DIBENIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIBENIL (DIBENIL).
Dibenzazepine-derived tricyclic antidepressant that primarily inhibits norepinephrine reuptake, with lesser effects on serotonin reuptake, and has anticholinergic properties.
| Metabolism | Hepatic via CYP2D6, CYP1A2, and CYP3A4; active metabolite desipramine via N-demethylation. |
| Excretion | Primarily renal excretion of unchanged drug (60-70%) and its active metabolite (20-30%); minor biliary/fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is approximately 6-8 hours; prolonged to 12-18 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 95%, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.3 L/kg, indicating limited extravascular distribution; clinical note: low Vd suggests predominantly central compartment distribution. |
| Bioavailability | Oral: 80-90% due to extensive first-pass metabolism; Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | 8-12 hours after standard oral dose; may be extended in renal impairment or with high doses. |
250 mg orally twice daily or 500 mg once daily, with meals.
| Dosage form | ELIXIR |
| Renal impairment | eGFR 30-59 mL/min: 250 mg once daily. eGFR <30 mL/min or dialysis: 125 mg once daily. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 250 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Not established for children under 12 years; for adolescents 12-18 years, 250 mg twice daily. |
| Geriatric use | Start at 125 mg twice daily; titrate slowly; monitor renal function and QT interval. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIBENIL (DIBENIL).
| Breastfeeding | Diphenhydramine is excreted into breast milk in small amounts (M/P ratio ~0.5-1.0). It may cause irritability or drowsiness in infants. Caution advised; avoid high doses or prolonged use. American Academy of Pediatrics considers usually compatible with breastfeeding. |
| Teratogenic Risk | Dibenil (diphenhydramine) is an antihistamine. First trimester: No consistent evidence of major malformations; weak association with cleft palate in some studies. Second and third trimesters: No known teratogenicity; risk of neonatal withdrawal symptoms if used late in pregnancy. Uterine contractions may be inhibited at high doses. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
History of seizure disorder, recent myocardial infarction, concurrent MAOI use, narrow-angle glaucoma, urinary retention, hypersensitivity to tricyclics.
| Precautions | May cause sedation, orthostatic hypotension, QT prolongation, lowering of seizure threshold, activation of mania/hypomania, anticholinergic effects, serotonin syndrome, and withdrawal symptoms. |
Loading safety data…
| Fetal Monitoring | Monitor fetal heart rate and uterine activity if used intravenously or at high doses. Observe neonate for respiratory depression, sedation, or withdrawal if maternal use near term. No specific routine monitoring recommended for oral use. |
| Fertility Effects | Diphenhydramine has anticholinergic effects that may cause transient vaginal dryness or reduced cervical mucus, but no established effect on fertility. No evidence of impaired fertility or gametogenesis in humans. |