BENADRYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BENADRYL (BENADRYL).
Antihistamine; inverse agonist at histamine H1 receptors, blocking histamine-induced vasodilation, increased capillary permeability, and bronchoconstriction; also anticholinergic and sedative.
| Metabolism | Hepatic via CYP2D6 and CYP450; extensive first-pass metabolism; major metabolite is diphenhydramine N-oxide. |
| Excretion | Renal (90% as metabolites, <5% unchanged); minimal biliary/fecal. |
| Half-life | Terminal elimination half-life 4-8 hours; prolonged in hepatic impairment (up to 20 hours). |
| Protein binding | 98-99% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Vd ~3-4 L/kg; indicates extensive tissue distribution, including CNS penetration. |
| Bioavailability | Oral: 40-60% (first-pass metabolism); IM: nearly 100%; IV: 100%. |
| Onset of Action | Oral: 15-30 min; IM: 10-15 min; IV: 1-3 min; Topical: 30-60 min. |
| Duration of Action | Oral: 4-6 hours; IM/IV: 4-6 hours; Topical: 3-5 hours. Sedative effects may persist longer. |
| Brand Substitutes | Intadryl Syrup, Odaril Syrup, Tussberry-N Syrup, New Brethese Syrup, Suntuss CF Syrup |
25-50 mg orally every 4-6 hours as needed; maximum 300 mg per day. Alternatively, 10-50 mg intramuscularly or intravenously once, maximum 100 mg per dose (IV route preferred).
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment required for mild to moderate renal impairment; use with caution in severe renal impairment (CrCl <30 mL/min) due to risk of accumulation and anticholinergic effects. |
| Liver impairment | No specific dose adjustment for Child-Pugh class A or B; use with caution in severe hepatic impairment (Child-Pugh class C) due to reduced clearance; consider dose reduction or extended dosing interval. |
| Pediatric use | Children >2 years: 5 mg/kg/day divided every 6 hours, maximum 150 mg/day; alternatively, based on age: 6-12 years: 12.5-25 mg every 4-6 hours, maximum 150 mg/day; 2-6 years: 6.25-12.5 mg every 4-6 hours, maximum 75 mg/day; not recommended for children <2 years. |
| Geriatric use | Start with 25 mg orally once daily at bedtime; increase as needed and tolerated; avoid due to increased risk of confusion, sedation, and anticholinergic effects; consider alternative agents. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BENADRYL (BENADRYL).
| Breastfeeding | Diphenhydramine is excreted into breast milk in small amounts (M/P ratio approximately 0.5-1.0). Infant exposure is low via breastfeeding; however, it may cause drowsiness or irritability in some infants. Use with caution, especially in neonates or premature infants due to potential sedative effects. American Academy of Pediatrics considers compatible with breastfeeding. |
| Teratogenic Risk | First trimester: Limited human data suggests no significant increase in major malformations; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: No evidence of fetal harm; however, high doses near term may cause uterine irritability or neonatal withdrawal if used chronically. Risk category B (FDA). |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to diphenhydramine, neonates (especially premature), breastfeeding, concurrent use of MAOIs, narrow-angle glaucoma, symptomatic prostatic hypertrophy, bladder neck obstruction, acute asthma attack.
| Precautions | CNS depression (avoid with other CNS depressants), anticholinergic effects (elderly, glaucoma, urinary retention), paradoxical excitation in children, respiratory depression in infants, QT prolongation with overdose, avoid in breastfeeding (may cause infant irritability), use caution in hepatic/renal impairment. |
| Food/Dietary | Alcohol should be avoided as it potentiates CNS depression. No specific food restrictions. Grapefruit juice may increase absorption but not clinically significant. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate if given intravenously; assess for excessive sedation, urinary retention, or anticholinergic effects. In late pregnancy, monitor uterine contractions and fetal heart rate if used near term. No specific fetal monitoring required for short-term oral use. |
| Fertility Effects | No adverse effects on fertility reported in animal studies or human data. Anticholinergic effects may theoretically affect implantation via altered cervical mucus, but no clinical evidence supports significant impact. |
| Clinical Pearls | BENADRYL (diphenhydramine) is a first-generation antihistamine with strong anticholinergic properties. It is used for allergic reactions, motion sickness, and as a sleep aid. Avoid in elderly due to increased risk of confusion, falls, and anticholinergic toxicity. Use with caution in benign prostatic hyperplasia, glaucoma, and hepatic impairment. Rapid IV administration can cause hypotension and arrhythmias. It is a potent sedative; warn patients not to drive or operate machinery. Tolerance to sedation develops with repeated use. For acute dystonic reactions, BENADRYL is the treatment of choice (25-50 mg IV/IM). |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · This medication may cause drowsiness; avoid driving or operating heavy machinery until you know how it affects you. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they increase sedation. · Do not use for more than 2 weeks for sleep without consulting a doctor. · If you have difficulty urinating, blurred vision, or rapid heartbeat, contact your healthcare provider. · For motion sickness, take 30-60 minutes before travel. · Store at room temperature away from heat and light. |