Promethazine is a sedating antihistamine used for intense allergies, nausea/vomiting and occasional insomnia. It is also used before and after surgery to calm patients and prevent vomiting. It can cause significant drowsiness.
Also known as: Fenergan, Phenergan
Promethazine plus midazolam causes additive CNS depression (profound sedation, respiratory depression) and hypotension.
Both depress the CNS through different mechanisms; promethazine also inhibits midazolam metabolism.
Level of consciousness, respiratory rate and saturation.
Extreme drowsiness, slow or shallow breathing.
Avoid the combination outside monitored settings (procedural sedation only with trained team and airway support).
EMC-UK — Phenergan (promethazine) SmPC, CNS depression with benzodiazepines: https://www.medicines.org.uk/emc/product/4941
Lithium can lower the seizure threshold when combined with promethazine; there is also additive sedation risk.
The lithium carbonate label lists antipsychotics and sedatives as drugs that lower the seizure threshold.
Serum lithium, tremor, seizure history.
Tremor, confusion, seizures.
Monitor neurological status; counsel the patient on lithium toxicity signs.
DailyMed — Lithium Carbonate label, seizure threshold: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b839ff4b-f62d-41ab-a823-550a756d58ec
Alcohol potentiates promethazine drowsiness and reduced alertness; sedating antihistamines potentiate alcohol effects (Prontuário 10.1/Annex 6).
Do not drink alcohol while taking promethazine and for hours afterwards.
Prontuário Terapêutico INFARMED, 10.1 (l. 30138); Annex 6 (alcohol — CNS).
Seizures can be precipitated by sedating antihistamines — not recommended in children with epilepsy (Prontuário 10.1).
Avoid in poorly controlled epilepsy; monitor for seizures.
Prontuário Terapêutico INFARMED, 10.1: "Seizures can also be precipitated... children with epilepsy".
Sedating antihistamines are not considered safe in porphyria (Prontuário 10.1 note).
Prefer cetirizine/chlorphenoxamine if antihistamine needed (considered safe).
Prontuário Terapêutico INFARMED, 10.1: "chlorphenoxamine and cetirizine seem safe in porphyria".
Antimuscarinic effects of sedating antihistamines — dry mouth, urinary retention, angle-closure glaucoma (Prontuário 10.1).
Avoid in unoperated angle-closure glaucoma.
Prontuário Terapêutico INFARMED, 10.1 (antimuscarinic effects of antihistamines).
Antihistamines must be used with care in hepatic impairment (Prontuário 10.1/Annex 3).
Reduce dose; monitor for excessive sedation.
Prontuário Terapêutico INFARMED, 10.1: "used with care in hepatic impairment".
Annex 1 classifies promethazine as factor "C or D": extensive experience without established teratogenicity at usual doses; avoid high doses and prolonged use near term due to neonatal depression (promethazine is sedating and newborns are sensitive).
Use as a single dose or short course for nausea/anaphylaxis; avoid chronic use and use near term.
H1 antihistamines in general: "significant amounts of some antihistamines in milk... avoidance recommended: drowsiness" (Annex 2, l. 42199). Promethazine has the most data: small amounts, but monitor infant drowsiness/irritability.
Prontuário Terapêutico INFARMED — Annex 1: "Promethazine — C or D" (l. 41377); Annex 2: Antihistamines H1 (l. 42199). EMC-UK (MHRA) — Promethazine SmPC (Phenergan).
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
First-generation H1 antihistamine with strong sedation and antiemetic action; its safety profile demands age restrictions and care with the injectable route.
Competitive H1 antagonist (blocks histamine bronchoconstriction, pruritus and vasodilation) with additive actions: muscarinic antagonism (dry mouth, mydriasis), central sedation via brain H1 and D2 blockade at the vomiting centre (antiemetic). Prolongs QT at high doses.
Oral: good absorption, peak 2–3 h, onset 20–30 min. IM: rapid (peak 1–2 h); NEVER direct undiluted IV (tissue necrosis, gangrene with arterial extravasation).
Extensive hepatic metabolism (N-demethylation, S-oxidation, aromatic hydroxylation — CYP2D6 and others); renal excretion of metabolites; minimal unchanged fraction. Cirrhosis and the elderly: increased exposure.
10–19 h (adults); prolonged in neonates and infants — the basis of the < 2 years contraindication.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
