DIPHEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIPHEN (DIPHEN).
Diphenhydramine is a first-generation antihistamine that competitively antagonizes histamine at H1 receptors. It also exhibits anticholinergic, sedative, antiemetic, and local anesthetic effects.
| Metabolism | Primarily metabolized by CYP2D6 to diphenylmethoxyacetic acid and other metabolites. Undergoes first-pass metabolism. Metabolites are excreted in urine. |
| Excretion | Primarily hepatic metabolism; renal excretion of inactive metabolites accounts for ~70% of eliminated drug; biliary/fecal excretion accounts for ~30%. |
| Half-life | Terminal elimination half-life is 22–72 hours (mean 30–40 hours); increases with hepatic disease or enzyme inhibitors. |
| Protein binding | 85–90%, primarily to albumin. |
| Volume of Distribution | 0.5–1.0 L/kg; distributes into CSF and brain. |
| Bioavailability | Oral: 70–80% (tablets/capsules). |
| Onset of Action | Oral: 30–60 minutes; intravenous: <5 minutes. |
| Duration of Action | Oral: 6–8 hours; intravenous: 4–6 hours. Titrated based on seizure control. |
50 mg IV/IM every 4 hours as needed for nausea/vomiting; 25-50 mg PO every 4-6 hours as needed for nausea/vomiting or motion sickness; 25 mg PO 3-4 times daily for vertigo; 15.6-25 mg IM/IV for antiemetic in surgery; maximum 300 mg/day.
| Dosage form | SYRUP |
| Renal impairment | CrCl <10 mL/min: dose reduction to 50% of usual dose recommended; monitor for CNS effects. |
| Liver impairment | Child-Pugh Class C: avoid use; Class A or B: dose reduction to 50% of usual dose; monitor for sedation. |
| Pediatric use | Children >2 years: 5 mg/kg/day PO/IM/IV in 3-4 divided doses, maximum 15 mg/kg/day; <2 years: not recommended due to risk of respiratory depression. |
| Geriatric use | Elderly: initiate at 25 mg PO once daily or 12.5 mg IM/IV; increase cautiously; avoid prolonged use due to anticholinergic effects and sedation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIPHEN (DIPHEN).
| Breastfeeding | Safety not established. M/P ratio unknown. May cause sedation or hypotonia in breastfed infants. Use only if potential benefit outweighs risk. |
| Teratogenic Risk | Fetal risk cannot be ruled out. First trimester: Limited human data; animal studies show no teratogenicity. Second/Third trimester: Potential for fetal respiratory depression and hypotonia if used near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to diphenhydramine or other antihistamines","Neonates and premature infants","Breastfeeding (use with caution)","Acute asthma attack","Use with monoamine oxidase inhibitors (MAOIs) (caution)"]
| Precautions | ["Anticholinergic effects (e.g., confusion, urinary retention, blurred vision) especially in elderly","Sedation and impairment of cognitive/motor function","Risk of falls in elderly","Extrapyramidal symptoms with high doses","Respiratory depression in young children or with overdose","Interference with skin tests for allergies"] |
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| Monitor maternal vital signs, respiratory rate, and sedation level. In term pregnancy, assess neonatal respiratory status at delivery. |
| Fertility Effects | No known effect on fertility; limited evidence suggests potential for menstrual irregularities at high doses. |