BENYLIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BENYLIN (BENYLIN).
BENYLIN (diphenhydramine) is a first-generation antihistamine that competitively antagonizes histamine at H1 receptors, thereby alleviating allergic symptoms. It also crosses the blood-brain barrier and acts as a central nervous system depressant via inhibition of histamine and acetylcholine, producing sedative, antiemetic, and antitussive effects.
| Metabolism | Primarily metabolized in the liver via N-demethylation and oxidation by cytochrome P450 enzymes, including CYP2D6. Some metabolites are pharmacologically active. Diphenhydramine undergoes first-pass metabolism and is excreted mainly in urine as metabolites, with a small amount unchanged. |
| Excretion | Renal: ~80% as unchanged drug and glucuronide conjugates; fecal/biliary: ~20%. |
| Half-life | Terminal elimination half-life: 4-6 hours in adults; extended to 10-12 hours in hepatic impairment, increasing risk of accumulation. |
| Protein binding | ~50-60% bound to albumin. |
| Volume of Distribution | 5-7 L/kg; large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: ~40% due to first-pass metabolism; rectal: ~50-60%. |
| Onset of Action | Oral: 15-30 minutes; IV: 1-2 minutes. |
| Duration of Action | 4-6 hours for antitussive effect; overdose or hepatic impairment may prolong. |
Oral: 10-20 mL (25-50 mg diphenhydramine) every 4-6 hours; maximum 100 mg per day.
| Dosage form | SYRUP |
| Renal impairment | GFR 10-50 mL/min: administer every 6-8 hours; GFR <10 mL/min: administer every 8-12 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: administer every 8 hours; Child-Pugh Class C: administer every 12 hours. |
| Pediatric use | Oral: 1 mg/kg per dose every 4-6 hours; maximum 5 mg/kg per day; for >12 years, use adult dose. |
| Geriatric use | Initiate at 50% of adult dose; maximum 50 mg per day; monitor for sedation and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BENYLIN (BENYLIN).
| Breastfeeding | Diphenhydramine is excreted into breast milk in small amounts; M/P ratio unknown. Infants may be at risk of sedation or irritability. Caution is advised, especially in preterm infants or those with apnea risk. Alternatives preferred in breastfeeding. |
| Teratogenic Risk | First trimester: No increased risk of major malformations reported based on limited human data; antihistamines generally considered low risk. Second and third trimesters: Use near term may cause respiratory depression, irritability, or paradoxical excitement in the neonate; avoid in third trimester due to risk of kernicterus (theoretical, rare). |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to diphenhydramine or any component of the formulation. Acute asthma attack. Use in premature and newborn infants (due to risk of paradoxical excitation and apnea). Breastfeeding (may cause drowsiness or irritability in infants). Concomitant use with monoamine oxidase inhibitors (MAOIs).
| Precautions | Sedation and drowsiness may impair ability to drive or operate machinery. Anticholinergic effects (dry mouth, urinary retention, constipation, blurred vision) are common. Use caution in patients with asthma, COPD, glaucoma, prostatic hyperplasia, urinary obstruction, or hyperthyroidism. Elderly patients are more susceptible to confusion, hypotension, and anticholinergic side effects. Not recommended for use in children <2 years due to risk of respiratory depression. Concomitant use with other CNS depressants (alcohol, opioids, sedatives) potentiates sedation. Avoid prolonged use for insomnia. |
| Food/Dietary | Grapefruit juice may increase diphenhydramine absorption; alcohol and sedative foods (e.g., chamomile, valerian) potentiate CNS depression. |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate (anticholinergic effects). Fetal monitoring for signs of distress if used in third trimester. Neonatal observation for sedation or irritability after delivery if used near term. |
| Fertility Effects | Limited data; no direct evidence of adverse effects on fertility. Diphenhydramine may affect ovulation via anticholinergic mechanisms but clinical significance unknown. |
| Clinical Pearls | Benylin (diphenhydramine) is a first-generation antihistamine with strong anticholinergic properties; may exacerbate narrow-angle glaucoma, urinary retention, and cognitive impairment in elderly. Avoid in children under 6 years due to paradoxical excitation risk. |
| Patient Advice | Causes marked drowsiness; do not drive or operate machinery. · Avoid alcohol and other CNS depressants. · Use caution if you have glaucoma, enlarged prostate, or breathing problems. · Do not exceed recommended dose; may cause dry mouth, blurred vision, and constipation. · For cough: use only for dry, non-productive cough. |