Anabact® 0.75%, Metrogel® 0.75%).

Miconazole oral gel

Uses

  • Oral and intestinal fungal infection.

Dose and routes

By mouth

Prevention and treatment of oral candidiasis

  • Neonate: 1mL 2–4 times a day, smeared around the inside of the mouth after feeds.

  • Child 1 month to 2 years: 1.25mL qds, smeared around the inside of the mouth after food.

  • Child 2–18 years: 2.5mL qds after meals; retain near lesions before swallowing (orthodontic appliances should be removed at night and brushed with gel).

Prevention and treatment of intestinal candidiasis

  • Child 4 months to 18 years: 5mg/kg qds; maximum 250mg (10mL) qds.

Notes

  • Use after food, and retain near lesions before swallowing.

  • Treatment should be continued for 7 days after lesions have healed.

  • Not licensed for use in children under 4 months or during the first 5–6 months of life of an infant born preterm.

  • Infants and babies: the gel should not be applied to the back of the throat, due to possible choking. The gel should not be swallowed immediately, but kept in the mouth for as long as possible.

  • Available as: oral gel (24mg/mL in 15g and 80g tube).

  • A buccal tablet of miconazole is now available. Indicated for the treatment of oropharyngeal candidiasis in immunocompromised adults. Loramyc® 50mg muco-adhesive buccal tablets should be applied to the upper gum, just above the incisor tooth, od for 7–14 days. Currently, no experience in children but may be an option for adolescents.

Midazolam

Uses

  • Status epilepticus and terminal seizure control.

  • Breakthrough anxiety, e.g. panic attacks.

  • Adjuvant for pain of cerebral irritation.

  • Anxiety-induced dyspnoea.

  • Agitation at end of life.

Dose and routes

By oral or gastrostomy administration for anxiety or sedation

  • Child 1 month to 18 years: 500 micrograms/kg (maximum 20mg) as a single dose.

Buccal doses for acute anxiety

  • Any age: 100 micrograms/kg as a single dose (maximum initial dose 5mg).

By subcutaneous or intravenous infusion over 24h for anxiety

  • Dosages of 30–50% of terminal seizure control dose can be used to control anxiety, terminal agitation, and terminal breathlessness.

Buccal doses for status epilepticus

  • Neonate: 300 micrograms/kg as a single dose, repeated once if necessary.

  • Child 1–3 months: 300 micrograms/kg (maximum initial dose 2.5mg), repeated once if necessary.

  • Child 3 months to 1 year: 2.5mg, repeated once if necessary.

  • Child 1–5 years: 5mg, repeated once if necessary.

  • Child 5–10 years: 7.5mg, repeated once if necessary.

  • Child 10–18 years: 10mg, repeated once if necessary.

By buccal or intranasal administration for status epilepticus—should wait 10min before repeating dose.

NB. In single dose for seizures, midazolam is twice as potent as pr diazepam. For patients who usually receive pr diazepam for the management of status epilepticus, consider an initial dose of buccal midazolam that is 50% of their usual pr diazepam dose to minimize the risk of respiratory depression.

By subcutaneous or intravenous infusion over 24h for terminal seizure control

  • Neonate (seizure control): 150 micrograms/kg iv loading dose, followed by a continuous iv infusion of 60 micrograms/kg/h. Dose can be increased by 60 micrograms/kg/h every 15min until seizure controlled (maximum dose 300 micrograms/kg/h).

  • Child 1 month to 18 years: initial dose 50 micrograms/kg/h, increasing up to 300 micrograms/kg/h (maximum 100mg/24h or 150mg/24h in specialist units).

Notes

  • Buccal (Buccolam® oromucosal solution) midazolam is not licensed for use in infants <3 months of age. Midazolam injection is not licensed for use in seizure control or anxiety.

  • In single dose for sedation, midazolam is three times as potent as diazepam, and, in epilepsy, it is twice as potent as diazepam. (Diazepam gains in potency with repeated dosing because of prolonged half-life.)

  • Recommended sc/iv doses vary enormously in the literature. If in doubt, start at the lowest recommended dose, and titrate rapidly.

  • Onset of action by buccal and intranasal route 5–15min. For buccal administration, if possible, divide the dose, so half is given into one cheek, and the remaining half into the other cheek.

  • Onset of action by po or gastrostomy route 10–30min.

  • Onset of action by iv route 2–3min; sc route 5–10min.

  • Midazolam has a short half-life.

  • High doses can lead to paradoxical agitation.

  • Available as: oral solution (2.5mg/mL unlicensed), buccal liquid (5mg/mL Buccolam®), and injection (1mg/mL, 2mg/mL, 5mg/mL).

  • Other oral and buccal liquids (e.g. Epistatus® 10mg/mL) are also available from ‘specials’ manufacturers or specialist importing companies (unlicensed). NB. The buccal and oral formulations available may differ in strength—take care with prescribing.

Morphine

Uses

  • Major opioid (WHO step 2).

  • First-line oral opioid for pain.

  • Dyspnoea.

  • Cough suppressant.

Dose and routes

  • Opioid-naïve patient: use the following start doses (the maximum dose stated applies to the starting dose only).

  • Opioid conversion: convert using OME from the previous opioid.

By mouth or rectum

  • Child 1–3 months: initially 50 micrograms/kg every 4h, adjusted according to response.

  • Child 3–6 months: 100 micrograms/kg every 4h, adjusted according to response.

  • Child 6–12 months: 200 micrograms/kg every 4h, adjusted according to response.

  • Child 1–12 years: initially 200–300 micrograms/kg (initial maximum 5–10mg) every 4h, adjusted according to response.

  • Child 12–18 years: initially 5–10mg every 4h, adjusted according to response.

By single subcutaneous injection or intravenous injection (over at least 5min)

  • Neonate: initially 25 micrograms/kg every 6h, adjusted to response.

  • Child 1–6 months: initially 50–100 micrograms/kg every 6h, adjusted to response.

  • Child 6 months to 2 years: initially 100 micrograms/kg every 4h, adjusted to response.

  • Child 2–12 years: initially 100 micrograms/kg every 4h, adjusted to response; maximum initial dose of 2.5mg.

  • Child 12–18 years: initially 2.5–5mg every 4h, adjusted to response (maximum initial dose of 20mg/24h).

By continuous subcutaneous or intravenous infusion

  • Neonate: 5 micrograms/kg/h, adjusted according to response.

  • Child 1–6 months: 10 micrograms/kg/h, adjusted according to response.

  • Child 6 months to 18 years: 20 micrograms/kg/h (maximum initial dose of 20mg/24h), adjusted according to response.

Parenteral dose: 30–50% of oral dose if converting from oral dose of morphine.

Dyspnoea

  • 30–50% of the dose used for pain.

Notes

  • Oramorph® solution not licensed for use in children under 1 year; Oramorph® unit dose vials not licensed for use in children under 6 years; Sevredol® tablets not licensed for use in children under 3 years; Filnarine® SR tablets not licensed for use in children under 6 years; MST Continus® preparations licensed to treat children with cancer pain (age range not specified by manufacturer); MXL® capsules not licensed for use in children under 1 year; suppositories not licensed for use in children. Caution in renal or hepatic impairment.

  • Where opioid substitution or rotation is to morphine: use OME.

  • Particular side effects include urinary retention and pruritus in the paediatric setting, in addition to well-recognized constipation, nausea, and vomiting.

  • Morphine toxicity often presents as myoclonic twitching.

  • Rectal route should be avoided, if possible, and is usually contraindicated in children with low platelets and/or neutropenia.

  • In an emergency, when oral intake not appropriate, MST® tablets can be administered pr.

  • Administration via enteral feeding tubes: for immediate pain relief, use oral solution; no further dilution is necessary. The tube must be flushed well, following dosing, to ensure that the total dose is delivered. For sustained pain relief, use MST Continus® sachets, dispersed in at least 10mL of water. Flush the tube well, following dosing, to ensure that the total dose is delivered. Note that any granules left in the tube will break down over a period of time, and a bolus of morphine will be delivered when the tube is next flushed; this has resulted in a reported fatality. Ensure that the dose prescribed can be administered using whole sachets when possible. Use of Zomorph® capsules opened to release the granules should be done with caution in children, due to issues with dose accuracy, and the granules should only be administered via an adult-size gastrostomy.

  • Available as (all Schedule 2 CD, except oral solution of strength 10mg in 5mL):

    • tablets (10mg, 20mg, 50mg);

    • oral solution (10mg/5mL (POM), 100mg/5mL);

    • modified-release tablets and capsules 12-hourly (5mg, 10mg, 15mg, 30mg, 60mg, 100mg, 200mg);

    • modified-release suspension 12-hourly (20mg, 30mg, 60mg, 100mg, 200mg);

    • modified-release capsules 24-hourly (30mg, 60mg, 120mg, 150mg, 200mg);

    • suppositories (10mg, 15mg, 30mg);

    • injection (10mg/mL, 15mg/mL, 20mg/mL, 30mg/mL).

