What is the proper dosage and usage of Promethazine (phenothiazine) for adults?

Promethazine Dosing and Usage for Adults

For adults, promethazine is dosed at 12.5-25 mg orally, intravenously (diluted and infused slowly at ≤25 mg/min), or intramuscularly every 4-6 hours as needed, with the FDA-approved maximum single dose of 50 mg for sedation and 25 mg for antiemetic use. 1

Standard Adult Dosing by Indication

Nausea and Vomiting

• Initial dose: 25 mg orally, intravenously, or rectally 1
• May repeat every 4-6 hours as necessary 1
• Lower doses (6.25-12.5 mg IV) are equally effective and cause less sedation than standard 25 mg dosing 2, 3
• For prophylaxis (surgical/postoperative): 25 mg repeated at 4-6 hour intervals 1

Allergies

• 25 mg at bedtime, or 12.5 mg before meals and at bedtime 1
• Alternative: 6.25-12.5 mg three times daily 1
• Adjust to smallest effective dose after initiation 1

Motion Sickness

• 25 mg twice daily 1
• First dose: 30-60 minutes before travel 1
• Second dose: 8-12 hours later if needed 1
• Subsequent days: 25 mg on arising and before evening meal 1

Sedation

• Nighttime sedation: 25-50 mg at bedtime 1
• Preoperative: 50 mg the night before surgery, combined with reduced doses of narcotics/barbiturates and atropine-like drugs 1
• Postoperative: 25-50 mg with appropriately reduced analgesic doses 1

Administration Routes and Critical Safety Considerations

Intravenous Administration (Highest Risk)

• Must dilute and infuse slowly at ≤25 mg/min to minimize hypotension risk 4, 1
• Intramuscular route is preferred per 2023 FDA labeling changes due to limb-threatening complications from extravasation or inadvertent intra-arterial injection 5
• Severe tissue necrosis and gangrene can occur with perivascular extravasation 4

Adjunctive Use in Endoscopy

• 12.5-25 mg IV as adjunct to standard sedation (narcotics/benzodiazepines) 4
• Onset: 5 minutes; Duration: 4-6 hours 4
• May require reduction in standard sedation agent doses 4

Absolute Contraindications and High-Risk Populations

Contraindicated

• Children under 2 years of age due to fatal respiratory depression risk 6, 1
• Concurrent MAOI use 6

Use With Extreme Caution

• Closed-angle glaucoma, prostatic hypertrophy, bladder neck obstruction (anticholinergic effects) 6
• Hyperthyroidism (cardiovascular effects) 6
• Elderly patients (increased ADR risk, consider starting at 6.25 mg) 3
• Renal or hepatic disease (dose reduction recommended) 4

Common Adverse Effects

• Sedation/drowsiness (most common, dose-dependent) 4
• Hypotension (especially with rapid IV administration) 4
• Dizziness, blurred vision, dry mouth 4
• Extrapyramidal effects (restlessness to oculogyric crises) 4
• Respiratory depression (particularly with concurrent CNS depressants) 4
• Neuroleptic malignant syndrome (rare) 4

Key Clinical Pearls

Lower doses are safer and equally effective: Studies demonstrate 6.25 mg IV promethazine provides equivalent antiemetic efficacy to ondansetron 4 mg with similar sedation profiles, while causing significantly fewer adverse reactions than 12.5 mg or 25 mg doses 2, 3

Pregnancy use: European guidelines recommend phenothiazines (including promethazine) as first-line pharmacologic treatment for hyperemesis gravidarum, though metoclopramide has fewer side effects (less drowsiness, dizziness, dystonia) 4

Withdraw immediately if extrapyramidal symptoms develop 4