Promethazine is a versatile phenothiazine-derivative medication with potent antihistaminic, antiemetic, and sedative properties. It is widely utilized in clinical practice for managing a range of conditions, from allergic reactions and motion sickness to postoperative nausea and adjunctive sedation. Its efficacy stems from its ability to antagonize histamine H1 receptors, suppress the chemoreceptor trigger zone, and exert anticholinergic and central nervous system depressant effects. This comprehensive profile makes it a valuable tool in both acute and prophylactic therapeutic regimens.

Features

• Chemical class: Phenothiazine derivative
• Primary mechanism: Histamine H1-receptor antagonist
• Secondary actions: Anticholinergic, antiemetic, and sedative effects
• Available forms: Oral tablets, syrup, rectal suppositories, and injectable solutions
• Onset of action: Oral—20 minutes; IV—3–5 minutes; duration up to 12 hours
• Metabolism: Hepatic, primarily via CYP2D6
• Excretion: Renal

Benefits

• Provides rapid and effective 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 adjunctive anxiety management
• Demonstrates utility as an adjunct therapy for migraine headaches and vertigo
• Available in multiple formulations allowing for flexible administration based on clinical need and patient tolerance
• Cost-effective and widely accessible within numerous healthcare systems

Common use

Promethazine is commonly prescribed for the management of allergic conditions such as hay fever, allergic conjunctivitis, and urticaria. It is also indicated for the prevention and treatment of nausea and vomiting, including that related to motion sickness, postoperative recovery, or gastroenteritis. Off-label uses include sedation for agitated patients, adjunct treatment for migraine headaches, and management of vertigo. Its antiemetic and sedative properties make it particularly useful in pediatric, adult, and geriatric populations, though dosing must be carefully adjusted based on age and renal/hepatic function.

Dosage and direction

Dosage varies by indication, formulation, and patient factors. For allergies: Adults—12.5–25 mg orally at bedtime or every 4–6 hours as needed; Children ≥2 years—0.1 mg/kg/dose every 6 hours. For nausea/vomiting: Adults—12.5–25 mg every 4–6 hours; may be administered orally, rectally, or IM/IV. For sedation: Adults—25–50 mg orally/IM/IV. Maximum daily dose for adults is typically 100 mg. Avoid intravenous push; administer diluted IV solution slowly over 10–15 minutes to minimize risk of tissue injury or severe adverse reactions. Dosage reduction is recommended in elderly patients and those with hepatic or renal impairment.

Precautions

Promethazine may cause drowsiness, impaired alertness, or blurred vision; patients should avoid driving or operating machinery until response is known. Use with caution in patients with respiratory conditions (e.g., asthma, COPD), cardiovascular disease, narrow-angle glaucoma, prostatic hypertrophy, or seizure disorders. May mask symptoms of underlying conditions such as intestinal obstruction or brain tumor. Avoid alcohol and other CNS depressants. Elderly patients are at increased risk for anticholinergic effects, confusion, and falls. Not recommended for children under 2 years due to risk of respiratory depression.

Contraindications

Promethazine is contraindicated in individuals with known hypersensitivity to promethazine or other phenothiazines. It should not be used in comatose states, patients with severe CNS depression, or those with suspected or established subcortical brain damage. Contraindicated in neonates and premature infants. Avoid use in patients with bone marrow suppression, severe hepatic impairment, or those concurrently using monoamine oxidase inhibitors (MAOIs). Do not administer via intra-arterial injection due to risk of severe arteriospasm and tissue necrosis.

Possible side effect

Common side effects include drowsiness, dry mouth, blurred vision, dizziness, and tinnitus. Less frequently, patients may experience hypotension, tachycardia, extrapyramidal symptoms (e.g., dystonia, akathisia), or paradoxical excitation (especially in children or elderly). Rare but serious adverse effects include neuroleptic malignant syndrome, agranulocytosis, seizures, and severe respiratory depression. Injection site reactions (pain, necrosis) may occur with improper IM/IV administration. Allergic reactions including rash and photosensitivity are possible.

Drug interaction

Promethazine may potentiate the effects of CNS depressants including opioids, benzodiazepines, sedative-hypnotics, and alcohol. Concurrent use with anticholinergics may increase the risk of adverse effects such as dry mouth, urinary retention, and confusion. May enhance the hypotensive effects of antihypertensives. CYP2D6 inhibitors (e.g., fluoxetine, quinidine) may increase promethazine levels. Avoid concomitant use with MAOIs due to risk of hypertensive crisis or serotonin syndrome. May interfere with the diagnostic accuracy of pregnancy tests, skin allergy testing, or metyrapone tests.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. In that case, skip the missed dose and resume the regular dosing schedule. Do not double the dose to make up for a missed one. For as-needed use, this guidance may not apply; patients should take the next dose when symptoms recur, adhering to recommended minimum dosing intervals.

Overdose

Overdose may manifest as severe CNS depression (ranging from drowsiness to coma), hypotension, respiratory depression, anticholinergic symptoms (e.g., dry mouth, fixed dilated pupils, hyperthermia), agitation, hallucinations, or convulsions. Cardiovascular collapse may occur in severe cases. Treatment is supportive and symptomatic: maintain airway, assist ventilation if needed, administer activated charcoal if ingestion was recent, and manage hypotension with IV fluids or vasopressors. Avoid stimulants; benzodiazepines may be used for seizures. There is no specific antidote.

Storage

Store at controlled room temperature (20–25°C or 68–77°F). Protect from light and moisture. Keep oral and rectal formulations in their original container, tightly closed. Do not freeze liquid formulations. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Discard any discolored or precipitated injectable solutions.

Disclaimer

This information is intended for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before starting, changing, or stopping any medication. Dosage and indications may vary based on individual patient factors, regional guidelines, and updated clinical evidence. The prescriber is responsible for evaluating risks and benefits specific to the patient.

Reviews

Clinical experience and studies support promethazine’s efficacy in managing allergic symptoms and nausea, with particular praise for its rapid onset and flexible administration routes. However, sedation and anticholinergic side effects are frequently noted drawbacks. Many clinicians value its role in palliative and perioperative care, though caution is emphasized regarding its use in pediatric and elderly populations due to safety concerns. Overall, it remains a well-regarded option within its therapeutic class when used judiciously.