Comparative Pharmacology
Head-to-head clinical analysis: DIPHENHYDRAMINE versus PROMETHAZINE W DEXTROMETHORPHAN.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DIPHENHYDRAMINE versus PROMETHAZINE W DEXTROMETHORPHAN.
Diphenhydramine vs PROMETHAZINE W/ DEXTROMETHORPHAN
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Inverse agonist at histamine H1 receptors, blocking histamine-mediated effects in blood vessels, respiratory smooth muscle, and GI tract; also anticholinergic by blocking muscarinic receptors and sedative via central H1 receptor antagonism.
Promethazine is a phenothiazine derivative that acts as a histamine H1 receptor antagonist and antiemetic; dextromethorphan is a non-opioid antitussive that acts as an NMDA receptor antagonist and sigma-1 receptor agonist.
25-50 mg orally or intramuscularly every 4-6 hours; maximum 300 mg/day. Intravenous administration: 10-50 mg slow IV push (max 25 mg/min).
5 mL (containing promethazine 6.25 mg and dextromethorphan 15 mg) orally every 4-6 hours as needed, not to exceed 30 mL (promethazine 37.5 mg, dextromethorphan 90 mg) per 24 hours.
None Documented
None Documented
Clinical Note
moderateDiphenhydramine + Deferasirox
"The serum concentration of Deferasirox can be increased when it is combined with Diphenhydramine."
Clinical Note
moderateDiphenhydramine + Fluticasone propionate
"The risk or severity of adverse effects can be increased when Diphenhydramine is combined with Fluticasone propionate."
Clinical Note
moderateDiphenhydramine + Tenofovir disoproxil
"The metabolism of Tenofovir disoproxil can be decreased when combined with Diphenhydramine."
Clinical Note
moderateTerminal elimination half-life 4-8 hours in adults; prolonged in hepatic impairment (up to 20 hours) and elderly.
Promethazine: 9-16 h; dextromethorphan: 3-5 h (extensive metabolizers), 30-50 h (poor metabolizers). Clinical context: dosing interval typically 4-6 h for dextromethorphan; promethazine accumulates with repeated dosing.
Primarily renal (90-95% as metabolites, <5% unchanged). Minor biliary/fecal elimination (<5%).
Renal: promethazine ~6% unchanged, dextromethorphan ~0.5% unchanged; metabolites primarily renal. Biliary/fecal: minor routes for both.
Category C
Category A/B
Antihistamine
Antihistamine / Antiemetic
Diphenhydramine + Sulfisoxazole
"The metabolism of Sulfisoxazole can be decreased when combined with Diphenhydramine."