What is the recommended dose of promethazine (Phenergan) for nausea and vomiting?

Promethazine Dosing for Nausea and Vomiting

For nausea and vomiting, administer promethazine 12.5-25 mg orally, rectally, or intravenously every 4-6 hours as needed, with lower doses (6.25-12.5 mg) being equally effective and causing significantly less sedation, particularly in elderly patients. 1, 2, 3

Standard Dosing Recommendations

Acute Nausea and Vomiting

• The FDA-approved dose is 25 mg, with 12.5-25 mg doses repeated every 4-6 hours as necessary 3
• The American Gastroenterological Association specifically recommends 12.5-25 mg by mouth or rectally every 4-6 hours during acute episodes of cyclic vomiting syndrome 1, 2
• For prophylaxis of postoperative nausea and vomiting, the standard dose is 25 mg repeated at 4-6 hour intervals 3

Low-Dose Strategy (Preferred for Most Patients)

• Research demonstrates that 6.25-12.5 mg IV promethazine provides equivalent antiemetic efficacy to standard 25 mg doses but with significantly less sedation 4, 5
• Low-dose promethazine (6.25 mg IV) relieves nausea and vomiting as effectively as ondansetron 4 mg IV, with 74% of patients experiencing relief at one hour 5
• The 6.25 mg dose produces significantly fewer adverse drug reactions compared to 12.5 mg in elderly patients (P = 0.048) 4
• Consider starting with 6.25-12.5 mg PO for antiemetic purposes, as these doses are equally effective as standard 25 mg doses but cause significantly less sedation 2

Route-Specific Considerations

Oral Administration (Preferred)

• Standard dose: 12.5-25 mg every 4-6 hours 1, 3
• Oral route is safer than IV administration and should be used whenever possible 2

Rectal Administration

• Dose: 12.5-25 mg suppository every 4-6 hours or 25 mg suppository every 12 hours 1, 3
• Promethazine suppositories are effective for post-discharge nausea and vomiting, with 89% of patients reporting symptom improvement and no adverse effects reported 6

Intravenous Administration (Use with Caution)

• Dose: 12.5-25 mg infused slowly to minimize hypotension risk 2
• Clinical effects are evident within 5 minutes, with duration of action 4-6 hours and plasma half-life 9-16 hours 2
• Avoid IV promethazine when possible due to risks of tissue necrosis, thrombophlebitis, and gangrene; if IV route is necessary, ensure proper IV placement with slow infusion 2, 7

Clinical Context and Special Populations

Chemotherapy-Induced Nausea/Vomiting

• The National Comprehensive Cancer Network recommends 12.5-25 mg PO or IV every 4 hours for breakthrough treatment 2
• Promethazine 25-50 mg per rectum every 6 hours as needed is appropriate for grade 4 emesis potential 1

Pediatric Dosing

• Promethazine is contraindicated in children under 2 years of age due to risk of fatal respiratory depression 2, 3
• For children ≥2 years: usual dose is 0.5 mg per pound of body weight, adjusted to age, weight, and severity of condition 3
• For motion sickness in children: 12.5-25 mg twice daily 3

Elderly Patients

• Start with 6.25 mg IV as this dose is as effective as higher doses with fewer adverse drug reactions 4
• Monitor closely for anticholinergic effects including confusion, urinary retention, and dry mouth 7

Critical Safety Warnings

Serious Adverse Effects

• CNS depression and sedation occur frequently, which may be advantageous when sedation is desired but problematic otherwise 2
• Hypotension, particularly with rapid IV administration, is common 2
• Respiratory depression is a potential adverse effect, especially when combined with opioids or other CNS depressants 2, 7
• Extrapyramidal symptoms including dystonia can occur, though less commonly than with metoclopramide 7
• Neuroleptic malignant syndrome is a rare but serious adverse effect 1

Administration Precautions

• Peripheral IV administration can cause severe tissue injury including gangrene; if IV route is necessary, use deep IM injection or ensure proper IV placement with slow infusion 1, 7
• Promethazine is inappropriate for chronic use due to cumulative risks 7

Sequential Use with Ondansetron

• Sequential use of promethazine after ondansetron failure is pharmacologically sound, as they target different receptor systems (5-HT3 vs dopamine) 7
• The American Gastroenterological Association recommends using promethazine 12.5-25 mg when ondansetron or other 5-HT3 antagonists fail to control symptoms 2
• Monitor for excessive sedation when adding promethazine after ondansetron, especially in elderly patients or those on other CNS depressants 7