Medication Overview

Promethazine is a first-generation antihistamine with strong sedative, antiemetic, and anticholinergic properties. It is structurally related to phenothiazines but exhibits only weak dopamine antagonist properties at standard doses.

Pharmacological Class

Belongs to the class of medications known as phenothiazines. Acts primarily as an H1 receptor antagonist, thereby reducing the effects of natural histamine. Exhibits significant anticholinergic and sedative properties as well.

Indications and Usage

Prescribed for the relief of allergic conditions including rhinitis, conjunctivitis, and skin reactions such as urticaria and pruritus. Also used for nausea, vomiting, and motion sickness. Indicated for sedation in preoperative, postoperative, and obstetric settings.

Mechanism of Action

Promethazine works by blocking H1 histamine receptors, thereby preventing histamine from exerting its effects on the cardiovascular system and smooth muscles. Its anticholinergic action contributes to its effectiveness in managing motion sickness and nausea.

Pharmacokinetics

After oral administration, Promethazine is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 3 hours. It is extensively metabolized in the liver and its elimination half-life ranges between 10 to 19 hours.

Dosage and Administration

Adult Dosage

Recommended for allergic conditions in doses of 25 mg before bedtime, or 12.5 mg before meals if needed. For motion sickness, 25 mg taken two hours before travel, followed by subsequent doses every 8 to 12 hours as required.

Pediatric Dosage

In children aged 2 years and older, the dosage is generally adjusted according to body weight and clinical response. Typical doses range from 12.5 to 25 mg, administered one to three times daily.

Geriatric Dosage

Lower doses are often recommended for older adults due to increased risk of adverse reactions, including central nervous system depression and anticholinergic effects. Monitoring for side effects is essential.

Administration Guidelines

Administered orally as tablets or syrup, or by rectal suppositories. Should be taken with or without food. When given intravenously, it must be administered slowly to reduce the risk of severe hypotension and tissue damage.

Contraindications and Precautions

Absolute Contraindications

Contraindicated in patients with hypersensitivity to promethazine or other phenothiazines. Should not be used in pediatric patients less than 2 years of age due to potential respiratory depression. Contraindicated in patients receiving large doses of CNS depressants or who are in a comatose state.

Cautions and Considerations

Caution in patients with severe cardiovascular disease, liver disease, respiratory conditions including asthma, glaucoma, and urinary retention. Monitor for exacerbation of these conditions during treatment.

Interactions with Other Drugs

Central Nervous System Depressants

Concurrent use with CNS depressants such as alcohol, barbiturates, and narcotics may augment sedative effects, increasing risk of respiratory depression. Dose adjustments may be required and close monitoring is essential when co-administering.

Anticholinergic Drugs

Enhanced anticholinergic side effects possible with concomitant use of anticholinergic drugs such as certain antidepressants, antiparkinsonian agents, and atropine. Monitor for symptoms like dry mouth, constipation, urinary retention, and tachycardia.

Monoamine Oxidase Inhibitors

Potential increased risk of severe adverse reactions when given with MAO inhibitors. Avoid concomitant use; allow a minimum of 14 days to elapse between discontinuing an MAO inhibitor and initiating promethazine.

Blood Pressure Medications

May potentiate the effects of antihypertensive drugs, leading to increased risk of hypotension. Monitoring of blood pressure is recommended, and dose adjustments of antihypertensives may be necessary.

Side Effects and Monitoring

Common Side Effects

Includes drowsiness, dizziness, dry mouth, blurred vision, and constipation. These effects are dose-dependent and generally subside with continued treatment.

Severe Side Effects

Severe side effects may include respiratory depression, especially in children under 2 years, and neuroleptic malignant syndrome. Immediate medical attention is required for symptoms such as severe confusion, jaundice, or uncontrolled movements.

Monitoring Parameters

Monitor liver function tests, complete blood count, and renal function during prolonged therapy. Periodically assess for signs of dehydration, particularly in young children and elderly patients.

Special Populations

Pregnancy Considerations

Use during pregnancy only if the potential benefit justifies the risk to the fetus. Limited data exist on use in pregnant women; however, it should be avoided near term due to potential for neonatal respiratory depression and extrapyramidal symptoms.

Lactation Considerations

Promethazine is excreted into breast milk. Use with caution in breastfeeding women due to the potential for adverse effects in the nursing infant. Alternatives may be considered based on clinical necessity.

Pediatric Considerations

Not recommended for use in children under 2 years due to risk of fatal respiratory depression. In older children, dose carefully and monitor for excessive sedation and other adverse reactions.

Geriatric Considerations

Elderly individuals are more sensitive to the side effects of promethazine, including dizziness, sedation, and confusion. Lower initial doses and attentive monitoring are recommended to avoid complications such as falls or cognitive impairment.

Storage and Handling

Storage Conditions

Store at room temperature, between 20-25°C (68-77°F), protected from light and moisture. Ensure the bottle is tightly closed when not in use to maintain potency and prevent contamination.

Handling Precautions

Handle with care and keep out of reach of children. Dispose of any unused medication safely, following local regulations for pharmacy waste to prevent accidental exposure or ingestion.