DARIFENACIN HYDROBROMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DARIFENACIN HYDROBROMIDE (DARIFENACIN HYDROBROMIDE).
Darifenacin is a competitive muscarinic receptor antagonist, with high selectivity for the M3 receptor subtype, which mediates bladder contraction. By blocking M3 receptors in the detrusor muscle, it reduces bladder contractility and increases bladder capacity.
| Metabolism | Primarily metabolized by CYP2D6 and CYP3A4 to inactive metabolites. Minor contributions from CYP2C9, CYP2C19, and CYP2E1. |
| Excretion | Approximately 60% renal (as metabolites, <3% unchanged) and 40% fecal (primarily as metabolites). |
| Half-life | Terminal elimination half-life is approximately 13-19 hours; clinically, steady-state is reached within 3-5 days. |
| Protein binding | Approximately 98% bound, primarily to alpha-1-acid glycoprotein. |
| Volume of Distribution | About 1.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 15-20% due to first-pass metabolism. |
| Onset of Action | Oral: within 1-2 hours after administration. |
| Duration of Action | Approximately 24 hours, supporting once-daily dosing. |
7.5 mg to 15 mg orally once daily, with or without food.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-89 mL/min: No adjustment necessary. GFR <30 mL/min: Not recommended (no data). |
| Liver impairment | Child-Pugh Class A: No adjustment necessary. Child-Pugh Class B: Maximum dose 7.5 mg once daily. Child-Pugh Class C: Not recommended. |
| Pediatric use | Safety and efficacy not established; no FDA-approved pediatric dosing. |
| Geriatric use | Start at 7.5 mg once daily; may increase to 15 mg if tolerated. Monitor for anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARIFENACIN HYDROBROMIDE (DARIFENACIN HYDROBROMIDE).
| Breastfeeding | It is unknown if darifenacin is excreted in human milk. In animal studies, darifenacin was detected in rat milk. M/P ratio not determined. Due to potential for anticholinergic effects in infant, caution advised; consider alternative agents during breastfeeding. |
| Teratogenic Risk | Darifenacin is FDA Pregnancy Category C. No adequate well-controlled studies in pregnant women. In animal studies, no teratogenic effects observed at doses up to 50 mg/kg/day (rat) and 30 mg/kg/day (rabbit), but fetotoxicity (reduced fetal weight, delayed ossification) occurred at maternally toxic doses. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. First trimester: unknown risk; second/third trimester: limited data; avoid unless necessary. |
■ FDA Black Box Warning
None
| Serious Effects |
["Urinary retention","Gastric retention","Uncontrolled narrow-angle glaucoma","Hypersensitivity to darifenacin or any component of the formulation"]
| Precautions | ["Risk of urinary retention (especially in patients with bladder outflow obstruction)","Central nervous system effects (e.g., somnolence, dizziness) due to potential CNS penetration","Exacerbation of angle-closure glaucoma in predisposed patients","Decreased gastrointestinal motility (caution in patients with severe constipation or gastric retention)","Hepatic impairment reduces clearance; dose adjustment recommended in moderate impairment"] |
| Food/Dietary | No clinically significant food interactions. Avoid grapefruit juice due to potential CYP3A4 inhibition, though effect is weak. |
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| Fetal Monitoring | Monitor for anticholinergic side effects (dry mouth, constipation, blurred vision, urinary retention). No specific fetal monitoring required; fetal growth and well-being as per routine obstetric care. Assess for maternal dehydration or constipation. |
| Fertility Effects | No human data on fertility effects. In animal studies, darifenacin did not impair fertility in rats at doses up to 50 mg/kg/day. Anticholinergic effects may theoretically affect libido or erectile function, but no clinical evidence. |
| Clinical Pearls | Darifenacin is a selective M3 muscarinic receptor antagonist used for overactive bladder. Start at 7.5 mg/day; increase to 15 mg/day if needed. CYP3A4 substrate; reduce dose to 7.5 mg/day when used with potent CYP3A4 inhibitors (e.g., ketoconazole). Contraindicated in urinary retention, gastric retention, uncontrolled narrow-angle glaucoma. |
| Patient Advice | Take with or without food; swallow tablet whole with liquid. · Avoid driving or operating machinery until you know how the medication affects you; may cause blurred vision or dizziness. · Do not take with strong CYP3A4 inhibitors (certain antifungals, antibiotics) without consulting your doctor. · Report difficulty urinating, constipation, or severe abdominal pain immediately. · Store at room temperature, away from moisture and heat. |