Comparative Pharmacology
Head-to-head clinical analysis: DIPHEN versus PROMETHAZINE W CODEINE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DIPHEN versus PROMETHAZINE W CODEINE.
DIPHEN vs PROMETHAZINE W/ CODEINE
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Diphenhydramine is a first-generation antihistamine that competitively antagonizes histamine at H1 receptors. It also exhibits anticholinergic, sedative, antiemetic, and local anesthetic effects.
Codeine is a prodrug converted to morphine, a mu-opioid receptor agonist, which inhibits nociceptive transmission; promethazine is a phenothiazine derivative with H1-receptor antagonism, anticholinergic, and antiemetic effects.
50 mg IV/IM every 4 hours as needed for nausea/vomiting; 25-50 mg PO every 4-6 hours as needed for nausea/vomiting or motion sickness; 25 mg PO 3-4 times daily for vertigo; 15.6-25 mg IM/IV for antiemetic in surgery; maximum 300 mg/day.
10 mL (1 mg codeine, 6.25 mg promethazine per 5 mL) orally every 4-6 hours as needed for cough. Maximum: 60 mL per day. Do not exceed 5 days.
None Documented
None Documented
Clinical Note
moderateDiphenoxylate + Torasemide
"The risk or severity of adverse effects can be increased when Diphenoxylate is combined with Torasemide."
Clinical Note
moderateDiphenoxylate + Etacrynic acid
"The risk or severity of adverse effects can be increased when Diphenoxylate is combined with Etacrynic acid."
Clinical Note
moderateDiphenoxylate + Furosemide
"The risk or severity of adverse effects can be increased when Diphenoxylate is combined with Furosemide."
Clinical Note
moderateTerminal elimination half-life is 22–72 hours (mean 30–40 hours); increases with hepatic disease or enzyme inhibitors.
Promethazine: 10-19 hours (terminal). Codeine: 2.5-3.5 hours (terminal); prolonged in renal impairment.
Primarily hepatic metabolism; renal excretion of inactive metabolites accounts for ~70% of eliminated drug; biliary/fecal excretion accounts for ~30%.
Promethazine: renal (70% as metabolites, <1% unchanged), fecal (20-30%). Codeine: renal (90%, of which 5-10% unchanged, rest as metabolites), fecal (minor).
Category C
Category A/B
Antihistamine
Antihistamine / Antiemetic
Diphenoxylate + Bumetanide
"The risk or severity of adverse effects can be increased when Diphenoxylate is combined with Bumetanide."