Cyclizine

Cyclizine is a piperazine H1 antihistamine with antimuscarinic activity that acts on the vomiting centre and vestibular pathways. It is widely used in postoperative nausea, opioid-induced nausea, vertigo and palliative care, but it can reduce cardiac output in severe heart failure and has misuse potential.

Classification. H1 antihistamine antiemetic; antimuscarinic.

Mechanism. Blocks H1 and muscarinic M1 receptors in the vomiting centre, vestibular nuclei and nucleus tractus solitarius, and reduces vestibular input to the vomiting centre. It also has a weak effect on the lower oesophageal sphincter.

Pharmacodynamics. Onset: oral about 30 minutes; IM and IV about 15 to 30 minutes. Duration 4 to 6 hours. Mild haemodynamic effects can raise heart rate and lower stroke volume.

Pharmacokinetics. Oral bioavailability about 70%. Half-life about 20 hours. Metabolised in the liver by N-demethylation to norcyclizine (inactive) and excreted in urine.

Adult doses unless stated. Maximum 150 mg daily.

Nausea and vomiting, general.

• 50 mg orally, IM or slow IV up to three times daily (every 8 hours).

• Maximum 150 mg in 24 hours.

Postoperative nausea and vomiting. 50 mg IM or slow IV at the end of surgery, then 50 mg every 8 hours as needed.

Opioid-induced nausea. 50 mg orally or IM up to three times daily, in addition to regular analgesia; review the opioid dose.

Motion sickness. 50 mg orally 1 to 2 hours before travel, then every 6 to 8 hours as needed, maximum three doses in 24 hours.

Vertigo and labyrinthine disorders. 50 mg orally up to three times daily for the shortest period needed (days, not weeks).

Palliative care nausea (continuous subcutaneous infusion). 100 to 150 mg over 24 hours, diluted with water for injection; maximum 150 mg daily. Cyclizine is first-line for raised intracranial pressure, mechanical bowel obstruction and vestibular causes.

Paediatric dosing.

• Age 6 to 11 years: 25 mg up to three times daily.

• Age 12 to 17 years: adult dose.

• Under 6 years: specialist use only.

Kidney and liver adjustment. No fixed adjustment. Use the lowest dose in severe kidney or liver impairment because of sedation and anticholinergic effects.

Contraindications. Hypersensitivity; severe heart failure (it lowers cardiac output and raises heart rate); acute myocardial infarction. Use with caution in narrow-angle glaucoma, prostatic enlargement and urinary retention, pyloric stenosis, intestinal obstruction (unless used under palliative direction), epilepsy, porphyria and severe liver disease.

Common adverse effects. Drowsiness, dry mouth, blurred vision, headache, constipation and urinary retention.

Serious adverse effects.

• Tachycardia, hypotension and reduced cardiac output with IV use in heart failure or recent infarction.

• Confusion, delirium and hallucinations, particularly in older adults and at high doses.

• Euphoria and dependence with misuse, including injection with opioids.

• Painful IV injection and thrombophlebitis.

• Rare extrapyramidal reactions, hypersensitivity and cholestatic jaundice.

Major interactions.

• Other anticholinergics (tricyclic antidepressants, antihistamines, antipsychotics, hyoscine): additive effects.

• CNS depressants, alcohol and opioids: additive sedation.

• Metoclopramide and domperidone: cyclizine opposes their prokinetic effect.

• MAOIs: avoid.

• Aminoglycosides and other ototoxic drugs: cyclizine may mask early ototoxicity.

• Antimuscarinics reduce the effect on gastric emptying.

Special groups.

• Pregnancy: no consistent harm in available data; used when other antiemetics have failed.

• Breastfeeding: small amounts enter milk; monitor the infant for drowsiness.

• Children: dose by age; avoid under 6 years unless specialist.

• Older adults: increased risk of confusion, urinary retention and falls; use lower doses.

• Kidney impairment: use lowest effective dose.

• Liver impairment: use lowest effective dose; sedation may mask encephalopathy.

• Misuse: check for diversion where injectable supply is uncontrolled.

Formulations. Tablets 50 mg; injection 50 mg in 1 mL (cyclizine lactate).

IV administration.

• Inject 50 mg slowly over 3 to 5 minutes; rapid injection causes pain and tachycardia.

• Flush the line with water for injection before and after.

• Cyclizine precipitates in sodium chloride 0.9% at higher concentrations and in solutions with some other drugs, so use water for injection to dilute in syringe drivers.

Baseline. Cardiac history including heart failure. Review of anticholinergic burden in older adults.

Monitoring.

• Heart rate and blood pressure after IV doses in cardiac patients.

• Sedation, confusion and urinary retention.

• Control of vomiting; review the underlying cause.

Therapeutic drug monitoring. Not applicable.

Stopping. After short use, no taper is needed. After regular use for more than 2 weeks, reduce gradually to limit rebound nausea.

Referral and escalation. Review the diagnosis if vomiting persists after 24 to 48 hours: consider obstruction, raised intracranial pressure, metabolic causes and pregnancy. Stop and reassess in heart failure.