Nabilone

Uses

  • Nausea and vomiting caused by cytotoxic chemotherapy (not first- or second-line therapy).

  • For unresponsive nausea and vomiting to conventional antiemetics.

Dose and routes

By mouth

  • Adult dose: 1–2mg bd (maximum dose 6mg/day in 2–3 divided doses).

Notes

  • Not licensed for use in children.

  • Nabilone is a synthetic cannabinoid.

  • Individual variation, requiring close medical supervision on commencement and dose adjustments.

  • The effects of nabilone may persist for a variable and unpredictable period of time, following its oral administration. Adverse psychiatric reactions can persist for 48–72h, following cessation of treatment.

  • For specialist use only.

  • Available as: capsules (1mg). Schedule 2 CD.

Naloxone

Uses

  • Emergency use for reversal of opioid-induced respiratory depression or acute opioid overdose.

  • Constipation when caused by opioids if methylnaltrexone not available and laxatives have been ineffective.

Dose and routes

Reversal of respiratory depression due to opioid overdose

By intravenous injection (review diagnosis; further doses may be required if respiratory depression deteriorates)

  • Neonate: 10 micrograms/kg; if no response, give a subsequent dose of 100 micrograms/kg (then review diagnosis).

  • Child 1 month to 12 years: 10 micrograms/kg; if no response, give a subsequent dose of 100 micrograms/kg (then review diagnosis).

  • Child 12–18 years: 400 micrograms to 2mg; if no response, repeat at intervals of 2–3min to a maximum of 10mg total dose (then review diagnosis).

By subcutaneous or intramuscular injection only if intravenous route not feasible

  • As per iv injection, but onset slower and potentially erratic.

By continuous intravenous infusion, adjusted according to response

  • Neonate: rate adjusted to response (initially, rate may be set at 60% of the initial resuscitative iv injection dose per hour).

  • Child 1 month to 18 years: rate adjusted to response (initially, rate may be set at 60% of the initial resuscitative iv injection dose per hour).

  • The initial resuscitative iv injection dose is that which maintained satisfactory self-ventilation for at least 15min.

Opioid-induced constipation

By mouth

  • In adults, the following doses have been used: total daily dose po naloxone = 20% of morphine dose; titrate according to need; maximum single dose 5mg.

Notes

  • Potent opioid antagonist.

  • Not licensed for use in children with constipation.

  • Also see methylnaltrexone.

  • Naloxone acts within 2min of iv injection and within 3–5min of sc or im injection.

  • Although oral availability of naloxone is relatively low, be alert for opioid withdrawal symptoms, including recurrence of pain, at higher doses.

  • Available as: injection (20 micrograms/mL, 400 micrograms/mL, 1mg/mL).

Naproxen

Uses

  • Non-steroidal anti-inflammatory agent analgesic; relief of symptoms in inflammatory arthritis and treatment of acute musculoskeletal syndromes.

Dose and routes

  • Child 1 month to 18 years: 5mg/kg/dose bd (maximum 1g/day).

Doses up to 10mg/kg bd (not exceeding 1g daily) have been used in severe conditions. High doses should ideally be used only for a short period. In general, use the lowest effective dose for the shortest treatment duration possible.

Notes

  • Naproxen is licensed for use from 5 years of age for juvenile idiopathic arthritis; not licensed for use in children <16 years for other conditions.

  • Naproxen is contraindicated in patients with a history of hypersensitivity to any NSAID or in those with a coagulation disorder.

  • Use with caution in renal, cardiac, or hepatic failure, as this may cause a deterioration in renal function; the dose should be kept as low as possible, and renal function monitored. Avoid use if GFR <20mL/min/1.73m2 and in those with severe hepatic or heart failure.

  • Generally, naproxen is regarded as combining good efficacy with a low incidence of side effects.

  • The risk of cardiovascular events secondary to NSAID use is undetermined in children. In adults, COX-2 selective inhibitors, diclofenac (150mg daily), and ibuprofen (2.4g daily) are associated with an increased risk of thrombotic effects (e.g. myocardial infarction and stroke). Naproxen (in adults 1g daily) is associated with a lower thrombotic risk. The greatest risk may increase with dose and duration of exposure, so the lowest effective dose should be used for the shortest possible duration of time.

  • All NSAIDs are associated with gastrointestinal toxicity. In adults, evidence on the relative safety of NSAIDs indicates differences in the risks of serious upper gastrointestinal side effects—piroxicam and ketorolac are associated with the highest risk; indometacin, diclofenac, and naproxen are associated with intermediate risk, and ibuprofen with the lowest risk. Children appear to tolerate NSAIDs better than adults, and gastrointestinal side effects are less common, although they do still occur and can be significant.

  • Other potential side effects include headache, dizziness, vertigo, fluid retention, and hypersensitivity reactions.

  • The antipyretic and anti-inflammatory actions of naproxen may reduce fever and inflammation, therefore reducing their utility as diagnostic signs.

  • Potential drug interactions include warfarin (increase in INR); and diuretics, ACE inhibitors, and angiotensin II antagonists (increased risk of compromised renal function). Naproxen is a substrate of CYP1A2 and CYP2C8/9 and can increase the plasma concentrations of methotrexate and lithium.

  • Naproxen tablets may be crushed before administration and can be mixed with water for administration via a feeding tube. However, naproxen is poorly soluble in water, and the tablet must be crushed to a fine powder before mixing with water to avoid tube blockage. There may be better choices of NSAID if administration via a feeding tube is necessary. Enteric-coated naproxen tablets should be swallowed whole, and NOT be crushed or chewed. Naproxen should be taken with or after food.

  • Available as: tablets (250mg and 500mg), enteric-coated tablets (250mg and 500mg), and oral suspension (25mg/mL, available only as a ‘special’ from specials manufacturers).

Nystatin

Uses

  • Oral and perioral fungal infection.

Dose and routes

By mouth

  • Neonate: 100 000 units qds.

  • Child 1 month to 18 years: 100 000 units qds.

Notes

  • Licensed from 1 month of age for treatment. Neonates—nystatin is licensed for prophylaxis against oral candidosis at a dose of 1mL daily.

  • Retain near lesions before swallowing.

  • Administer after food or feeds.

  • Treatment for 7 days and should be continued for 48h after lesions have healed.

  • Available as: oral suspension (100 000 units/mL, 30mL with pipette).

Octreotide

Uses

  • Bleeding from oesophageal or gastric varices.

  • Nausea and vomiting.

  • Intestinal obstruction.

  • Intractable diarrhoea.

  • Also used for hormone-secreting tumours, ascites, and bronchorrhoea.

Dose and routes

Bleeding from oesophageal varices

By continuous intravenous or subcutaneous infusion

  • Child 1 month to 18 years: 1 microgram/kg/h. Higher doses may be required initially. When there is no active bleeding, reduce dose over 24h. Usual maximum dose is 50 micrograms/h.

Nausea and vomiting, intestinal obstruction, and intractable diarrhoea

  • By continuous iv or sc infusion: doses up to 1 microgram/kg/h have been used, but experience is limited. Do not stop abruptly—discontinue at a reducing rate.

Notes

  • Not licensed for use in children.

  • Administration: for iv injection or infusion, dilute with 0.9% NaCl to a concentration of 10–50% (i.e. not less than 1:1 and not more than 1:9 by volume). For sc bolus injections, may be administered neat, but this can be painful (this can be reduced if the ampoule is warmed in the hand to body temperature before injection). For sc infusion, dilute with 0.9% NaCl.

  • Avoid abrupt withdrawal.

  • Available as: injection for sc or iv administration (50 micrograms/mL, 100 micrograms/mL, 200 micrograms/mL, 500 micrograms/mL). Also available as depot injection for im administration every 28 days (10mg, 20mg, and 30mg Sandostatin Lar®). Recommend specialist palliative care advice.

Olanzapine

Uses

  • Psychoses; delirium; agitation; nausea and vomiting; anorexia when all other treatments have failed.

Dose and routes

Oral

Psychoses/mania

  • Child <12 years and <25kg: initial dose 2.5mg at night.

  • Child <12 years and >25kg: initial dose 2.5–5mg at night.

  • Child 12–18 years: initial dose 5mg at bedtime.

Increase gradually, as necessary and as tolerated, to a maximum of 20mg/day, given usually as a single dose at night.

Agitation/delirium

  • Child <12 years: initial dose 1.25mg at night and prn.

  • Child 12–18 years: initial dose 2.5mg at night and prn.

Increase gradually, as necessary and as tolerated, to maximum of 10mg/day.

Nausea and vomiting, and anorexia

  • Child <12 years: initial dose 1.25mg (or 0.625mg if 2.5mg tablets can be cut into quarters) at night and prn.

  • Child 12–18 years: initial dose 1.25–2.5mg at night and prn.

