How should promethazine (antihistamine) combined with dextromethorphan (cough suppressant) (Promethazine DM) be dosed in adults and children, and what are its contraindications and adverse effects?

Promethazine DM: Dosing, Contraindications, and Adverse Effects

Promethazine combined with dextromethorphan (Promethazine DM) should be used cautiously and only for short-term symptomatic relief of cough in adults and children over 2 years of age, with oral administration strongly preferred over parenteral routes due to significant safety concerns. 1, 2

Adult Dosing

• Standard dose: Promethazine 12.5-25 mg combined with dextromethorphan every 4-6 hours as needed for cough suppression 1
• Lower doses (6.25-12.5 mg promethazine) are equally effective for symptom control and cause significantly less sedation 1, 3
• Maximum dosing interval is every 4 hours; avoid more frequent administration 1
• Duration of action is 4-6 hours after a single dose, though effects may persist up to 12 hours 1
• Onset of action occurs within 20 minutes when given orally 1

Pediatric Considerations

• Contraindicated in children under 2 years of age due to risks of significant sedation, agitation, hallucinations, seizures, and possible sudden infant death syndrome 4
• For children over 2 years: dose should be weight-based and significantly lower than adult dosing 4
• Evidence shows dextromethorphan and promethazine are not superior to placebo for nocturnal cough in children with upper respiratory infections 5
• Oral administration is equivalent to parenteral if GI absorption is intact 1

Critical Contraindications

Absolute Contraindications

• Children under 2 years of age 4
• Significant hepatic impairment (promethazine is hepatotoxic and may precipitate coma) 6
• Concurrent use with other CNS depressants or opioids without careful monitoring 1

Relative Contraindications and High-Risk Populations

• Elderly patients: Higher risk of cognitive impairment, anticholinergic side effects, and falls 1
• Prostatic hypertrophy, elevated intraocular pressure, or existing cognitive impairment: Increased risk of adverse anticholinergic effects 1
• Severe renal impairment (creatinine clearance <10 mL/min) 6
• Pregnancy, especially first trimester (though not proven teratogenic, avoidance is recommended) 6

Major Adverse Effects

Serious Tissue Damage (Parenteral Administration)

• IV administration carries risk of thrombophlebitis, tissue necrosis, and gangrene 1, 2
• If IV route is absolutely necessary, use slow infusion (≤25 mg/min) and ensure proper IV placement 1
• Intramuscular administration is strongly preferred over IV: deltoid muscle in adults, vastus lateralis in children 7

Central Nervous System Effects

• Significant sedation, particularly problematic with repeated dosing or when combined with opioids 1, 3
• Respiratory depression risk increases with cumulative dosing 1
• Agitation, hallucinations, and seizures reported, especially in children 4
• Cognitive impairment and anticholinergic effects (confusion, urinary retention, dry mouth) 1, 3

Extrapyramidal Reactions

• Dystonia, akathisia, and neuroleptic malignant syndrome can occur 1
• Have diphenhydramine 25-50 mg readily available for prompt treatment if extrapyramidal symptoms arise 1
• These risks make promethazine inappropriate for chronic use 1

Cardiovascular Effects

• Hypotension with rapid IV administration 1
• Palpitations and elevated blood pressure (from combination products containing decongestants) 6

Abuse Potential

• Promethazine-dextromethorphan combinations have significant misuse/abuse potential, especially in adolescents 8, 9
• Associated with drug-related fatalities, particularly when combined with opioids 8
• Healthcare professionals should be vigilant, as promethazine products can be purchased over-the-counter in some countries 8

Administration Guidelines

Route Selection

• Oral administration is strongly preferred due to safety profile 1, 2
• Oral bioavailability is 25%, but current dosing accounts for this 1
• Avoid IV route when possible; if parenteral administration is necessary, use deep IM injection 1, 7

Monitoring Requirements

• Monitor for excessive sedation, especially in elderly patients or those on other CNS depressants 1, 3
• Watch for extrapyramidal symptoms (dystonia, akathisia) 1
• Assess for anticholinergic effects including confusion, urinary retention, and dry mouth 3

Clinical Efficacy Considerations

• Nocturnal cough in upper respiratory infections is self-resolving; dextromethorphan and promethazine are not superior to placebo 5
• Adverse effects are more frequent with active medications compared to placebo, though differences may not reach statistical significance 5
• Consider whether symptomatic treatment is truly necessary given the self-limited nature of most upper respiratory infections 5

Key Clinical Pitfalls to Avoid

• Never use in children under 2 years 4
• Avoid chronic or repeated use due to extrapyramidal and respiratory depression risks 1
• Do not administer IV unless absolutely necessary, and never via peripheral IV without extreme caution 1, 2
• Do not combine with opioids or other CNS depressants without careful risk-benefit assessment 1, 8
• Be aware of abuse potential, particularly in adolescents and young adults 8, 9