Introduction
Darifenacin is an antimuscarinic medication specifically developed for the treatment of overactive bladder (OAB) syndrome. As a once-daily extended-release formulation, it offers selective inhibition of the M3 muscarinic receptor subtype, which is primarily responsible for detrusor muscle contraction. This targeted mechanism provides effective relief from OAB symptoms while potentially minimizing systemic anticholinergic effects.
Mechanism of Action
Darifenacin functions as a competitive muscarinic receptor antagonist with high specificity for the M3 receptor subtype. In the urinary bladder, M3 receptors mediate acetylcholine-induced detrusor muscle contraction. By blocking these receptors, darifenacin reduces involuntary bladder contractions, increases bladder capacity, decreases urinary urgency, and reduces frequency of micturition. Its selectivity for M3 over other muscarinic receptor subtypes (particularly M1, M2, and M4) may contribute to a more favorable side effect profile compared to non-selective antimuscarinic agents.
Indications
Darifenacin is FDA-approved for the treatment of overactive bladder with symptoms of:
- Urge urinary incontinence
- Urgency
- Frequency
It is indicated for adults who have not responded adequately to behavioral modifications alone.
Dosage and Administration
Standard dosing:- Initial dose: 7.5 mg orally once daily
- May be increased to 15 mg once daily after two weeks if needed
- Should be taken with water and swallowed whole; not to be chewed, crushed, or divided
- Hepatic impairment: Maximum 7.5 mg daily for moderate impairment (Child-Pugh B); contraindicated in severe impairment (Child-Pugh C)
- Renal impairment: No dosage adjustment needed for mild to moderate impairment; use with caution in severe impairment
- Geriatric patients: No dosage adjustment required based on age alone
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability approximately 15-19%; peak plasma concentrations reached within 7 hours; food does not significantly affect absorption Distribution: Volume of distribution ~163 L; extensively bound to plasma proteins (98%, primarily α1-acid glycoprotein) Metabolism: Primarily metabolized by CYP3A4 and CYP2D6 isoenzymes via oxidative metabolism; major metabolites are minimally pharmacologically active Elimination: Terminal half-life ~13-19 hours; excreted primarily in feces (60%) and urine (40%) as metabolites; less than 3% excreted unchangedContraindications
- Urinary retention
- Gastric retention
- Uncontrolled narrow-angle glaucoma
- Hypersensitivity to darifenacin or any component of the formulation
- Severe hepatic impairment (Child-Pugh C)
Warnings and Precautions
Urinary Retention: May occur in patients with bladder outlet obstruction; use with caution Gastrointestinal Disorders: May decrease gastrointestinal motility; use caution in patients with gastrointestinal obstructive disorders Controlled Narrow-Angle Glaucoma: Use only if potential benefits outweigh risks QT Prolongation: May cause dose-dependent QT interval prolongation; use caution in patients with known QT prolongation or taking other QT-prolonging drugs Cognitive Effects: May cause blurred vision, drowsiness, or dizziness; caution patients about driving or operating machinery Heat Prostration: May occur in hot environments due to decreased sweating Myasthenia Gravis: May exacerbate symptomsDrug Interactions
Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir): May increase darifenacin concentrations; maximum dose should not exceed 7.5 mg daily Other anticholinergic agents: May increase anticholinergic adverse effects QT-prolonging drugs: May have additive effects on QT interval Drugs metabolized by CYP2D6: Darifenacin may inhibit CYP2D6; monitor drugs with narrow therapeutic indices (flecainide, thioridazine, tricyclic antidepressants)Adverse Effects
Common (≥2%):- Dry mouth (20.2%)
- Constipation (14.8%)
- Dyspepsia (4.0%)
- Nausea (2.6%)
- Abdominal pain (2.4%)
- blurred vision (2.0%)
- Urinary retention
- Angioedema
- QT prolongation
- Confusion (particularly in elderly)
- Heat stroke
Monitoring Parameters
- Symptom improvement (voiding diary: frequency, urgency, incontinence episodes)
- Post-void residual volume (in patients at risk for urinary retention)
- Constipation symptoms and management
- Visual changes
- Cognitive function in elderly patients
- Hepatic function in patients with pre-existing impairment
- Electrolytes and ECG in patients at risk for QT prolongation
Patient Education
- Take medication exactly as prescribed; do not crush or chew tablets
- Report any difficulty urinating, eye pain, or vision changes immediately
- Maintain adequate fluid intake to prevent constipation
- Be aware that decreased sweating may increase risk of heat-related illness
- Use caution when driving or operating machinery until effects are known
- Inform all healthcare providers about darifenacin use
- Do not stop medication abruptly without consulting your physician
- Allow 4-8 weeks for full therapeutic effect
- Consider pelvic floor exercises and behavioral modifications as adjunct therapies
References
1. Chapple CR, et al. Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol. 2004;45(4):420-429. 2. Haab F, et al. Darifenacin, an M3 selective receptor antagonist, improves symptoms of overactive bladder in patients with detrusor overactivity. BJU Int. 2004;94(6):817-820. 3. Darifenacin [package insert]. Novartis Pharmaceuticals Corporation; 2021. 4. Andersson KE. Antimuscarinic mechanisms and the overactive detrusor: an update. Eur Urol. 2011;59(3):377-386. 5. Nitti VW, et al. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol. 2013;189(4):1388-1395. 6. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2023. Darifenacin.