Dose may be increased, as necessary and as tolerated, to a suggested maximum of 7.5mg/day.

Notes

  • Olanzapine is not licensed for use in children and adolescents <18 years of age, although there is general acknowledgement of ‘off-label’ use in adolescents for the treatment of psychosis and schizophrenia and mania associated with bipolar disorder.

  • Use in the treatment of agitation/delirium, nausea and vomiting, and anorexia in palliative care are all ‘off-label’ indications.

  • Olanzapine is an atypical (second-generation) antipsychotic agent and antagonist of D1, D2, D3, D4, 5HT2A, 5HT3, 5HT6, histamine-1, and muscarinic receptors.

  • Olanzapine has five times the affinity for 5HT2 receptors than for D2 receptors, resulting in fewer extrapyramidal side effects.

  • Activity of olanzapine at multiple receptors is similar to methotrimeprazine, and therefore it has a potential role in the treatment of nausea and vomiting refractory to standard medication.

  • Use with caution in those with cardiovascular disease or epilepsy (and conditions predisposing to seizures).

  • Very common (>10% of patients) adverse effects: weight gain, elevated triglyceride levels, increased appetite, sedation, increased ALT and AST levels, decreased bilirubin, and increased gamma-glutamyl transpeptidase (GGT) and plasma prolactin levels. Common (1–10% of patients) adverse effects: elevated cholesterol levels, dry mouth.

  • Rare, but potentially serious, adverse effects include neuroleptic malignant syndrome and neutropenia. Hyperglycaemia and sometime diabetes can occur.

  • Dose titration should be slow to minimize sedation.

  • A greater magnitude of weight gain and lipid and prolactin alterations have been reported in adolescents, compared to adults. If prolonged use is likely, consider the monitoring of blood lipids, weight, fasting blood glucose, and prolactin. Consider an ECG and BP measurement before initiation.

  • Consider a lower starting dose (maximum 5mg in adults) in patients with renal and/or hepatic impairment.

  • Olanzapine has good oral bioavailability, with peak plasma concentrations occurring within 5–8h. Absorption is not affected by food. Long elimination half-life of ~33h. Onset of actions is hours to days in delirium, and days to weeks in psychoses.

  • Olanzapine does not inhibit or induce the main CYP450 isoenzymes. Olanzapine is metabolized by CYP1A2; therefore, drugs/substances that specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine, e.g. carbamazepine, fluvoxamine, nicotine.

  • Orodispersible tablets: place in the mouth where the tablet will rapidly disperse in saliva or disperse in a full glass of water (or other drink) immediately before administration. May be dispersed in water for administration via an NG or gastrostomy feeding tube. Some anecdotal experience that 5mg orodispersible tablets may be halved to give a 2.5mg dose. Halve immediately before administration, and do not save the remaining half for a future dose.

  • Coated tablets: swallow whole with liquid, or crushed and mixed with soft food.

  • Orodispersible tablets contain aspartame and may be harmful for people with PKU.

  • Coated tablets contain lactose.

  • Available as: tablets (2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg) and orodispersible tablets (5mg, 10mg, 15mg, 20mg).

Omeprazole

Uses

  • Gastro-oesophageal reflux.

  • Acid-related dyspepsia.

  • Treatment of duodenal and gastric ulcers.

  • Gastrointestinal prophylaxis (e.g. with combination NSAID/steroids).

Dose and routes

By mouth

  • Neonate: 700 micrograms/kg od; increase, if necessary, to a maximum of 1.4mg/kg od (maximum dose 2.8mg/kg od).

  • Child 1 month to 2 years: 700 micrograms/kg od; increase, if necessary, to a maximum of 3mg/kg od (maximum dose 20mg od).

  • Child body weight 10–20kg: 10mg od; increase, if necessary, to a maximum of 20mg od.

  • Child body weight >20kg: 20mg od; increase, if necessary, to a maximum of 40mg od.

Intravenous (by injection over 5min or by infusion over 20–30min)

  • Child 1 month to 12 years: initially 500 micrograms/kg (maximum 20mg) od; increase, if necessary, to 2mg/kg (maximum 40mg) od.

  • Child 12–18 years: 40mg od.

Notes

  • Oral formulations are not licensed for use in children, except for severe ulcerating reflux oesophagitis in children >1 year.

  • Injection not licensed for use in children under 12 years.

  • Many children with life-limiting conditions have GORD and may need to continue with treatment long-term.

  • Can cause agitation.

  • Occasionally associated with electrolyte disturbance.

  • For oral administration, tablets can be dispersed in water or with fruit juice or yoghurt. Capsules can be opened and mixed with fruit juice or yoghurt.

  • Administer with care via enteral feeding tubes to minimize risk of blockage. Capsules may be opened, and contents dispersed in 8.4% sodium bicarbonate for administration. Dispersible tablets disintegrate to give a dispersion of small granules. The granules settle quickly and may block fine-bore feeding tubes (less than 8Fr).

  • Available as: MUPS tablets (10mg, 20mg, 40mg), capsules (10mg, 20mg, 40mg), iv injection (40mg), iv infusion (40mg), and oral suspension available as special order (10mg/5mL).

Ondansetron

Uses

  • Antiemetic, if vomiting caused by chemotherapy or radiotherapy.

  • May have a use in managing opioid-induced pruritus.

Dose and routes

Prevention and treatment of chemotherapy- and radiotherapy-induced nausea and vomiting.

By intravenous infusion over at least 15min

  • Child 6 months to 18 years: either 5mg/m2 immediately before chemotherapy (maximum single dose 8mg), then give by mouth, or 150 micrograms/kg immediately before chemotherapy (maximum single dose 8mg), repeated every 4h for two further doses, then give by mouth; maximum total daily dose 32mg.

By mouth following intravenous administration

NB. Oral dosing can start 12h after iv administration.

  • Child 6 months to 18 years:

    • body surface area <0.6m2or body weight 10kg or less: 2mg every 12h for up to 5 days (maximum total daily dose 32mg);

    • body surface area 0.6–1.2m2 or greater or body weight over 10kg: 4mg every 12h for up to 5 days (maximum total daily dose 32mg);

    • body surface area >1.2m2or body weight over 40kg: 8mg every 12h for up to 5 days (maximum total daily dose 32mg).

Nausea and vomiting

By mouth or slow iv injection over 2–5min or by iv infusion over 15min.

  • Child 1–18 years: 100–150 micrograms/kg/dose every 8–12h. Maximum single dose 4mg.

Notes

  • Ondansetron injection is licensed for the management of CINV in children aged ≥6 months, and for the prevention and treatment of PONV in children (as a single dose) aged ≥1 month. Oral ondansetron is licensed from 6 months of age for the management of CINV, but the oral formulation is not recommended for PONV in children due to a lack of data.

  • Ondansetron prolongs the QT interval in a dose-dependent manner. In addition, post-marketing cases of torsades de pointes have been reported in patients using ondansetron. Avoid ondansetron in patients with congenital long QT syndrome. Ondansetron should be administered with caution to patients who have or may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure, or bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation or electrolyte abnormalities.

  • Hypokalaemia and hypomagnesaemia should be corrected prior to ondansetron administration.

  • Repeat iv doses of ondansetron should be given no less than 4h apart.

  • Can cause constipation and headache.

  • For iv infusion, dilute to a concentration of 320–640 micrograms/mL with 5% glucose or 0.9% NaCl or Ringer’s solution; give over at least 15min.

  • Available as: tablets (4mg, 8mg), oral lyophilisate (4mg, 8mg), oral syrup (4mg/5mL), and injection (2mg/mL, 2mL and 4mL ampoules).

Oxycodone

Uses

  • Alternative opioid for severe pain.

  • Pain of all types, unless opioid-insensitive.

Dose and routes

  • Opioid switch: convert using OME from the previous opioid.

  • Use the following starting doses in the opioid-naïve patient. The maximum dose stated applies to the starting dose only.

By mouth

Conversion

  • po morphine 1.5:po oxycodone 1.

    • i.e. 15mg morphine:10mg oxycodone.

  • Child 1–12 months: initial dose 50–125 micrograms/kg every 4–6h.

  • Child 1–12 years: initial dose 125–200 micrograms/kg (maximum single dose 5mg) every 4–6h.

  • Child 12–18 years: starting dose 5mg every 4–6h.

  • Titrate as for morphine: increase the dose, if necessary, according to severity of pain.

  • Modified-release tablets, child 8–12 years: initial dose 5mg every 12h, increased if necessary.

  • Modified-release tablets, child 12–18 years: initial dose 10mg every 12h, increased if necessary.

By intravenous injection, subcutaneous injection, or continuous subcutaneous infusion

Conversion

  • po to iv or sc oxycodone single bolus dose injection: divide the po oxycodone dose by 1.5.

  • po to CSCI of oxycodone over 24h: divide the total daily dose of po oxycodone by 1.5.

