Educational only — not medical advice. If you’re in crisis or thinking about suicide: call or text 988 (U.S.) or your local emergency number. Support resources. Under construction and review—see the updates log.

promethazine

Adjunctive therapy

Brand: PHENERGAN

Published 2026-02-15 · Last reviewed 2026-02-22 · 4 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: Dosing is indication-dependent (allergy vs nausea vs motion sickness vs sedation). Labels emphasize using the smallest dose adequate to relieve symptoms (label).·Half-life: Plasma half-life reported ~9–16 h after IV administration; mean ~9.8±3.4 h after IM administration (label).·LAI available: No

Class: Adjunctive therapy
Typical dose: Dosing is indication-dependent (allergy vs nausea vs motion sickness vs sedation). Labels emphasize using the smallest dose adequate to relieve symptoms (label).
Half-life: Plasma half-life reported ~9–16 h after IV administration; mean ~9.8±3.4 h after IM administration (label).
LAI available: No

Quick answers

What is promethazine?: Promethazine (brand Phenergan) is a sedating first-generation antihistamine and phenothiazine derivative used for allergy symptoms, nausea/vomiting, motion sickness, and sedation (label).
What is PHENERGAN?: PHENERGAN is a brand name for promethazine.
What is PHENERGAN (promethazine) used for?: Label indications include: Allergy symptoms, nausea/vomiting, motion sickness, and sedation (label; product-dependent).
What drug class is PHENERGAN (promethazine)?: Antihistamine.
What is the mechanism of action of PHENERGAN (promethazine)?: Sedating first-generation antihistamine (H1 antagonist) and phenothiazine derivative with anticholinergic/antiemetic properties; used for allergy symptoms, nausea, motion sickness, and sedation.
What strengths does PHENERGAN (promethazine) come in?: Oral tablets: 12.5 mg, 25 mg, 50 mg (label).

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).

Boxed 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.

U.S. approvals

Allergy symptoms, nausea/vomiting, motion sickness, and sedation (product-dependent)

Formulations & strengths

Oral tablets: 12.5 mg, 25 mg, 50 mg (label).

Generic availability

Widely available generically.

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.

View labelExact

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 & pharmacokinetics

Plasma half-life reported ~9–16 h after IV administration; mean ~9.8±3.4 h after IM administration (label).
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 & 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

FDA boxed warnings

Promethazine should not be used in children under 2 years because of the potential for fatal respiratory depression (boxed warning).
Injectable promethazine can cause severe chemical irritation and tissue damage (including gangrene); avoid subcutaneous or intra-arterial administration and use extreme caution if IV administration is necessary (boxed warning).

Common side effects (≥10%)

Sedation / impaired alertness: Prominent and sometimes desired; counsel about driving and falls and avoid combining with other sedatives when possible (label/class).
Anticholinergic effects: Dry mouth, constipation, urinary retention, and blurred vision; higher risk in older adults and polypharmacy (Beers/clinical).
Dizziness / orthostasis: Can contribute to falls; reassess in older adults and in patients on antihypertensives.
Confusion / delirium: Anticholinergic delirium can occur, especially in older adults; Beers Criteria generally supports avoiding chronic use when possible (Beers).

Other notable effects

Extrapyramidal symptoms (dystonia, akathisia) can occur because of antidopaminergic activity; rare severe reactions such as NMS are described with phenothiazines (label/class).
Paradoxical agitation and nightmares have been reported, especially in children and older adults (label).
Overdose can cause profound CNS depression, hypotension, respiratory depression, and seizures; keep out of reach of children (label/class).

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

Related hubs:SMI toolkit·Support resources