Promethazine is a versatile phenothiazine-derivative medication with potent antihistaminic, antiemetic, and sedative properties. It is widely utilized in clinical practice for managing allergic conditions, preventing and treating nausea and vomiting, and serving as a sedative adjunct in perioperative settings. Its mechanism primarily involves antagonism of histamine H1 receptors, though it also exhibits anticholinergic and central dopamine D2 receptor blockade, contributing to its broad therapeutic profile. Available in oral, rectal, and injectable formulations, promethazine offers flexible administration routes tailored to patient needs and clinical scenarios.

Features

• Chemical class: Phenothiazine derivative
• Primary mechanism: Histamine H1 receptor antagonist
• Secondary actions: Anticholinergic and antidopaminergic effects
• Available formulations: Tablets, syrup, suppositories, injectable solution
• Onset of action: Oral—20 minutes; IV—3–5 minutes
• Duration of effect: 4–6 hours for allergic symptoms; 6–12 hours for sedation
• Metabolism: Hepatic, primarily via CYP2D6
• Excretion: Renal

Benefits

• Provides rapid relief from symptoms of allergic reactions, including urticaria, rhinorrhea, and pruritus
• Effectively prevents and treats nausea and vomiting associated with motion sickness, surgery, or illness
• Offers sedative effects useful for preoperative preparation and anxiety reduction
• Demonstrates anti-motion sickness properties through central nervous system depression
• Serves as an adjunctive therapy for anaphylactic reactions alongside epinephrine
• Available in multiple formulations to accommodate various patient populations and clinical needs

Common use

Promethazine is indicated for the management of allergic conditions such as allergic rhinitis, urticaria, and angioedema. It is also approved for the prevention and treatment of nausea and vomiting, including motion sickness and postoperative emesis. Additionally, it is utilized for its sedative effects in preoperative settings, as an adjunct to analgesics for postoperative pain management, and occasionally for nighttime sedation. Off-label uses may include management of migraine-associated nausea and as an antiemetic in chemotherapy protocols, though evidence for latter use is limited compared to newer agents.

Dosage and direction

Dosage must be individualized based on indication, patient age, and route of administration. For adults with allergies or motion sickness: 25 mg orally at bedtime or 12.5 mg before meals and at bedtime. For nausea/vomiting: 12.5–25 mg every 4–6 hours as needed. Rectal suppositories: 12.5–25 mg every 4–6 hours. IM/IV administration (deep IM or slow IV infusion only): 12.5–25 mg every 4–6 hours. For pediatric patients (≥2 years): 0.25–0.5 mg/kg/dose every 4–6 hours, not to exceed 25 mg. Avoid IV push due to risk of severe tissue injury; administer IV doses diluted at concentration ≤25 mg/mL over 10–15 minutes. Do not administer arterially.

Precautions

Use with caution in patients with respiratory depression, asthma, sleep apnea, or COPD due to potential for respiratory suppression. Monitor for signs of neuroleptic malignant syndrome (NMS), particularly with high doses or prolonged use. Risk of drowsiness necessitates caution when operating machinery or driving. May lower seizure threshold; use cautiously in patients with seizure disorders. Elderly patients are more susceptible to anticholinergic effects, orthostatic hypotension, and sedation. Avoid abrupt discontinuation after prolonged use. Use during pregnancy only if clearly needed (Category C). Excreted in breast milk; not recommended during lactation.

Contraindications

Hypersensitivity to promethazine or other phenothiazines. Comatose states or significantly depressed consciousness. Use in children under 2 years due to potential for fatal respiratory depression. Concomitant use with MAO inhibitors (risk of hyperthermia, seizures). Subcutaneous or intra-arterial administration. Known narrow-angle glaucoma. Severe hepatic impairment. Bladder neck obstruction or prostatic hypertrophy. Myasthenia gravis.

Possible side effect

Common: Drowsiness (may diminish with continued use), dizziness, dry mouth, blurred vision, nausea, vomiting. Less common: Extrapyramidal symptoms (dystonia, akathisia), hypotension, tachycardia, photosensitivity, urinary retention. Rare but serious: Neuroleptic malignant syndrome (hyperthermia, muscle rigidity, autonomic instability), agranulocytosis, cholestatic jaundice, seizures, severe respiratory depression, tissue necrosis with improper IV administration. Paradoxical reactions (excitement, nightmares) may occur in children and elderly.

Drug interaction

Potentiates CNS depression with alcohol, barbiturates, opioids, benzodiazepines, and other sedatives. MAO inhibitors may potentiate anticholinergic effects. Antihypertensives may have enhanced hypotensive effects. May antagonize effects of dopamine agonists (levodopa). CYP2D6 inhibitors (fluoxetine, paroxetine) may increase promethazine levels. Anticholinergics may compound urinary retention and dry mouth. Epinephrine effects may be reversed due to alpha-adrenergic blockade.

Missed dose

If a dose is missed, administer as soon as remembered unless it is nearly time for the next dose. Do not double doses to make up for a missed dose. Resume regular dosing schedule. For as-needed use, take when symptoms occur without regard to timing of previous dose.

Overdose

Symptoms: Severe CNS depression (coma, respiratory depression), hypotension, tachycardia, extrapyramidal symptoms, seizures, anticholinergic crisis (hyperthermia, flushed skin). Treatment is supportive: maintain airway, administer activated charcoal if recent ingestion, treat hypotension with IV fluids and vasopressors, control seizures with benzodiazepines. Avoid epinephrine for hypotension due to paradoxical effect. Dialysis not effective. Consider physostigmine for central anticholinergic syndrome.

Storage

Store at 20–25°C (68–77°F). Protect from light. Keep oral formulations tightly closed. Do not freeze. Keep all medications out of reach of children. Discard unused portion of injectable solution after opening. Do not use discolored solutions or tablets.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Always consult a healthcare professional for diagnosis and treatment decisions. Dosage and indications may vary based on individual patient factors and current medical guidelines. Never self-medicate or adjust dosage without medical supervision.

Reviews

“Promethazine remains a valuable agent in our emergency department for allergic reactions and nausea. Its sedative properties are particularly useful for agitated patients. However, we strictly adhere to proper IV administration protocols to avoid tissue injury.” – Emergency Physician, 12 years experience

“While effective, the sedative effects can be pronounced, especially in elderly patients. I reserve it for cases where sedation is desirable and monitor closely for orthostatic hypotension.” – Geriatric Specialist

“For pediatric motion sickness, it’s effective but we use the lowest possible dose and caution parents about drowsiness. Avoid under age 2 per black box warning.” – Pediatrician