  • sc/iv morphine to sc/iv oxycodone ratio is ~1:1, i.e. use the same dose.

  • Reason behind odd conversion ratio is bioavailability and rounding factors for safety.

Notes

  • Opioid analgesic.

  • Not licensed for use in children.

  • It is important to prescribe breakthrough analgesia which is 5–10% of the total 24h dose given every 1–4h.

  • It is moderately different from morphine in its structure, making it a candidate for opioid substitution.

  • Caution in hepatic or renal impairment.

  • Oxycodone injection may be given iv or sc as a bolus or by infusion. For CSCI, dilute with WFI, 0.9% NaCl, or 5% glucose.

  • Oxycodone liquid may be administered via an enteral feeding tube.

  • Schedule 2 CD.

  • Available as: tablets and capsules (5mg, 10mg, 20mg), liquid (5mg/5mL, 10mg/mL), modified-release tablets (5mg, 10mg, 15mg, 20mg, 30mg, 40mg, 80mg, 120mg), and injection (10mg/mL and 50mg/mL).

Oxygen

Uses

  • Breathlessness caused by hypoxaemia.

  • Palliative care for symptom relief, including recognition of potential placebo effect.

Dose and routes

By inhalation through nasal cannula

  • Flow rates of 1–2.5L/min, adjusted according to response. This will deliver between 24% and 35% oxygen, depending on the patient’s breathing pattern and other factors. Lower flow rates may be appropriate, particularly for preterm neonates.

By inhalation through face mask

  • Percentage inhaled oxygen is determined by the oxygen flow rate and/or type of mask; 28% oxygen is usually recommended for continuous oxygen delivery.

Notes

  • Oxygen saturations do not necessarily correlate with the severity of breathlessness. Where self-report is not possible, observation of the work of breathing is a more reliable indicator of breathlessness.

  • Frequent or continuous measurement of oxygen saturations may lead to an over-reliance on technical data and distract from evaluation of the child’s overall comfort, symptom relief, and well-being.

  • Target oxygen saturations of 92–96% may be appropriate in acute illness but are not necessarily appropriate for palliative care. More usual target oxygen saturations are above 92% in long-term oxygen therapy, and 88–92% in children at risk of hypercapnic respiratory failure. Lower saturation levels may be tolerated in children with cyanotic congenital heart disease.

  • It is important to be clear about the overall aims of oxygen treatment and realistic saturation levels for an individual child, as this will affect decisions about target oxygenation.

  • In cyanotic congenital heart disease, oxygen has little effect in raising SaO2 and is not generally indicated, although the degree of polycythaemia may be reduced. Pulmonary hypertension, in the early stages, may respond to oxygen, so it may be appropriate in the palliative care setting.

  • Moving air, e.g. from a fan, may be equally effective in reducing the sensation of breathlessness when the child is not hypoxaemic.

  • Nasal cannulae are generally preferable, as they allow the child to talk and eat with minimum restrictions. However, continuous nasal oxygen can cause drying of the nasal mucosa and dermatitis.

  • Oxygen administration via a mask can be claustrophobic.

  • The duration of supply from an oxygen cylinder will depend on the size of the cylinder and flow rate.

  • An oxygen concentrator is recommended for patients requiring >8h of oxygen therapy per day.

  • Liquid oxygen is more expensive but provides a longer duration of portable oxygen supply. Portable oxygen concentrators are now also available.

  • If necessary, two concentrators can be Y-connected to supply very high oxygen concentrations.

  • Higher concentrations of oxygen are required during air travel.

  • Home oxygen order forms (HOOFs) and further information available from <mouse symbol> www.bprs.co.uk/oxygen.html.

  • A secondary supply of oxygen for children spending a prolonged time away from home requires a second HOOF, available from the above website, e.g. short breaks, holiday, or extended periods with other relatives.

Pamidronate (disodium)

Uses

  • Adjuvant analgesic for bone pain caused by metastatic disease.

  • Adjuvant analgesic for bone pain in neurological and neuromuscular disorders, particularly due to osteopenia or osteoporosis.

  • Tumour-induced hypercalcaemia.

  • Treatment of secondary osteoporosis to reduce fracture risk.

NB. Evidence base is poor, but growing, for these uses in children. Seek specialist advice before use.

Dose and routes

  • For bone pain (metastatic bone disease or osteopenia) and secondary osteoporosis, an effect on pain should be seen within 2 weeks but may need a year before definitive assessment. Continue dosing for as long as effective and tolerated or until substantial decline in performance status.

By intravenous infusion

  • 1mg/kg as a single dose, infused over 4–6h, and repeated monthly as required; concentration not exceeding 60mg in 250mL, OR

  • 1mg/kg infused over 4–6h on 3 consecutive days and repeated every 3 months as required; concentration not exceeding 60mg in 250mL.

For malignant hypercalcaemia (seek specialist advice)

By intravenous infusion

  • 1mg/kg infused over 6h; concentration not exceeding 60mg in 250mL. Then repeated, as indicated, by corrected serum calcium.

Notes

  • Not licensed for use in children. Well tolerated by children, but long-term effects unknown.

  • Bisphosphonates have been used for some years in adults with bone metastases. It is becoming clear that they have a role in the wider causes of bone pain seen in children, particularly with neurological conditions.

  • Current guidelines suggest an initial dose be given as an inpatient. Subsequent doses could be given at home, if the necessary medical and nursing support is available. May have worsening of pain at first.

  • iv zoledronic acid can also be used.

  • po risedronate and po alendronate—limited use for these indications, due to poor and variable bioavailability.

  • If the iv route is unavailable, bisphosphonates can be administered by CSCI over 12–24h, together with sc hydration.

  • Many bisphosphonates are available in different formulations, including oral, although absorption tends to be poor by the oral route and further reduced by food or fluids other than plain water.

  • Caution: monitor renal function and electrolytes; ensure adequate hydration.

  • Prolonged hypocalcaemia and hypomagnesaemia may occur with concurrent use of an aminoglycoside and a bisphosphonate. Consider calcium and vitamin D oral supplements to minimize potential risk of hypocalcaemia for those with mainly lytic bone metastases and at risk of calcium or vitamin D deficiency (e.g. through malabsorption or lack of exposure to sunlight).

  • Risk of renal impairment is increased by concurrent use with other nephrotoxic drugs.

  • Risk of atypical femoral fractures and of osteonecrosis, especially of jaw if pre-existing pathology. Recommend dental check pre-administration.

  • Anecdotal risk of iatrogenic osteopetrosis with prolonged use (if prolonged use is likely, precede with dual-energy X-ray absorptiometry (DEXA) scan and investigation of calcium metabolism).

  • Available as: injection vials for infusion of various volumes, at 3mg/mL, 6mg/mL, 9mg/mL, and 15mg/mL.

Paracetamol

Uses

  • Mild to moderate pain.

  • Pyrexia.

Dose and routes

The recommended indications and doses of paracetamol have been revised to take account of MHRA and Toxbase advice that paracetamol toxicity may occur with doses between 75mg and 150mg/kg/day (ingestion of over 150mg/kg/day is regarded as a definite risk of toxicity).

By mouth

  • Neonate 28–32 weeks corrected gestational age: 20mg/kg as a single dose, then 10–15mg/kg every 8–12h, as necessary (maximum 30mg/kg/day in divided doses).

  • Neonates over 32 weeks corrected gestational age: 20mg/kg as a single dose, then 10–15mg/kg every 6–8h, as necessary (maximum 60mg/kg/day in divided doses).

  • Child 1 month–6 years: 20–30mg/kg as a single dose, then 15–20mg/kg every 4–6h, as necessary (maximum 75mg/kg/day in divided doses).

  • Child 6–12 years: 20–30mg/kg (max 1g) as a single dose, then 15–20mg/kg every 4–6h, as necessary (maximum 75mg/kg/day or 4g/day in divided doses).

  • Over 12 years: 15–20mg/kg (maximum 500mg to 1g) every 4–6h, as necessary (maximum 4g/day in divided doses).

Rectal

  • Neonate 28–32 weeks corrected gestational age: 20mg/kg as a single dose, then 10–15mg/kg every 12h, as necessary (maximum 30mg/kg/day in divided doses).

  • Neonates over 32 weeks corrected gestational age: 30mg/kg as a single dose, then 15–20mg/kg every 8h, as necessary (maximum 60mg/kg/day in divided doses).

  • Child 1–3 months: 30mg/kg as a single dose, then 15–20mg/kg every 4–6h, as necessary (maximum 75mg/kg/day in divided doses).

  • Child 3 months to 12 years: 30mg/kg as a single dose (maximum 1g), then 15–20mg/kg every 4–6h, as necessary (maximum 75mg/kg/day or 4g/day in divided doses).

  • Over 12 years: 15–20mg/kg (maximum 500mg to 1g) every 4–6h, as necessary (maximum 4g/day in divided doses).

