Introduction
Solifenacin succinate is an antimuscarinic medication primarily used in the management of overactive bladder (OAB) syndrome. As a quaternary ammonium compound, it belongs to the class of anticholinergic agents that selectively target muscarinic receptors in the bladder. First approved by the FDA in 2004, solifenacin has become a well-established treatment option for urinary symptoms associated with detrusor overactivity.
Mechanism of Action
Solifenacin functions as a competitive muscarinic receptor antagonist with particular affinity for the M3 receptor subtype. These receptors are predominantly located in the urinary bladder detrusor muscle and salivary glands. By blocking acetylcholine binding at muscarinic receptors, solifenacin reduces involuntary detrusor contractions during the bladder filling phase, increases bladder capacity, decreases urinary urgency, and reduces urinary frequency. Its relative selectivity for M3 receptors over M2 receptors may contribute to its favorable side effect profile compared to non-selective antimuscarinic agents.
Indications
- Treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency
- Management of neurogenic detrusor overactivity (off-label use in some regions)
- Nocturnal enuresis associated with overactive bladder (off-label use)
Dosage and Administration
Standard dosing:- Initial dose: 5 mg orally once daily
- May increase to 10 mg once daily if 5 mg dose is well-tolerated but inadequate response
- Maximum dose: 10 mg daily
- Renal impairment: Maximum dose 5 mg daily for severe impairment (CrCl <30 mL/min)
- Hepatic impairment: Maximum dose 5 mg daily for moderate impairment (Child-Pugh B)
- Severe hepatic impairment (Child-Pugh C): Not recommended
- Geriatric patients: No dosage adjustment required based on age alone
- Pediatric patients: Safety and effectiveness not established
- Take with water and swallow whole
- May be taken with or without food
- Avoid crushing or chewing tablets
Pharmacokinetics
Absorption: Well absorbed with oral bioavailability approximately 90% Distribution: Volume of distribution ~600 L, extensively bound to plasma proteins (98%), primarily α-1-acid glycoprotein Metabolism: Primarily hepatic metabolism via CYP3A4 with minor contributions from CYP2C19 and CYP2C9 Elimination: Terminal half-life approximately 45-68 hours, excreted primarily in urine (69%) and feces (22%) as metabolites Time to peak concentration: 3-8 hours post-dose Steady-state: Achieved within 1 week of daily dosingContraindications
- Urinary retention
- Gastric retention
- Uncontrolled narrow-angle glaucoma
- Hypersensitivity to solifenacin or any component of the formulation
- Myasthenia gravis
- Severe hepatic impairment (Child-Pugh C)
Warnings and Precautions
Boxed Warning: None- Angioedema: Reports of angioedema involving face, lips, tongue, and/or larynx
- QT prolongation: Avoid in patients with known QT prolongation or taking other QT-prolonging drugs
- Cognitive effects: May cause confusion, hallucinations, and somnolence, particularly in elderly patients
- Heat prostration: May occur in hot environments due to decreased sweating
- Urinary retention: May occur in patients with bladder outlet obstruction
- Gastrointestinal motility disorders: Use with caution in patients with decreased gastrointestinal motility
- Renal/hepatic impairment: Dose adjustment required
- Pregnancy: Category C - use only if potential benefit justifies potential risk
- Lactation: Excreted in breast milk - not recommended during breastfeeding
Drug Interactions
Strong CYP3A4 inhibitors: (ketoconazole, clarithromycin) - Maximum solifenacin dose 5 mg daily Other CYP3A4 inhibitors: (erythromycin, fluconazole) - Use with caution QT-prolonging drugs: (Class IA/III antiarrhythmics, macrolides) - Increased risk of QT prolongation Other anticholinergic agents: Additive anticholinergic effects Cholinergic agonists: May antagonize effects Digoxin: Monitor digoxin levels (solifenacin may increase concentrations)Adverse Effects
Common (≥1%):- Dry mouth (11-27%)
- Constipation (5-13%)
- Blurred vision (4-7%)
- Dyspepsia (3-4%)
- Nausea (2-3%)
- Urinary tract infection (2-3%)
- Dry eyes (1-2%)
- Angioedema
- QT prolongation
- Urinary retention
- Acute narrow-angle glaucoma
- Severe constipation leading to intestinal obstruction
- Cognitive impairment including confusion and hallucinations
- Torsades de pointes (rare)
Monitoring Parameters
- Symptom improvement (voiding diary, incontinence episodes)
- Post-void residual volume in at-risk patients
- Cognitive function in elderly patients
- Intraocular pressure in glaucoma patients
- Electrolytes and ECG in patients at risk for QT prolongation
- Renal and hepatic function periodically
- Signs of urinary retention or gastrointestinal hypomotility
- Adverse effects assessment at each follow-up visit
Patient Education
- Take medication exactly as prescribed at the same time each day
- Report immediately: swelling of face/lips/tongue, difficulty breathing, eye pain with vision changes
- May cause dry mouth - sugar-free gum/candies or saliva substitutes may help
- Maintain adequate fluid intake to prevent constipation
- May cause blurred vision - use caution when driving or operating machinery
- Avoid excessive heat exposure due to reduced sweating capacity
- Inform all healthcare providers about solifenacin use
- Do not stop medication abruptly without consulting prescriber
- Report any new medications to prescriber due to interaction potential
- Regular follow-up appointments are important for monitoring effectiveness and side effects
References
1. Chapple CR, et al. Eur Urol. 2004;46(3):376-380 2. Cardozo L, et al. BJU Int. 2004;94(6):817-822 3. VESIcare® (solifenacin succinate) prescribing information. Astellas Pharma US, Inc. 4. Michel MC, et al. Drugs. 2008;68(2):251-268 5. Novara G, et al. Eur Urol. 2008;54(4):740-764 6. Wagg A, et al. Drugs Aging. 2013;30(10):809-821 7. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Solifenacin monograph 8. UpToDate. Solifenacin: Drug information. Wolters Kluwer Health