Promethazine
Promethazine (hydrochloride)
Phenergan, Promethegan (suppositories)
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Summary
Common uses
Allergic conditions (FDA)0, Motion sickness (FDA)0, Nausea and vomiting from various causes (FDA; postoperative, chemotherapy, hyperemesis gravidarum, motion sickness)0, Preoperative sedation (FDA)0, Acute migraine adjunct (off-label)0
Pharmacy
Starting dose
Allergy: 25 mg PO BID-QID. Nausea/vomiting: 12.5-25 mg PO/IM/IV/PR every 4-6 hours. Motion sickness: 25 mg PO 30-60 minutes before travel. Pediatric <2 years: contraindicated
Preparations
Tablets 12.5, 25, 50 mg; oral syrup 6.25 mg/5 mL; suppositories 12.5, 25, 50 mg; injection 25 mg/mL and 50 mg/mL
US FDA Max
100 mg/day (adult)
Pharmacology
Routes
Oral, IM, IV (with caution), rectal
Onset
20 minutes (oral); 5 minutes (IV)
Duration
4-6 hours
Half-life
12-15 hours[1]
Bioavailability
~25% (oral, with extensive first-pass)[1]
Pregnancy
Older agent with substantial use experience, including in hyperemesis gravidarum; broadly reassuring observational data[1]
Legal status
Purported mechanism
Phenothiazine chemistry, sharing the receptor profile with the typical neuroleptics but used at lower doses and primarily for antihistamine and antiemetic effect rather than neuroleptic effect. Strong H1 antihistamine activity, moderate D2 antagonism (the antiemetic mechanism via chemoreceptor trigger zone in the area postrema), moderate muscarinic antagonism, and α1-adrenergic antagonism.0 Extrapyramidal symptoms (acute dystonia, akathisia) can occur at high doses or with chronic use, reflecting the phenothiazine D2 activity. The contraindication in children under 2 years follows fatal respiratory depression reports; the IV caution follows reports of severe tissue necrosis from extravasation despite proper technique[1].