Intravenous: as infusion over 15min

  • Preterm neonate over 32 weeks corrected gestational age: 7.5mg/kg every 8h, maximum 25mg/kg/day.

  • Neonate: 10mg/kg every 4–6h (maximum 30mg/kg/day).

  • Infant and child body weight <10kg: 10mg/kg every 4–6h (maximum 30mg/kg/day).

  • Child body weight 10–50kg: 15mg/kg every 4–6h (maximum 60mg/kg/day).

  • Body weight over 50kg: 1g every 4–6h (maximum 4g/day).

Notes

  • Not licensed for use in children under 2 months by mouth; not licensed for use in preterm neonates by iv infusion; not licensed for use in children under 3 months by rectum; doses for severe symptoms not licensed; paracetamol oral suspension 500mg/5mL not licensed for use in children under 16 years.

  • Oral and licensed rectal preparations are licensed for use in infants from 2 months for post-immunization pyrexia (single dose of 60mg which may be repeated once after 4–6h, if necessary) and from 3 months as antipyretic and analgesic.

  • iv paracetamol is licensed for short-term treatment of moderate pain and of fever when other routes not possible.

  • Consider use of non-pharmacological measures to relieve pain, as an alternative or in addition to analgesics.

  • Hepatotoxic in overdose or prolonged high doses.

  • In moderate renal impairment, use the maximum frequency of 6-hourly; in severe renal impairment, maximum frequency of 8-hourly.

  • Many children and young people with life-limiting illness have low weight for their age. The doses above are therefore quoted mainly by weight, rather than by age (unlike most of the entries in the BNF and BNFC), in order to minimize the risk of overdosing in this patient group.

  • Onset of action 15–30min po, 5–10min iv (analgesia), 30min iv (antipyretic). Duration of action 4–6h po and iv. Oral bioavailability 60–90%. Rectal bioavailability about two-thirds of oral. However, rectal absorption is now known to be erratic and incomplete, and results in slower absorption than oral administration (except in babies when the oral preparation used rectally speeds absorption, compared with suppositories). Elimination is slower in babies under 3 months.

  • Dispersible tablets have high sodium content (over 14mmol per tablet), so caution with regular dosing (consider using the liquid preparation instead).

  • For administration via an enteral feeding tube: use tablets dispersed in water for intragastric or intrajejunal administration. If the sodium content is problematic, use the liquid formulation. This can be used undiluted for intragastric administration; however, the viscosity of the paediatric liquid preparations is very high; it is difficult to administer these suspensions via a fine-bore tube without dilution. If administering intrajejunally, dilute with at least an equal quantity of water to reduce osmolarity and viscosity.

  • For management of feverish illness in children, see updated NICE clinical guideline CG160. (Consider using either paracetamol or ibuprofen in children with fever who appear distressed, and consider changing to the other agent if distress is not alleviated. But do not use antipyretic agents with the sole aim of reducing the body temperature.) However, a recent Cochrane systematic review states ‘there is some evidence that both alternating and combined antipyretic therapy may be more effective at reducing temperatures than monotherapy alone’. For babies over 3 months, ibuprofen may be preferable to paracetamol, since asthma seems commoner in children who experienced early paracetamol exposure.

  • Available as: tablets and caplets (500mg), capsules (500mg), soluble tablets (120mg, 500mg), oral suspension (120mg/5mL, 250mg/5mL), suppositories (60mg, 125mg, 250mg, 500mg, and other strengths available from ‘specials’ manufacturers or specialist importing companies), and iv infusion (10mg/mL in 50mL and 100mL vials).

Paraldehyde

Uses

  • Treatment of prolonged seizures and status epilepticus.

Dose and routes

By rectal administration (dose shown is for premixed enema 50:50 with olive oil).

  • Neonate: 0.8mL/kg as a single dose.

  • 1 month to 18 years: 0.8mL/kg (maximum 20mL) as a single dose.

Notes

  • Rectal administration may cause irritation.

  • Contraindicated in gastric disorders and colitis.

  • Paraldehyde enema for rectal use is an unlicensed formulation and route of administration.

  • Available as: paraldehyde enema—premixed solution of paraldehyde in olive oil in equal volumes from ‘special-order’ manufacturers or specialist importing companies.

Phenobarbital

Uses

  • Adjuvant in pain of cerebral irritation.

  • Control of terminal seizures.

  • Sedation.

  • Epilepsy, including status epilepticus. Commonly used first-line for seizures in neonates (phenytoin or benzodiazepine are the main alternatives).

  • Agitation refractory to midazolam in end-of-life care.

Dose and routes

Status epilepticus/terminal seizures/agitation

Loading dose

  • po, iv, or sc injection:

    • all ages: 20mg/kg/dose (maximum 1g) administered over 20min if by iv or sc injection (but see Formulary Notes below).

Subcutaneous or intravenous injection or infusion

  • Neonates for control of ongoing seizures: 2.5–5mg/kg od or bd as maintenance.

  • Child 1 month to 12 years: 2.5–5mg/kg (maximum single dose 300mg) od or bd or may be given as a continuous infusion over 24h.

  • Child 12–18 years: 300mg bd or may be given as a continuous infusion over 24h.

Epilepsy

By mouth

  • Neonates for control of ongoing seizures: 2.5–5mg/kg od or bd as maintenance.

  • Child 1 month to 12 years: 1–1.5mg/kg bd, increased by 2mg/kg daily, as required (usual maintenance dose 2.5–4mg/kg od or bd).

  • Child 12–18 years: 60–180mg od.

Notes

  • Not licensed for agitation in end-of-life care.

  • Single loading dose is required for initiation of therapy; administer via the enteral route, if possible. Loading dose can be administered iv over 20min or as a slow sc loading dose; however, the volume of the resultant solution will limit the rate at which an sc bolus can be administered.

  • Loading dose essential to reach steady state quickly and avoid late toxicity due to accumulation.

  • For patients already on po phenobarbital but needing parenteral treatment, doses equivalent to the patient’s usual total daily dose of po phenobarbital can be used.

  • Elimination half-life of 2–6 days in adults, 1–3 days in children.

  • Phenobarbital induces various enzymes of the CYP450 system and thus may reduce the plasma concentrations of concomitant drugs that are metabolized by this system.

  • Tablets may be crushed for administration, if preferred.

  • Use a separate site to commence sc infusion. sc bolus injections should be avoided, because they can cause tissue necrosis due to the high pH.

  • It is essential to dilute the injection in ten times the volume of water for injection before iv or sc injection (i.e. to the concentration of 20mg/mL).

  • Available as: tablets (15mg, 30mg, 60mg), oral elixir (15mg/5mL), and injection (15mg/mL, 60mg/mL, and 200mg/mL). The licensed oral elixir of 15mg in 5mL contains alcohol 38%, and it is preferable to obtain an alcohol-free oral liquid via one of the specials manufacturers.

Phenytoin

Uses

  • Epilepsy (third- or fourth-line oral anti-epileptic), including for status epilepticus.

  • Neuropathic pain (effective, at least short-term, but not used first-line).

Dose and routes

All forms of epilepsy (including tonic–clonic, focal, and neonatal seizures), except absence seizures; neuropathic pain.

Oral or slow intravenous injection

  • Neonate: initial loading dose by slow iv injection 18mg/kg, THEN by mouth 2.5–5mg/kg bd, adjusted according to response and plasma phenytoin levels. Usual maximum 7.5mg/kg bd.

  • Child 1 month to 12 years: initial dose of 1.5–2.5mg/kg bd, then adjust according to response and plasma phenytoin levels to 2.5–5mg/kg bd as a usual target maintenance dose. Usual maximum dose of 7.5mg/kg bd or 300mg daily.

  • Child 12–18 years: initial dose of 75–150mg bd, then adjusted according to response and plasma phenytoin levels to 150–200mg bd as a usual target maintenance dose. Usual maximum dose of 300mg bd.

Status epilepticus and acute symptomatic seizures

Slow intravenous injection or infusion

  • Neonate: 20mg/kg loading dose over at least 20min, then 2mg/kg/dose (over 30min) every 8–12h as a usual maintenance dose in the first week of life. Adjust according to response, and older babies may need higher doses. After the first dose, po doses usually as effective as iv in babies over 2 weeks old.

  • Child 1 month to 12 years: 20mg/kg loading dose over at least 20min, then 2.5–5mg/kg bd usual maintenance dose.

  • Child 12–18 years: 20mg/kg loading dose over at least 20min, then up to 100mg (over 30min) 3–4 times daily usual maintenance dose.

Notes

  • Licensed status: suspension 90mg in 5mL is a ‘special’ and unlicensed. Other preparations are licensed for use in children as an anticonvulsant (age range not specified).

  • Phenytoin acts as a membrane stabilizer.

