DIPHENHYDRAMINE HYDROCHLORIDE PRESERVATIVE FREE
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; centrally acting anticholinergic agent that inhibits acetylcholine muscarinic receptors.
| Metabolism | Primarily hepatic via CYP2D6, minor via CYP1A2, CYP2C9, and CYP2C19; forms diphenylmethoxyacetic acid and nor-diphenhydramine. |
| Excretion | Primarily renal as inactive metabolites; ~60% of a dose appears in urine as metabolites, with <5% unchanged. Minor biliary/fecal elimination (<10%). |
| Half-life | Terminal elimination half-life: 4-10 hours (mean ~8 hours); prolonged in hepatic impairment or elderly (up to 20 hours). |
| Protein binding | ~78-80% bound to albumin. |
| Volume of Distribution | 3-10 L/kg; large due to extensive tissue distribution, crossing blood-brain barrier. |
| Bioavailability | Oral: 50-70% due to first-pass metabolism; IM: near 100%. |
| Onset of Action | IM: 15-30 minutes; IV: immediate (2-5 minutes); oral: 15-45 minutes. |
| Duration of Action | IM/IV: 4-6 hours; oral: 4-6 hours; suppressed wheal-and-flare response up to 12 hours. |
25 to 50 mg intravenously or intramuscularly every 4 to 6 hours as needed; maximum 400 mg per day.
| Dosage form | INJECTABLE |
| Renal impairment | For GFR 10-50 mL/min: administer 25 mg every 6 hours; for GFR <10 mL/min: administer 25 mg every 12 hours. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B or C: reduce dose by 50% and administer every 12 hours. |
| Pediatric use | 1 to 2 mg/kg intravenously or intramuscularly every 4 to 6 hours as needed; maximum 300 mg per day. |
| Geriatric use | Initiate at 25 mg intravenously or intramuscularly every 6 hours; monitor for anticholinergic effects and cognitive impairment; avoid routine use due to Beers Criteria recommendation. |
| 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 | Excreted into breast milk in small amounts; M/P ratio approximately 0.5–1.0. Theoretical risk of sedation or irritability in infants; use with caution, especially in neonates or preterm infants. American Academy of Pediatrics considers generally compatible with breastfeeding. |
| Teratogenic Risk | FDA Pregnancy Category B. First trimester: No evidence of increased risk of major malformations in human studies; however, animal studies are inadequate. Second and third trimesters: Use not associated with teratogenicity; risk of uterine contractions with high doses near term. Avoid in late pregnancy due to potential for oxytocic effects. |
■ FDA Black Box Warning
Not recommended for use in children younger than 2 years due to risk of respiratory depression and death.
| Common Effects | insomnia |
| Serious Effects |
Hypersensitivity, narrow-angle glaucoma, prostatic hypertrophy, urinary retention, concurrent use with MAO inhibitors, neonates, premature infants, breastfeeding (high doses), and children under 2 years.
| Precautions | Avoid in patients with asthma, COPD, glaucoma, prostatic hyperplasia, urinary retention, and elderly patients due to increased risk of anticholinergic effects, sedation, and confusion. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and sedation level. Fetal heart rate monitoring recommended if used during labor due to potential uterine hyperstimulation. Assess for anticholinergic effects (dry mouth, urinary retention, blurred vision) in the mother. |
| Fertility Effects | Limited human data. Animal studies suggest no significant effects on fertility. Anticholinergic properties may theoretically affect cervical mucus or sperm motility, but not clinically relevant. |