diphenhydramine BENADRYL
Class: AntihistamineFDA Indications: Allergic Reaction, Motion Sickness, Parkinsonism, Insomnia
Off-Label Use: Antiemetic, Acute Dystonia
Prescribing
Forms: 25, 50mg capsule; 25, 50mg tablet; 12.5mg/5mL (most children's formulations); 50mg/30mL (ZzzQuil) po soln; 50 mg/mL injectableDose Range: 25-300 mg/day
Starting: 25-50 mg PO q6-8hr (allergies); 50 mg PO 30 minutes before bedtime (insomnia); 25 mg PO q8hr initially, then 50 mg PO q6hr; not to exceed 300 mg/day (Parkinsonism)
Precautions
Contraindications: Use with caution in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, or bladder-neck obstruction.Conditional Risk of TdP, Drugs to Avoid in Congenital Long QT
Side Effects: sedation/somnolence, dizziness, confusion, anticholinergic side effects, ataxia
Pharmacodynamics
1° MOA: H1 receptor antagonism within the TMN of the posterior hypothalamus, where the normal release of histamine during the day causes arousal, and its ↓'d release at night ↓'s arousal responses.2° MOA: Centrally-acting antimuscarinic agent; reinstates balance of dopaminergic to cholinergic activity in the nigrostriatal pathway.
Target: H1, M1
Pharmacokinetics
t½: 9 (6-12)° TMAX: 2°Substrate of: 2D6; 3A4
Inhibits: ∅ ; Induces: ∅
Active Metabolites: Nordiphenhydramine
DDIs
- - co-prescribed 2D6 inhibitors can ↑ serum levels
- - caution when prescribing with other CNS depressants
Misc
- - also exhibit antimuscarinic activity, leading to corresponding side effects such as dry mouth, urinary retention, vand blurred vision
- - long t½ → daytime drowsiness and residual next-day sedation; these next-day effects can lead to impaired cognition and performance
Special Populations
Category B—Both animal & published human experience suggest that diphenhydramine is safe for use in human pregnancy. At least one review has concluded that diphenhydramine is the drug of choice if parenteral antihistamines are indicated in pregnancy.
Diphenhydramine is excreted into human breast milk, but levels have not been reported. Although the levels are not thought to be sufficiently high to affect the infant after therapeutic doses, the manufacturer considers the drug contraindicated in nursing mothers. The reason given for this is the increased sensitivity of newborn or premature infants to antihistamines.
Avoid as its more likely to cause anticholinergic side effects in elderly patients AND more likely to accumulate d/t its longer t½ in the elderly (13.5°)
2019 BEE℞S Recommendation: Avoid. Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity
No dosage adjustment necessary.
Dosage reduction may be warranted for patients with hepatic impairment; diphenhydramine is extensively metabolized in the liver.