  • It has a narrow therapeutic index and an unpredictable half-life, and the relationship between the dose and plasma drug concentration is non-linear. The rate of elimination is also very variable, especially in the first few weeks and months of life. Co-treatment with commonly used drugs can significantly alter the half-life.

  • Phenytoin has numerous interactions with other drugs due to hepatic enzyme induction. Long-term use is associated with significant side effects. It is no more effective than other anti-epileptics and hence not usually used first-line, although it does enable rapid titration.

  • Continuous ECG and BP monitoring required during iv administration.

  • Oral bioavailability of 90–95% is roughly equivalent to iv, plasma half-life 7–42h. Poor rectal absorption.

  • Absorption is exceptionally poor via the jejunal route.

  • Reduce dose in hepatic impairment. Monitor carefully if reduced albumin or protein binding, e.g. in renal failure.

  • Caution: cross-sensitivity is reported with carbamazepine.

  • Avoid abrupt withdrawal.

  • Consider vitamin D supplementation in patients who are immobilized for long periods or who have inadequate sun exposure or dietary intake of calcium.

  • Before and after administration, flush iv line with 0.9% NaCl.

  • For iv injection, give into a large vein at a rate not exceeding 1mg/kg/min (maximum 50mg/min).

  • For iv infusion, dilute to a concentration not exceeding 10mg/mL with 0.9% NaCl, and give into a large vein through an in-line filter (0.22–0.50 micrometres) at a rate not exceeding 1mg/kg/min (maximum 50mg/min); complete administration within 1h of preparation.

  • Prescriptions for oral preparations should include the brand name and be of consistent preparation type, to ensure consistency of drug delivery.

  • Preparations containing phenytoin sodium are not bioequivalent to those containing phenytoin base (such as Epanutin Infatabs® and Epanutin® suspension); 100mg of phenytoin sodium is approximately equivalent in therapeutic effect to 92mg phenytoin base. The dose is the same for all phenytoin products when initiating therapy; however, if switching between these products, the difference in phenytoin content may be clinically significant. Care is needed when making changes between formulations, and plasma phenytoin concentration monitoring is recommended.

  • Bioavailability may be reduced unpredictably by enteral feeds and/or NG tube feeds, so flush with water to enhance absorption; interrupt enteral feeding for at least 1–2h before and after giving phenytoin, and maintain similar timings and regimes from day to day.

  • Available as: tablets (phenytoin sodium 100mg, generic), capsules (Epanutin® phenytoin sodium 25mg, 50mg,100mg, 300mg), Epanutin Infatabs® (chewable tablets of phenytoin base 50mg), oral suspension (Epanutin® phenytoin base 30mg/5mL, and 90mg/5mL phenytoin base available as an ‘unlicensed special’), and injection (phenytoin sodium 50mg/mL, generic).

Phosphate (rectal enema)

Uses

  • Constipation refractive to other treatments.

Dose and routes

By rectal enema

  • Child 3–7 years: 45–65mL od.

  • Child 7–12 years: 65–100mL od.

  • Child 12–18 years: 100–128mL od.

Notes

  • Maintain good hydration, and watch for electrolyte imbalance.

  • Contraindicated in acute gastrointestinal conditions (including gastrointestinal obstruction, inflammatory bowel disease, and conditions associated with increased colonic absorption).

  • Use only after specialist advice.

  • Available as Phosphate enema BP formula B in 128mL with a standard or long rectal tube (NB. alternative Fleet® Ready-to-use Enema requires slightly different dosing: 40–60mL for ages 3–7y, 60–90mL for ages 7–12y, and 90–118mL for ages 12–18y).

Promethazine

Uses

  • Sleep disturbance.

  • Mild sedation.

  • Antihistamine.

  • Can also be used to treat nausea and vomiting, and vertigo.

Dose and routes (for promethazine hydrochloride)

By mouth

Symptomatic relief of allergy

  • Child 2–5 years: 5mg bd or 5–15mg at night.

  • Child 5–10 years: 5–10mg bd or 10–25mg at night.

  • Child 10–18 years: 10–20mg 2–3 times daily or 25mg at night, increased to 25mg bd, if necessary.

Sedation (short-term use)

  • Child 2–5 years: 15–20mg at night.

  • Child 5–10 years: 20–25mg at night.

  • Child 10–18 years: 25–50mg at night.

Nausea and vomiting (particularly in anticipation of motion sickness)

  • Child 2–5 years: 5mg bd.

  • Child 5–10 years: 10mg bd.

  • Child 10–18 years: 20–25mg bd.

Notes

  • Antimuscarinic phenothiazine antihistamine, also with D2 antagonist activity.

  • Not for use in under 2 years due to risk of fatal respiratory depression.

  • Note drug interactions, particularly causing increased antimuscarinic and sedative effects.

  • Caution in epilepsy.

  • Can be effective for up to 12h. Drowsiness may wear off after a few days of treatment.

  • For use by feeding tube: the elixir is slightly viscous so can be mixed with an equal volume of water to reduce viscosity and resistance to flushing. Tablets will disintegrate if shaken in water for 5min.

  • Available as: promethazine hydrochloride tablets (10mg, 25mg), oral elixir (5mg/5mL), and injection (25mg/mL). (Promethazine teoclate tablets also available, 25mg, licensed for nausea, vomiting, and labyrinthine disorders. Dosing slightly different.)

Quinine sulfate

Uses

  • Leg cramps.

Dose and routes

By mouth

  • Not licensed or recommended for children, as no experience.

  • Adult dose: quinine sulfate 200mg at bedtime, increased to 300mg if necessary.

Notes

  • Not licensed for use in children for this condition.

  • Moderate evidence indicates it to be more effective than placebo in reducing frequency and intensity of cramp.

  • Regulatory agencies consider that, given that alternatives to quinine are available, the risks associated with its use are unacceptably high. Rare, but serious, side effects include thrombocytopenia and haemolytic uraemic syndrome. Also very toxic in overdose and has serious interactions with warfarin and digoxin. Therefore, MHRA advises that quinine should only be used if the four criteria are all met: treatable causes have been ruled out; non-pharmacological measures have failed; cramps regularly cause loss of sleep; and they are very painful or frequent. Patients should be monitored for signs of thrombocytopenia in the early stages of treatment.

  • If used, treatment should be discontinued after 4 weeks if ineffective, and interrupted every 3 months to re-evaluate benefit.

  • Available as: tablets (200mg quinine sulfate).

Ranitidine

Uses

  • Gastro-oesophageal reflux.

  • Treatment of gastritis, benign gastric, and duodenal ulcers.

  • Gastro-protection (e.g. with combination NSAID/steroids).

  • Other conditions requiring reduction in gastric acid.

Dose and routes

By mouth

  • Neonate: 2–3mg/kg tds (absorption unreliable).

  • Child 1–6 months: 1mg/kg tds, increasing, if necessary, to maximum 3mg/kg tds.

  • Child 6 months to 3 years: 2–4mg/kg bd.

  • Child 3–12 years: 2–4mg/kg (maximum single dose 150mg) bd. Dose may be increased up to 5mg/kg (maximum 300mg/dose) bd in severe GORD.

  • Child 12–18 years: 150mg bd or 300mg at night. May be increased, if necessary, in moderate to severe GORD to 300mg bd or 150mg qds for up to 12 weeks.

By slow iv injection, diluted to 2.5mg/mL, and given over at least 3min (some adult centres give as sc injection—unlicensed route):

  • neonate: 0.5–1mg/kg every 6–8h (may need 2mg/kg 8-hourly, as variable first-pass metabolism affects uptake);

  • child 1 month to 18 years: 1mg/kg (maximum 50mg) every 6–8h (may be given as an intermittent infusion at a rate of 25mg/h).

Notes

  • Oral formulations not licensed for use in children <3 years; injection not licensed for children under 6 months.

  • Use gastric pH to judge best dose in early infancy.

  • PPIs, H2 antagonists, and prokinetics all relieve symptoms of non-ulcer dyspepsia and acid reflux, PPIs being the most effective. PPIs and ‘double-dose’ H2 antagonists are effective at preventing NSAID-related endoscopic peptic ulcers. Adding a bedtime dose of H2 antagonist to a high-dose PPI may improve nocturnal acid reflux, but evidence is poor.

  • Time to peak plasma concentration is 2–3h, half-life 2–3h, duration of action 8–12h.

  • Ranitidine may increase the plasma concentration of midazolam.

  • May cause rebound hyperacidity at night.

  • Via feeding tubes, use effervescent tablets as first choice, unless sodium content is a concern. Use oral liquid as alternative. (Standard tablets do not disperse readily in water.)

  • Can use iv, if needed, in severe nausea and vomiting. Some centres use sc doses bd to qds.

  • Available as: tablets and effervescent tablets (150mg, 300mg), oral solution (75mg/5mL), and injection (25mg/mL).

Risperidone

Uses

  • Dystonia and dystonic spasms refractory to first- and second-line treatment.

  • Psychotic tendency/crises in Batten’s disease.

  • Has antiemetic activity (some experience in refractory nausea and vomiting in adults; not evaluated in children).

  • Treatment of mania or psychosis under specialist supervision.

Dose and routes

Oral

  • Child 5–12 years (weight 20–50kg): 250 micrograms od; increasing, if necessary, in steps of 250 micrograms on alternate days to a maximum of 750 micrograms daily.

  • Child 12 years or over (>50kg): 500 micrograms od; increasing in steps of 500 micrograms on alternate days to a maximum of 1.5mg daily.

    • In juvenile Batten’s disease, may need 500 micrograms daily, increasing to 1.5mg tds during crises with hallucinations—this dose can be reduced or stopped, as symptoms settle (episodes usually last 1–6 weeks).

Notes

  • Not licensed for use in children for these indications. Risperidone is licensed for the short-term symptomatic treatment (up to 6 weeks) of persistent aggression in conduct disorder in children from the age of 5 years.

  • 99% bioavailable; 1–2h to peak plasma concentration. Onset of action hours to days in delirium; days to weeks in psychosis. Plasma half-life 24h. Duration of action 12–48h.

  • Caution in epilepsy and cardiovascular disease; extrapyramidal symptoms less frequent than with older antipsychotic medications; withdraw gradually after prolonged use. Risperidone can cause significant weight gain.

  • Initial and subsequent doses should be halved in renal or hepatic impairment.

  • Tablets disintegrate in water within 5min for easy administration via enteral feeding tubes. The oral liquid is simple to administer via a feeding tube.

  • Available as: tablets (500 micrograms, 1mg, 2mg, 3mg, 4mg, 6mg), orodispersible tablets (500 micrograms, 1mg, 2mg, 3mg, 4mg), and liquid (1mg/mL).

Salbutamol

Uses

  • Wheezing/breathlessness caused by bronchospasm.

  • Also used in hyperkalaemia, for prevention and treatment of chronic lung disease in premature infants, and sometimes in muscular disorders or muscle weakness (seek specialist advice, not covered here).

Dose and routes

For exacerbation of reversible airway obstruction and prevention of allergen- or exercise-induced bronchospasm

(NB. See separate detailed guidance in standard texts for use in acute asthma.)

Aerosol inhalation

  • Child 1 month to 18 years: 100–200 micrograms (1–2 puffs) for persistent symptoms up to qds.

Nebulized solution

  • Neonate: 1.25–2.5mg up to qds.

  • Child 1 month to 18 years: 2.5–5mg up to qds.

Oral preparations (but use by inhalation preferred for treatment of bronchospasm)

  • Child 1 month to 2 years: 100 micrograms/kg (maximum 2mg) 3–4 times daily.

  • Child 2–6 years: 1–2mg 3–4 times daily.

  • Child 6–12 years: 2mg 3–4 times daily.

  • Child 12–18 years: 2–4mg 3–4 times daily.

Notes

  • Salbutamol is not licensed for use in hyperkalaemia; syrup and tablets are not licensed for use in children <2 years; modified-release tablets are not licensed for use in children <3 years; injection is not licensed for use in children.

  • In palliative care, if airflow obstruction is suspected, a pragmatic approach may be to give a trial (e.g. 1–2 weeks) of a bronchodilator and evaluate the impact on symptoms. Spirometry should normally be used to confirm a possible underlying asthma diagnosis.

  • Salbutamol has not been shown to be effective in children <2 years, presumably due to the immaturity of the receptors; ipratropium may be more helpful in those <1–2 years.

  • For an acute episode, many paediatricians now advise multi-dosing of salbutamol 100 micrograms up to ten times, via a spacer where practicable for the patient, instead of a nebulizer.

  • Side effects: increased heart rate; feeling ‘edgy’ or agitated; tremor.

  • The side effects listed above may prevent use, in which case ipratropium bromide is a good alternative.

  • Inhaled product should be used with a suitable spacer device, and the child/carer should be given appropriate training. Inhaler technique should be explained and checked. The HFA (hydrofluoroalkane) propellant now used in multi-dose inhalers tends to clog the nozzle, so weekly cleaning is recommended.

  • Salbutamol nebules are intended to be used undiluted. However, if prolonged delivery time (>10min) is required, the solution may be diluted with sterile 0.9% NaCl. Salbutamol can be mixed with a nebulized solution of ipratropium bromide.

  • Available as: nebulizer solution (2.5mg in 2.5mL, 5mg in 2.5mL), respirator solution (5mg in 1mL), and aerosol inhalation (100 micrograms/puff) by metered dose inhaler (MDI), with various spacer devices. Various types of dry powder inhaler are also available. Also available as salbutamol tablets (costly) 2mg and 4mg, modified-release capsules 4mg and 8mg, and oral solution 2mg/5mL. Preparations for injection (500 micrograms/mL) and iv infusion (1mg/mL) are also available.

Senna

Uses

  • Constipation.

Dose and routes

By mouth

Initial doses which can be adjusted according to response and tolerance.

  • Child 1 month to 2 years: 0.5mL/kg (maximum 2.5mL) of syrup od.

  • Child 2–6 years: 2.5–5mL of syrup a day.

  • Child 6–12 years: 5–10mL a day of syrup or 1–2 tablets at night or 2.5–5mL of granules.

  • Child 12–18 years: 10–20mL a day of syrup or 2–4 tablets at night or 5–10mL of granules.

Notes

  • Syrup is not licensed for use in children <2 years, and tablets/granules are not licensed for use in children <6 years.

  • Stimulant laxative.

  • Onset of action 8–12h.

  • Initial dose should be low, then increased, if necessary.

  • Doses can be exceeded on specialist advice.

  • Granules can be mixed in hot milk or sprinkled on food.

  • Oral liquid may be administered via an enteral feeding tube.

  • Available as: tablets (7.5mg sennoside B), oral syrup (7.5mg/5mL sennoside B), and granules (15mg/5mL sennoside B).

Sodium citrate

Uses

  • Constipation where osmotic laxative indicated.

Dose and routes

Micolette Micro-enema®

Enema, sodium citrate 450mg, sodium lauryl sulfoacetate 45mg, glycerol 625mg, together with citric acid, potassium sorbate, and sorbitol in a viscous solution, in 5mL.

  • By rectum, child 3–18 years: 5–10mL as a single dose.

Micralax Micro-enema®

Enema, sodium citrate 450mg, sodium alkylsulfoacetate 45mg, sorbic acid 5mg, together with glycerol and sorbitol in a viscous solution, in 5mL.

  • By rectum, child 3–18 years: 5mL as a single dose.

Relaxit Micro-enema®

Enema, sodium citrate 450mg, sodium lauryl sulfate 75mg, sorbic acid 5mg, together with glycerol and sorbitol in a viscous solution, in a 5mL single-dose pack with nozzle.

  • By rectum: child 1 month to 18 years: 5mL as a single dose (insert only half nozzle length in a child under 3 years).

Notes

  • For under 3 years, insert only half nozzle length.

  • Available as: micro-enema (5mL).

Sodium picosulfate

Uses

  • Constipation.

Dose and routes

By mouth

  • Child 1 month–4 years: initial dose of 2.5mg od, increasing, if necessary, according to response to a suggested maximum of 10mg daily.

  • Child 4–18 years: initial dose of 2.5mg od, increasing, if necessary, according to response to a suggested maximum of 20mg daily.

Notes

  • Elixir is licensed for use in children of all ages; capsules are not licensed for use in children <4 years of age.

  • Acts as a stimulant laxative.

  • Onset of action 6–12h.

  • Effectiveness dependent upon breakdown by gut flora—previous effectiveness may therefore be lost during courses of antibiotics and ensuing altered gut flora.

  • For administration via an enteral feeding tube: use the liquid preparation; dilute with an equal volume of water prior to administration. Sodium picosulfate reaches the colon without any significant absorption; therefore, the therapeutic response will be unaffected by jejunal administration.

  • Available as: elixir (5mg/5mL) and capsules (2.5mg).

Sucralfate

Uses

  • Stress ulcer prophylaxis.

  • Prophylaxis against bleeding from oesophageal or gastric varices; adjunct in the treatment of: oesophagitis with evidence of mucosal ulceration, gastric or duodenal ulceration, upper gastrointestinal bleeding of unknown cause.

Dose and routes

Oral

Stress ulcer prophylaxis, prophylaxis against bleeding from oesophageal or gastric varices

  • Child 1 month to 2 years: 250mg 4–6 times daily.

  • Child 2–12 years: 500mg 4–6 times daily.

  • Child 12–15 years: 1g 4–6 times daily.

  • Child 15–18 years: 1g six times daily (maximum 8g/day).

Oesophagitis with evidence of mucosal ulceration, or gastric or duodenal ulceration

  • Child 1 month to 2 years: 250mg 4–6 times daily.

  • Child 2–12 years: 500mg 4–6 times daily.

