Introduction
VESIcare (solifenacin succinate) is an antimuscarinic agent specifically developed for the treatment of overactive bladder (OAB) syndrome. It is a once-daily oral medication that helps control urinary urgency, frequency, and urge incontinence by relaxing bladder smooth muscle. Approved by the FDA in 2004, VESIcare has become a cornerstone in OAB management due to its favorable efficacy and tolerability profile.
Mechanism of Action
VESIcare exerts its therapeutic effects through competitive inhibition of muscarinic receptors, particularly the M3 subtype, which is primarily responsible for bladder detrusor muscle contraction. By blocking acetylcholine binding at these receptors, solifenacin reduces involuntary bladder contractions, increases bladder capacity, and decreases urinary urgency. The drug demonstrates selectivity for urinary bladder receptors over salivary glands, contributing to its improved dry mouth profile compared to older antimuscarinic agents.
Indications
VESIcare is indicated for the treatment of:
- Overactive bladder with symptoms of urge urinary incontinence
- Urgency
- Frequency
It is approved for use in adults and pediatric patients 2 years of age and older.
Dosage and Administration
Standard dosing:- Adults: 5 mg orally once daily
- May increase to 10 mg once daily if needed
- 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): Use not recommended
- Geriatric patients: Dose adjustment based on renal/hepatic function
- Pediatric patients (2 years and older): Weight-based dosing (refer to prescribing information)
- Take with water and swallow whole
- May be taken with or without food
- Avoid crushing or chewing tablets
Pharmacokinetics
Absorption: Solifenacin is well absorbed with approximately 90% bioavailability. Peak plasma concentrations occur 3-8 hours after oral administration. Food does not significantly affect absorption. Distribution: Volume of distribution is approximately 600 L. Plasma protein binding is approximately 98%, primarily to alpha-1-acid glycoprotein. Metabolism: Primarily metabolized by CYP3A4 hepatic enzymes. The major metabolic pathway involves N-oxidation, with minor pathways including N-dealkylation and 4R-hydroxysolifenacin formation. Elimination: Terminal half-life is approximately 45-68 hours. Excretion occurs primarily in feces (approximately 69%) and urine (approximately 23%) as metabolites. Less than 15% is excreted unchanged.Contraindications
- Urinary retention
- Gastric retention
- Uncontrolled narrow-angle glaucoma
- Hypersensitivity to solifenacin succinate or any component of the formulation
- Myasthenia gravis
Warnings and Precautions
Angioedema: Rare cases of angioedema involving face, lips, tongue, and/or larynx have been reported. QT Prolongation: Avoid use in patients with known QT prolongation or those taking medications that prolong QT interval. Cognitive Effects: CNS anticholinergic effects including confusion, hallucinations, and somnolence have been reported, particularly in elderly patients. Renal/Hepatic Impairment: Use with caution and dose adjustment required. Heat Proliferation: May decrease sweating, leading to heat exhaustion in hot environments. Urinary Retention: May occur in patients with bladder outlet obstruction. GERD: May exacerbate gastroesophageal reflux disease.Drug Interactions
Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin): Increase solifenacin exposure - maximum dose 5 mg daily Other anticholinergic agents: Increased anticholinergic adverse effects QT-prolonging drugs (Class IA/III antiarrhythmics, macrolides): Increased risk of QT prolongation Cholinergic agonists: May decrease efficacy Digoxin: Monitor digoxin levels when initiating solifenacinAdverse Effects
Common (≥2%):- Dry mouth (11-27%)
- Constipation (5-13%)
- Blurred vision (4-6%)
- Urinary tract infection (3-5%)
- Dry eyes (2-4%)
- Dyspepsia (2-3%)
- Nausea (2-3%)
- Angioedema
- QT prolongation
- Urinary retention
- Anaphylactic reactions
- Hallucinations
- Delirium
Monitoring Parameters
- Symptom improvement (voiding diary)
- Post-void residual volume in at-risk patients
- Renal and hepatic function at baseline and periodically
- Intraocular pressure in glaucoma patients
- Cognitive function in elderly patients
- Constipation and bowel function
- Signs of urinary retention
- Electrolytes in patients at risk for QT prolongation
Patient Education
- Take medication at the same time each day
- Report any difficulty urinating or complete inability to urinate
- Use caution when driving or operating machinery until effects are known
- Maintain adequate fluid intake to prevent constipation
- Avoid excessive heat exposure due to reduced sweating capacity
- Chew sugar-free gum or use saliva substitutes for dry mouth
- Report vision changes or eye pain immediately
- Inform all healthcare providers about VESIcare use
- Do not stop medication abruptly without consulting prescriber
- Store at room temperature away from moisture and heat
References
1. Chapple CR, et al. Solifenacin significantly improves all symptoms of overactive bladder syndrome. