DIPHENHYDRAMINE HYDROCHLORIDE
Clinical safety rating: safe
CNS depressants may enhance sedative effects May cause marked drowsiness and impair mental and physical abilities.
Competitive antagonist of histamine H1 receptors, reducing allergic symptoms; also exerts anticholinergic, sedative, and antiemetic effects via central and peripheral receptor blockade.
| Metabolism | Primarily hepatic via CYP2D6; also via CYP1A2, CYP2C9, and CYP3A4. |
| Excretion | Renal elimination of metabolites accounts for ~60% of the dose; <5% excreted unchanged. Fecal excretion ~40% via bile. |
| Half-life | Terminal elimination half-life 4–10 hours (mean ~7 hours); prolonged in elderly, hepatic impairment, and with CYP2D6 poor metabolizers. |
| Protein binding | 78–85%, primarily to albumin. |
| Volume of Distribution | 3–7 L/kg; indicates extensive tissue distribution, including CNS. |
| Bioavailability | Oral: 40–60% (first-pass metabolism); IM: ~100%; IV: 100%. |
| Onset of Action | Oral: 15–30 minutes; IM: 10–20 minutes; IV: 5–10 minutes. Topical: 20–30 minutes. |
| Duration of Action | 4–6 hours for antihistaminic effect; up to 12 hours for sedation. Duration shorter with rapid tolerance to sedation. |
25-50 mg orally or intramuscularly every 4-6 hours as needed; maximum 300 mg per day.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 10-50 mL/min: administer every 6-8 hours; eGFR <10 mL/min: administer every 8-12 hours. |
| Liver impairment | Child-Pugh Class A and B: no adjustment; Child-Pugh Class C: use with caution, reduce dose by 50%. |
| Pediatric use | 1 mg/kg orally or intramuscularly every 4-6 hours as needed; maximum 300 mg per day. |
| Geriatric use | Initiate at 25 mg orally or intramuscularly every 8 hours as needed; maximum 100 mg per day due to increased risk of confusion, sedation, and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants may enhance sedative effects May cause marked drowsiness and impair mental and physical abilities.
| FDA category | Animal |
| Breastfeeding | Present in breast milk in small amounts; M/P ratio approximately 0.5. Considered compatible with breastfeeding by AAP; monitor infant for drowsiness, irritability, or paradoxical excitation. Use lowest effective dose for shortest duration. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies show no fetal harm; no adequate human studies in first trimester. In third trimester, use near term may cause neonatal withdrawal symptoms (jitteriness, irritability) or respiratory depression. No established teratogenicity in first or second trimester. |
■ FDA Black Box Warning
None.
| Common Effects | insomnia |
| Serious Effects |
["Hypersensitivity to diphenhydramine or any component.","Avoid in neonates and premature infants.","Use in breastfeeding is not recommended due to potential adverse effects on infants.","Avoid in patients with narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, bladder neck obstruction, or prostatic hypertrophy."]
| Precautions | ["Avoid use in infants and neonates due to risk of paradoxical excitation and apnea.","Caution in elderly due to increased risk of confusion, falls, and anticholinergic effects.","May cause significant drowsiness; avoid driving or operating machinery.","Avoid concurrent use with alcohol or other CNS depressants.","Use with caution in patients with asthma, COPD, or urinary retention."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate; fetal heart rate if used intravenously in labor. Assess neonatal respiratory status and neurobehavior if used near term. |
| Fertility Effects | No known adverse effects on human fertility. In animal studies, no impairment of fertility at clinically relevant doses. |