promethazine

General Information

Promethazine (brand Phenergan) is a sedating first-generation antihistamine and phenothiazine derivative used for allergy symptoms, nausea/vomiting, motion sickness, and sedation (label).

It is strongly Anticholinergic and sedating. Those effects can be useful for short-term symptom relief, but they also increase constipation, urinary retention, delirium, and falls risk—especially in older adults and in polypharmacy (Beers/clinical).

Black box warning: promethazine should not be used in children under 2 years because of the potential for fatal respiratory depression; caution is emphasized in older children as well, particularly with other respiratory depressants (label).

In psychiatric practice, promethazine is sometimes encountered as a sedating adjunct, but because of anticholinergic burden and CNS/respiratory depression risk it is not a preferred long-term hypnotic strategy.

The promethazine compare view, evidence feed, and print page can support side-by-side review of sedating antihistamines and safer alternatives.

Promethazine is effective for several labeled indications, but its strong anticholinergic and sedating profile can be problematic in serious mental illness where polypharmacy, falls risk, and cognitive vulnerability are common. Beers Criteria guidance supports avoiding chronic first-generation antihistamines in older adults when possible.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

H1 receptor antagonism produces antihistamine effects and sedation.

Antimuscarinic (anticholinergic) activity contributes to dry mouth, constipation, urinary retention, blurred vision, and delirium risk.

Promethazine is a phenothiazine derivative with antidopaminergic properties; extrapyramidal symptoms can occur, especially at higher doses or in susceptible patients (class/StatPearls).

• H1 receptor antagonist (sedation).
• Antimuscarinic (anticholinergic) activity.
• Dopamine receptor antagonism (phenothiazine derivative; EPS risk).

Metabolism and Pharmacokinetics

• Oral onset is about 20 minutes; effects typically last 4–6 hours (up to 12 hours) (label).
• Extensively metabolized hepatically; metabolites are excreted in urine (label).
• Pharmacokinetic studies describe oral and IV disposition in adults; dosing is individualized to indication and tolerability (promethazine PK study).

Dosing and Administration

• Dosing is indication-dependent (allergy vs nausea vs motion sickness vs sedation). Labels emphasize using the smallest dose adequate to relieve symptoms (label).
• Sedation labeling includes bedtime dosing (e.g., 25–50 mg in adults, product-dependent). Next-day impairment can occur; avoid stacking with other sedatives when possible (label/class).
• Promethazine is contraindicated in children under 2 years. In older children and adolescents, avoid use for vomiting of unknown etiology and use caution with respiratory depressants (label).

Monitoring & Labs

• Sedation and next-day impairment (driving safety, falls risk).
• Respiratory depression risk when combined with other depressants or in sleep apnea.
• Anticholinergic effects (constipation, urinary retention, blurred vision) and delirium risk.
• Abnormal movements or rigidity/fever suggesting EPS or rare NMS.

Adverse Effects

Interactions

• Additive CNS/respiratory depression with alcohol, opioids, benzodiazepines, sedating antipsychotics, and other hypnotics; avoid combinations when possible (label/class).
• Additive anticholinergic burden with tricyclic antidepressants, low-potency antipsychotics, and bladder antimuscarinics increases delirium and urinary retention risk (clinical).

Other Useful Information

• Promethazine is often best reserved for labeled uses rather than as a default insomnia medication. If sleep is the main complaint, prioritize CBT-I and consider evidence-backed insomnia options (e.g., DORAs, ramelteon, low-dose doxepin).
• In older adults and high-fall-risk patients, consider alternatives with lower anticholinergic burden when feasible (Beers).
• Document indication, duration, and a stop plan to reduce refill momentum and inadvertent long-term use.

References

1. Promethazine hydrochloride tablets prescribing information — DailyMed (2025)
2. 2023 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults — Journal of the American Geriatrics Society (2023)
3. Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man — British Journal of Clinical Pharmacology (1983)
4. Promethazine (StatPearls) — StatPearls Publishing (NCBI Bookshelf) (2025)