Antihistamine Antiemetics

Antihistamine antiemetics are H1 receptor antagonists with strong muscarinic blocking action. They act on the vestibular nuclei and vomiting centre and are most effective for motion sickness, vestibular disease, and nausea from raised intracranial pressure or opioids.

Pharmacokinetics. Well absorbed orally; hepatic metabolism; duration 4 to 8 hours.

• Cyclizine 50 mg orally, intramuscularly or intravenously up to three times daily; maximum 150 mg daily.
• Promethazine 12.5 to 25 mg every 4 to 6 hours; maximum 100 mg daily.
• Dimenhydrinate 50 to 100 mg every 4 to 6 hours; maximum 400 mg daily.
• Meclizine 12.5 to 25 mg once or twice daily.
• Doxylamine 10 mg with pyridoxine 10 mg, up to four tablets daily.

Differences. Cyclizine is least sedating of the group, but can cause tachycardia and has misuse potential. Promethazine is strongly sedating.

• Motion sickness and vertigo: promethazine or dimenhydrinate before travel.
• Opioid-induced nausea and postoperative nausea: cyclizine.
• Nausea and vomiting from raised intracranial pressure or bowel obstruction: cyclizine.
• Nausea and vomiting of pregnancy: doxylamine with pyridoxine first-line; cyclizine or promethazine second-line.

Selection. Not effective for chemotherapy-induced vomiting alone.

Contraindications. Promethazine under 2 years (respiratory depression); acute asthma attack, narrow-angle glaucoma, urinary retention; severe heart failure or acute myocardial infarction for cyclizine.

Adverse effects. Sedation, dry mouth, blurred vision, urinary retention, constipation, confusion in older adults. Promethazine intravenous injection can cause severe tissue injury, gangrene and thrombophlebitis; use deep intramuscular injection or a dilute slow infusion. QT prolongation with promethazine.

Interactions. Additive sedation with alcohol, opioids and benzodiazepines; additive anticholinergic burden with tricyclic antidepressants and antipsychotics.

Special groups.

• Pregnancy: doxylamine with pyridoxine, cyclizine and promethazine are acceptable.
• Breastfeeding: sedating antihistamines may sedate the infant and reduce milk supply.
• Children: avoid promethazine under 2 years; avoid cyclizine for routine use.
• Older adults: avoid where possible (anticholinergic load, falls, delirium).
• Liver impairment: reduce doses.

Monitoring. Sedation, respiratory rate with opioids, injection site.

Referral and escalation. Vomiting with neurological deficit, headache with raised intracranial pressure, or suspected misuse needs review.