What are the guidelines for using promethazine (Phenergan) for nausea and sedation?

Promethazine Use for Nausea and Sedation

For nausea and vomiting, use promethazine 6.25-12.5 mg IV (infused slowly at ≤25 mg/min) or 12.5-25 mg orally/IM, with intramuscular administration preferred over intravenous due to serious tissue injury risks. 1, 2, 3

Dosing Guidelines

For Nausea and Vomiting

• Initial dose: 6.25-12.5 mg IV provides equal antiemetic efficacy to higher doses with significantly fewer adverse effects 4, 5
• Standard dose: 12.5-25 mg IV (infused slowly), oral, or IM; may repeat every 4-6 hours as needed 6, 2
• Maximum total dose: 25-50 mg when used as adjuvant therapy 1
• Lower doses (6.25 mg) are equally effective as ondansetron 4 mg for nausea relief at 1 and 3 hours (74% vs 59% at 1 hour) with less sedation 4

For Sedation

• Adults: 25-50 mg at bedtime or preoperatively 2
• Children: 12.5-25 mg at bedtime (0.5 mg per pound body weight for preoperative use) 2

For Pruritus (Opioid-Induced)

• Dose: 12.5-25 mg orally every 6 hours 6

Route-Specific Administration

Intravenous (Use with Extreme Caution)

• Critical safety requirement: Infuse slowly at ≤25 mg/min to minimize hypotension risk 6, 1
• FDA warning: Injectable promethazine carries risk of serious limb-threatening tissue injury from extravasation or inadvertent intra-arterial injection 3
• Onset: Within 5 minutes 6, 1
• Preferred alternative: Intramuscular route is safer and recommended by FDA as of December 2023 3

Intramuscular (Preferred Parenteral Route)

• Adults and older children: Deltoid muscle 7
• Infants and young children: Vastus lateralis (anterolateral thigh) 7
• Onset: Within 20 minutes 1

Oral

• Onset: Within 20 minutes 1
• Duration: 4-6 hours (effects may persist up to 12 hours) 6, 1

Critical Safety Considerations

Absolute Contraindications

• Children under 2 years of age: Black box warning due to respiratory depression risk 2, 8

Serious Adverse Effects Requiring Caution

• Respiratory depression: Risk increases with cumulative dosing and when combined with opioids 1
• Extrapyramidal effects: Including neuroleptic malignant syndrome, dystonia, and oculogyric crises—makes promethazine inappropriate for chronic use 6, 1, 9
• Tissue damage: Thrombophlebitis, tissue necrosis, and gangrene with IV administration 1, 3
• Hypotension: Particularly with rapid IV infusion 6, 1
• Significant sedation: Especially problematic with repeated dosing or opioid co-administration 1, 9

Common Adverse Effects

• Sedation, confusion, uncooperative behavior during procedures 6
• In elderly patients, 6.25 mg causes significantly fewer adverse reactions than 12.5 mg 5

Clinical Context and Alternatives

When to Consider Promethazine

• As adjuvant to opioids and benzodiazepines for procedural sedation (may allow dose reduction of primary sedatives) 6, 1
• When ondansetron and other antiemetics are unavailable or ineffective 3
• For opioid-induced pruritus when antihistamines are indicated 6

When to Avoid Promethazine

• Ondansetron is increasingly preferred due to superior safety profile, lack of CNS/autonomic side effects, and absence of tissue injury risk 9
• Patient safety organizations have called for removal of injectable promethazine from hospital formularies 3
• Promethazine should not be used chronically due to extrapyramidal effects 1

Key Pitfalls to Avoid

1. Never use in children under 2 years: Respiratory depression risk is unacceptable 2, 8
2. Never infuse IV rapidly: Always infuse at ≤25 mg/min to prevent hypotension 6, 1
3. Avoid IV route when IM is feasible: Tissue injury risk makes IM the preferred parenteral route 3
4. Reduce opioid doses: When using promethazine as adjuvant, standard sedation agent doses must be reduced 6, 1
5. Start with lowest effective dose: 6.25 mg IV is as effective as 25 mg with fewer adverse effects 4, 5