Drug reference

Promethazine

Atypical Antipsychotic · Antihistamine, Antiemetic, Sedative

Also known as Promethazine Hydrochloride, Phenergan, Avomine

Atypical AntipsychoticAntihistamine, Antiemetic, SedativeATC R06AD02

CDSCO approvedSchedule HJan AushadhiATC R06AD02

Pharmacokineticsplasma · t hours

ONSET: 40min · Oral: 20-60 minutes; IM: 20 minutes; IV: 3-5 minutes
PEAK: 2.5h · Oral: 2-3 hours; IM: 30-60 minutes
t½: 12h · 10-14 hours (range 7-19 hours)
DURATION: 5h · 4-6 hours (up to 12 hours for sedative effects)

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

C (Risk cannot be ruled out. Use only if potential benefit justifies potential risk to fetus).

FDA category + note

Top interactionssee all 12 →

AminophyllineContraindicatedTextbookKDT 7e · p227
DiazepamSevereTextbook-citedKDT 7e · p950
Aminolevulinic AcidSevereDatabaseDDInter
AmiodaroneSevereDatabaseDDInter

Mechanism

Promethazine is a first-generation H1 receptor antagonist that competitively blocks histamine at H1 receptors, reducing allergic symptoms. It also possesses significant anticholinergic activity, contributing to its antiemetic and sedative effects, and acts as a weak dopamine receptor antagonist, which may further contribute to its antiemetic properties. Its sedative effects are due to CNS depression.

Indications

Allergic conditions (e.g., rhinitis, conjunctivitis, urticaria)Motion sicknessNausea and vomiting (post-operative, chemotherapy-induced (off-label))Sedation (pre-operative, post-operative, obstetric)Insomnia (short-term, off-label)Adjunct to analgesics for pain relief (off-label)antiallergic actionmotion sickness (prophylactic, milder types)morning sicknessdrug induced vomitingpostoperative vomitingradiation sicknessparkinsonism (mild symptomatic relief in early cases)acute muscle dystoniapreanaesthetic medicationcoughCough in respiratory allergic statesParkinson's disease (mild cases, or combined with levodopa to lower its dose)Drug-induced parkinsonismmorning sickness (in low doses if necessary)chemotherapy induced nausea and vomiting (CINV, in combination)

Dosing

Adult: Allergy: 12.5 mg orally 3-4 times daily or 25 mg orally at bedtime. Motion Sickness: 25 mg orally 30-60 minutes before travel, then 25 mg every 8-12 hours if needed. Nausea/Vomiting: 12.5-25 mg orally/IM/IV every 4-6 hours as needed. Sedation: 25-50 mg orally/IM at bedtime or pre-operatively.
Pediatric: Not recommended for children less than 2 years due to risk of fatal respiratory depression. Children greater than 2 years: Allergy/Sedation: 0.25-0.5 mg/kg orally at bedtime or 2-4 times daily; Max 12.5 mg/dose. Motion Sickness: 0.5 mg/kg orally 30-60 minutes before travel, repeat 8-12 hourly if needed. Nausea/Vomiting: 0.5 mg/kg orally/IM/IV every 4-6 hours as needed; Max 25 mg/dose.
Renal adjustment: Use with caution in severe renal impairment. No specific dose adjustment guidelines; consider lower doses and extended intervals based on clinical response.
Hepatic adjustment: Use with caution in hepatic impairment. Consider dose reduction in severe hepatic dysfunction.
Geriatric: Start with lower doses (e.g., 12.5 mg at bedtime) due to increased sensitivity to anticholinergic effects, sedation, and risk of falls. Avoid in elderly with cognitive impairment.
Max dose: Generally, 100 mg/day for adults; lower doses are often preferred due to significant sedation and anticholinergic side effects.

Pharmacokinetics

Onset

Oral: 20-60 minutes; IM: 20 minutes; IV: 3-5 minutes

Peak effect

Oral: 2-3 hours; IM: 30-60 minutes

Duration

4-6 hours (up to 12 hours for sedative effects)

Half-life

10-14 hours (range 7-19 hours)

Bioavailability

25% (oral due to extensive first-pass metabolism)

Protein binding

80-93%

Metabolism

Extensive hepatic metabolism via hydroxylation and N-demethylation (CYP2D6, CYP2B6)

Excretion

Primarily renal (major metabolites); small amount in feces

Contraindications

Hypersensitivity to promethazine or other phenothiazines
Children less than 2 years due to risk of fatal respiratory depression
Patients in coma or with severe CNS depression
Lower respiratory tract symptoms, including asthma, COPD
Concomitant use with MAO inhibitors (within 14 days)
Narrow-angle glaucoma (relative)
Prostatic hypertrophy (relative)
Bladder neck obstruction (relative)
Stenosing peptic ulcer (relative)
children aged 2 years or less

Side effects

Common

DrowsinessDizzinessBlurred visionDry mouthUrinary retentionConstipationConfusionParadoxical excitation (especially in children)sedationdiminished alertnesslight headednessmotor incoordinationfatiguetendency to fall asleepalteration of bowel movementurinary hesitancyblurring of visionAnticholinergic actions (may reduce secretions)dryness of mouth

Serious

Respiratory depression (especially in children less than 2 years)
Neuroleptic malignant syndrome (rare)
Agranulocytosis (rare)
Seizures (rare)
Severe tissue injury with IV extravasation (requires careful administration)
Extrapyramidal symptoms
Prolongation of QT interval
serious respiratory depression in young children

Pregnancy & lactation

Pregnancy

C (Risk cannot be ruled out. Use only if potential benefit justifies potential risk to fetus).

Lactation

Excreted in breast milk. Not recommended during breastfeeding due to potential for sedation and respiratory depression in infants, especially neonates, and potential reduction in milk supply due to anticholinergic effects.