Promethazine is a first-generation phenothiazine derivative with potent antihistaminic (H1-receptor antagonist), antiemetic, sedative, anticholinergic, and local anesthetic properties. It is widely used in India for symptomatic relief of allergic conditions, motion sickness, and as a pre-operative sedative. Its sedative effects are pronounced, making it a common choice for managing insomnia and anxiety in certain clinical contexts, though its use is tempered by significant CNS and anticholinergic side effects.
Adult: Allergy/Nausea/Sedation: 25 mg at bedtime or 12.5 mg before meals and at bedtime. Can be given 6.25-12.5 mg TID for allergy. Motion Sickness: 25 mg taken 30-60 minutes before travel, repeat after 8-12 hours if needed. Pre-op Sedation: 25-50 mg night before surgery or 50 mg 1 hour before procedure.
Note: Take with food or milk to minimize GI upset. Tablet should be swallowed whole with a full glass of water. For motion sickness, take at least 30 minutes before travel. Avoid crushing or chewing. Do not take with alcohol. For IM use: Inject deep into a large muscle mass to avoid tissue necrosis.
Promethazine competitively and reversibly blocks postsynaptic histamine H1-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Its central antiemetic and sedative effects are mediated through antagonism of central H1-receptors and muscarinic receptors in the chemoreceptor trigger zone (CTZ) and vomiting center. It also possesses significant anticholinergic (antimuscarinic) and weak dopaminergic blocking activity.
Pregnancy: Category C (US FDA). Animal studies show risk; human data inadequate. Use only if potential benefit justifies potential fetal risk. Avoid near term due to possible neonatal adverse effects (respiratory depression, extrapyramidal symptoms).
Driving: STRONGLY DISCOURAGED. Causes significant drowsiness and impairs cognitive and motor functions. Patients should not drive or operate heavy machinery for at least 6-8 hours after a dose, or longer if affected.
| CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Potentiated sedation, respiratory depression, impaired psychomotor performance. | Major |
| MAO Inhibitors (Phenelzine, Tranylcypromine) | Increased anticholinergic effects, hyperthermia, severe hypotension. | Contraindicated |
| Anticholinergics (Atropine, Tricyclic Antidepressants) | Additive anticholinergic side effects (dry mouth, urinary retention, confusion). | Major |
| QT-prolonging drugs (Erythromycin, Fluoroquinolones, Antiarrhythmics) | Increased risk of Torsades de Pointes. | Major |
| Epinephrine | Promethazine's alpha-blockade may reverse epinephrine's vasopressor effect, leading to further hypotension. | Moderate |