Promethazine is a versatile phenothiazine-derivative medication widely utilized in clinical practice for its potent antihistaminic, antiemetic, and sedative properties. It functions primarily by antagonizing histamine H1 receptors and exerting central antidopaminergic effects, making it a cornerstone therapy for managing allergic conditions, preventing and treating nausea and vomiting, and serving as an adjunct for sedation. Available in oral tablets, syrups, suppositories, and injectable forms, it offers flexible administration 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, rectal suppositories, injectable solution
• Onset of action: Oral—approximately 20 minutes; IV/IM—rapid onset
• Duration of effect: 4 to 6 hours, though sedation may persist longer
• Metabolism: Hepatic, primarily via CYP2D6
• Excretion: Renal

Benefits

• Provides rapid and effective relief from symptoms of allergic reactions, including urticaria, rhinitis, and conjunctivitis
• Effectively prevents and treats nausea and vomiting associated with motion sickness, surgery, or illness
• Offers sedative effects beneficial for preoperative preparation or as a sleep aid in specific short-term scenarios
• Demonstrates adjunctive utility in managing symptoms of vertigo and migraine
• Available in multiple formulations allowing for tailored administration based on patient age, condition, and preference
• Cost-effective compared to many newer antiemetic or sedative agents

Common use

Promethazine is commonly prescribed for the management of allergic conditions such as seasonal or perennial allergic rhinitis, allergic conjunctivitis, and mild allergic skin reactions. It is also extensively used for the prevention and treatment of nausea and vomiting, particularly in contexts of motion sickness, postoperative recovery, or gastroenteritis. Additionally, it serves as a sedative for preoperative anxiety or short-term insomnia management. Off-label uses sometimes include adjunct treatment for migraine headaches and as an antiemetic in chemotherapy protocols, though other agents are often preferred in oncology settings due to side effect profiles.

Dosage and direction

Dosage must be individualized based on indication, patient age, and route of administration. For adults with allergies or nausea, the typical oral or rectal dose is 25 mg before bedtime or 12.5 mg before meals and at bedtime. Doses may be adjusted up to 50 mg if necessary. For sedation, adults may receive 25–50 mg orally, rectally, or via intramuscular injection preoperatively. Pediatric dosing must be carefully calculated by weight and age, generally starting at 0.25–0.5 mg/kg per dose, not to exceed 25 mg for children under 2 years, and only under strict medical supervision. Always administer with food or milk to minimize gastrointestinal upset. Do not administer intravenously without proper dilution and slow infusion due to risk of severe tissue injury.

Precautions

Use with caution in patients with respiratory conditions such as asthma, chronic obstructive pulmonary disease, or sleep apnea due to potential suppression of cough reflex and respiratory depression. Elderly patients are at increased risk of sedation, confusion, and anticholinergic effects such as dry mouth, constipation, or urinary retention. Avoid activities requiring mental alertness, such as driving or operating machinery, until response to the drug is known. May cause orthostatic hypotension; advise patients to rise slowly from sitting or lying positions. Use during pregnancy only if clearly needed and under medical supervision; it is excreted in breast milk. Not recommended for children under 2 years due to potential for fatal respiratory depression.

Contraindications

Promethazine is contraindicated in individuals with known hypersensitivity to promethazine, other phenothiazines, or any component of the formulation. It must not be used in comatose patients or those with significantly depressed levels of consciousness. Contraindicated in patients with narrow-angle glaucoma, bladder neck obstruction, or prostatic hypertrophy due to anticholinergic effects. Avoid use in patients with severe hepatic impairment. Do not administer subcutaneously or intra-arterially. Concomitant use with monoamine oxidase inhibitors (MAOIs) is contraindicated.

Possible side effect

Common side effects include drowsiness, dizziness, dry mouth, blurred vision, and constipation. Less frequently, patients may experience confusion, tinnitus, photosensitivity, or hypotension. Serious side effects, though rare, can include neuroleptic malignant syndrome, agranulocytosis, seizures, extrapyramidal symptoms such as dystonia or tardive dyskinesia, and severe respiratory depression, especially in children or the elderly. Allergic reactions such as rash, urticaria, or anaphylaxis may occur. Injection site reactions, including tissue necrosis, can happen with improper IV administration.

Drug interaction

Promethazine may potentiate the effects of CNS depressants including alcohol, barbiturates, benzodiazepines, and opioids, increasing risks of sedation and respiratory depression. Concurrent use with anticholinergic drugs may enhance dry mouth, blurred vision, and urinary retention. It may antagonize the effects of dopamine agonists and levodopa. MAOIs can intensify anticholinergic and sedative effects. Caution is advised with drugs that prolong QT interval, such as certain antiarrhythmics or antibiotics. It may interfere with the metabolism of drugs processed by CYP2D6.

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, as this increases the risk of adverse effects.

Overdose

Overdose of promethazine can lead to severe CNS depression, respiratory failure, hypotension, seizures, coma, and in extreme cases, death. Anticholinergic symptoms such as dry mouth, fixed dilated pupils, flushing, and gastrointestinal hypomotility may be prominent. Treatment is supportive and symptomatic, including securing airway, administering activated charcoal if ingestion was recent, and managing hypotension with IV fluids. There is no specific antidote; avoid stimulants which may precipitate seizures. Hemodialysis is not effective.

Storage

Store at room temperature between 15–30°C (59–86°F), away from light, moisture, and heat. Keep oral formulations tightly closed. Do not freeze the syrup or injectable solution. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Properly discard any unused or expired medication as per local guidelines to prevent accidental ingestion or environmental contamination.

Disclaimer

This information is intended for educational purposes and does not constitute medical advice. Always consult a qualified healthcare professional for diagnosis, treatment decisions, and personalized dosage recommendations. Do not initiate, adjust, or discontinue promethazine or any medication without professional guidance. The manufacturer and provider of this information are not liable for any adverse outcomes resulting from the use or misuse of this content.

Reviews

Clinical studies and patient reports generally affirm promethazine’s efficacy in managing allergies, nausea, and providing sedation, particularly appreciating its rapid onset and cost-effectiveness. However, reviews frequently note the significant sedative effect as a drawback for daytime use. Medical professionals emphasize its value in controlled settings but caution against overuse or use in vulnerable populations due to side effect risks. Overall, it remains a well-regarded option within its indicated uses when prescribed judiciously.