  • Child 12–15 years: 1g 4–6 times daily.

  • Child 15–18 years: 2g bd (on rising and at bedtime) or 1g qds (1h before meals and at bedtime) taken for 4–6 weeks (up to 12 weeks in resistant cases); maximum 8g daily.

Notes

  • Not licensed for use in children <15 years; tablets are not licensed for prophylaxis of stress ulceration.

  • Administer 1h before meals.

  • Spread doses evenly throughout waking hours.

  • Bezoar formation: following reports of bezoar formation associated with sucralfate, the CSM has advised caution in seriously ill patients, especially those receiving concomitant enteral feeds or those with predisposing conditions such as delayed gastric emptying.

  • Caution—absorption of aluminium from sucralfate may be significant in patients on dialysis or with renal impairment.

  • Tablets may be crushed and dispersed in water.

  • Administration of sucralfate suspension and enteral feeds via an NG or gastrostomy tube should be separated by at least 1h. In rare cases, bezoar formation has been reported when sucralfate suspension and enteral feeds have been given too closely together.

  • Caution—sucralfate oral suspension may block fine-bore feeding tubes.

  • Available as: oral suspension (1g in 5mL) and tablets (1g).

Temazepam

Uses

  • Sleep disturbance where anxiety is a cause.

Dose and routes

By mouth

  • Adult: 10–20mg at night. Dose may be increased to 40mg at night in exceptional circumstances.

Notes

  • Not licensed for use in children.

  • Oral solution may be administered via an enteral feeding tube.

  • Available as: tablets (10mg, 20mg) and oral solution (10mg/5mL).

  • Schedule 3 CD.

Tizanidine

Uses

  • Skeletal muscle relaxant.

  • Chronic severe muscle spasm or spasticity.

Dose and routes

  • Child 18 months to 7 years: 1mg/day; increase, if necessary, according to response.

  • Child 7–12 years: 2mg/day; increase, if necessary, according to response.

  • Child >12 years: as per adult dose—initially 2mg, increasing in increments of 2mg at intervals of 3–4 days. Give the total daily dose in divided doses up to 3–4 times daily. Usual total daily dose 24mg. Maximum total daily dose 36mg.

Notes

  • Not licensed for use in children.

  • Usually prescribed and titrated by neurologists.

  • Timing and frequency of dosing are individual to the specific patient, as maximal effect is seen after 2–3h and is short-lived.

  • Use with caution in liver disease; monitor liver function regularly.

  • Use with caution with drugs known to prolong the QT interval.

  • Avoid abrupt withdrawal—risk of rebound hypertension and tachycardia.

  • Tizanidine plasma concentrations are increased by CYP1A2 inhibitors, potentially leading to severe hypotension.

  • Drowsiness, weakness, and dry mouth are common side effects.

  • Tablets may be crushed and administered in water, if preferred. May be administered via an enteral feeding tube. Tablets do not disperse readily but will disintegrate if shaken in 10mL of water for 5min. The resulting dispersion will flush via an 8Fr NG tube, without blockage.

  • Available as: tablets (2mg, 4mg).

Tramadol

The WHO now advises there is insufficient evidence to make a recommendation for an alternative to codeine (tramadol) and recommends moving directly from non-opioids (step 1) to low-dose strong opioids for the management of moderate uncontrolled pain in children.

Uses

  • Minor opioid with additional non-opioid analgesic actions.

Dose and routes

By mouth

  • Child 5–12 years: 1–2mg/kg every 4–6h (maximum initial single dose of 50mg; maximum of four doses in 24h). Increase, if necessary, to a maximum dose of 3mg/kg (maximum single dose 100mg) every 6h.

  • Child 12–18 years: initial dose of 50mg every 4–6h. Increase, if necessary, to a maximum of 400mg/day, given in divided doses every 4–6h.

By intravenous injection or infusion

  • Child 5–12 years: 1–2mg/kg every 4–6h (maximum initial single dose of 50mg; maximum four doses in 24h). Increase, if necessary, to a maximum dose of 3mg/kg (maximum single dose 100mg) every 6h.

  • Child 12–18 years: initial dose of 50mg every 4–6h. Dose may be increased, if necessary, to 100mg every 4–6h. Maximum 600mg/day in divided doses.

Notes

  • Not licensed for use in children <12 years.

  • Tramadol is a Schedule 3 CD, but exempted from safe custody requirements.

  • By mouth, tramadol is about one-tenth as potent as morphine.

  • Onset of action after an oral dose is 30–60min. Duration of action is 4–9h.

  • Causes less constipation and respiratory depression than the equivalent morphine dose.

  • Analgesic effect is reduced by ondansetron.

  • Soluble or orodispersible tablets may be dissolved in water for administration via an enteral feeding tube.

  • Available as: capsules (50mg, 100mg), soluble tablets (50mg), orodispersible tablets (50mg), modified-release tablets and capsules (100mg, 150mg, 200mg, 300mg, 400mg), oral drops (100mg/mL), and injection (50mg/mL).

Tranexamic acid

Uses

  • Oozing of blood (e.g. from mucous membranes/capillaries), particularly when due to low or dysfunctional platelets.

  • Menorrhagia.

Dose and routes

By mouth

Inhibition of fibrinolysis

  • Child 1 month to 18 years: 15–25mg/kg (maximum 1.5 g) 2–3 times daily.

Menorrhagia

  • Child 12–18 years: 1g tds for up to 4 days. If very heavy bleeding, a maximum daily dose of 4g (in divided doses) may be used. Treatment should not be initiated until menstruation has started.

By intravenous injection over at least 10min

Inhibition of fibrinolysis

  • Child 1 month to 18 years: 10mg/kg (maximum 1g) 2–3 times a day.

By continuous intravenous infusion

Inhibition of fibrinolysis

  • Child 1 month to 18 years: 45mg/kg over 24h.

Mouthwash 5% solution

  • Child 6–18 years: 5–10mL qds for 2 days. Not to be swallowed.

Topical treatment

  • Apply gauze soaked in 100mg/mL of injection solution to the affected area.

Notes

  • Injection not licensed for use in children under 1 year or for administration by iv infusion.

  • Can cause clot ‘colic’ if used in presence of haematuria.

  • Parenteral preparation can be used topically.

  • Available as: tablets (500mg), syrup (500mg/5mL available from ‘specials’ manufacturers), and injection (100mg/mL 5mL ampoules). Mouthwash only as extemporaneous preparation.

Trihexyphenidyl

Uses

  • Dystonias; sialorrhoea (drooling); antispasmodic.

Dose and routes

Oral

  • Child 3 months to 18 years: initial dose of 1–2mg daily in 1–2 divided doses, increased every 3–7 days by 1mg daily; adjusted according to response and side effects; maximum 2mg/kg/daily (maximum 70mg/daily).

Generally, the doses needed to control drooling are much lower than those needed for dystonias.

Notes

  • Anticholinergic agent thought to act through partially blocking central (striatal) cholinergic receptors.

  • Not licensed for use in children.

  • Use in conjunction with careful observation and a full non-drug management programme, including positioning, massage, holding, distraction, checking for causes of exacerbations, etc. Advisable to seek specialist neurological input before use of trihexyphenidyl.

  • Side effects are very common, and it is important to start at a low dose and increase gradually to minimize the incidence and severity. Mouth dryness, gastrointestinal disturbance, blurring of vision, dizziness, and nausea can occur in 30–50% patients. Less common side effects include urinary retention, tachycardia, and, with very high doses, CNS disturbance.

  • Use with caution in children with renal or hepatic impairment.

  • Onset of action is usually within 1h; maximum effect occurs within 2–3h, and duration of effect ~6–12h.

  • May take several weeks for maximal effect on dystonic movements to be seen.

  • Do not withdraw abruptly in children who have been on long-term treatment.

  • Tablets may be crushed and mixed in soft food.

  • For administration via a gastrostomy, the liquid may be used or the tablets will disperse readily in water.

  • Available as: tablets (2mg and 5mg) and oral liquid (pink syrup; 5mg in 5mL).

Vitamin K (phytomenadione)

Uses

  • Treatment of haemorrhage associated with vitamin K deficiency (seek specialist advice).

Dose and routes

By mouth or intravenous

  • Neonate: 100 micrograms/kg.

  • Child 1 month to 18 years: 250–300 micrograms/kg (maximum 10mg) as a single dose.

Notes

  • Caution with iv use in premature infants <2.5kg.

  • Available as Konakion® MM injection 10mg/mL (1mL ampoule) for slow iv injection or iv infusion in 5% glucose; NOT for im injection.

  • Available as Konakion® MM Paediatric 10mg/mL (0.2mL ampoule) for po administration or im injection. Also for slow iv injection or iv infusion in 5% glucose.

  • There is not a UK licensed formulation of vitamin K tablets currently available. Possible to obtain 10mg phytomenadione tablets via a specialist importation company.