DARIFENACIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DARIFENACIN (DARIFENACIN).
Competitive antagonist of muscarinic acetylcholine receptors (M1, M2, M3 subtypes), reducing detrusor muscle contractility.
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4; active metabolite (5-hydroxymethyl darifenacin) contributes to activity. |
| Excretion | Approximately 60% of the dose is excreted renally (as metabolites, primarily 3-hydroxydarifenacin) and 40% fecally; less than 3% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 13-19 hours in young adults, increasing to about 17 hours in elderly; supports once-daily dosing. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is about 1,000 L (≈14 L/kg for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 15-25% due to first-pass metabolism; taken once daily. |
| Onset of Action | Oral: Clinical effect on urinary symptoms (e.g., reduction in incontinence episodes) observed within 1-2 weeks; at receptor level, measurable effects within hours. |
| Duration of Action | Duration of action is approximately 24 hours with once-daily dosing; sustained symptomatic improvement over 24 hours. |
7.5 mg to 15 mg orally once daily
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No adjustment for GFR ≥30 mL/min; contraindicated if GFR <30 mL/min |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 7.5 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | Safety and efficacy not established in pediatric patients |
| Geriatric use | Start at 7.5 mg once daily; monitor renal function |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DARIFENACIN (DARIFENACIN).
| Breastfeeding | Unknown if darifenacin is excreted in human milk. M/P ratio not established. Due to potential anticholinergic effects in the infant (e.g., constipation, urinary retention), caution is advised; consider alternative therapy or avoid breastfeeding. |
| Teratogenic Risk | Pregnancy Category C. Darifenacin crosses the placenta. Animal studies show fetal toxicity at high doses, but no adequate human studies. First trimester: No confirmed human malformations; avoid unless benefit outweighs risk. Second/third trimester: Potential for reduced fetal growth; monitor fetal growth. Peripartum: Risk of neonatal anticholinergic effects (e.g., ileus, respiratory depression). |
■ FDA Black Box Warning
None.
| Serious Effects |
Urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, hypersensitivity to darifenacin or any component.
| Precautions | Use with caution in patients with clinically significant bladder outlet obstruction, gastrointestinal obstructive disorders, decreased gastrointestinal motility, severe hepatic impairment (Child-Pugh C), narrow-angle glaucoma, and myasthenia gravis. May cause angioedema, CNS effects (e.g., somnolence, dizziness), and QT prolongation. |
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| Fetal Monitoring | Monitor maternal anticholinergic side effects (dry mouth, constipation, blurred vision). Fetal ultrasound for growth parameters if used after 20 weeks. Assess neonatal adaptation at birth (respiratory, gastrointestinal function). |
| Fertility Effects | In animal studies, no significant impairment of fertility at clinically relevant doses. Human data insufficient to determine effects on fertility. Potential for anticholinergic-related sexual dysfunction (e.g., erectile dysfunction, reduced libido) in males. |