Diphenhydramine

First-generation antihistamine (ethanolamine), Anticholinergic, Sleep aid, Antiemetic

Diphenhydramine (hydrochloride; citrate)

Benadryl (oral, injectable, topical), Banophen, Sominex (sleep aid), ZzzQuil, Aler-Dryl

Experience

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Titration strategies

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Effects

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Summary

Classes

First-generation antihistamine (ethanolamine), Anticholinergic, Sleep aid, Antiemetic

Pharmacy

Starting dose

Allergy: 25-50 mg PO every 4-6 hours. Insomnia: 25-50 mg PO at bedtime. IV (acute dystonia, severe allergic reaction): 25-50 mg slow IV push

Preparations

Tablets 25, 50 mg; capsules; liquid; chewable; topical cream/gel; injection 50 mg/mL

US FDA Max

300 mg/day (oral)

Pharmacology

Routes

Oral, IV, IM, topical

Onset

15-30 minutes (oral); 1-2 minutes (IV)

Duration

4-6 hours

Half-life

4-8 hours (longer in elderly, 9-13 hours)

Bioavailability

~40-60% (oral, with significant first-pass)

Pregnancy

Older agent with substantial use experience; broadly considered safe in pregnancy

Legal status

OTC for most oral and topical formulations; Rx-only for injectable

Purported mechanism

First-generation H1 histamine receptor antagonist with substantial central nervous system penetration and strong muscarinic acetylcholine receptor antagonism. The H1 blockade produces antihistamine and antiemetic effects; the muscarinic blockade produces sedation, anticholinergic burden (dry mouth, blurred vision, urinary retention, cognitive impairment), and at supratherapeutic doses, anticholinergic delirium with classic toxidrome ("blind as a bat, mad as a hatter").▲0▼ Major Beers-list concern in elderly patients for cognitive and fall risks. CYP2D6 substrate. At massive overdose, also produces sodium channel blockade with cardiac toxicity.

Dry mouth👤 100% -67.0 (n=1)⚕️ no reports yetRate×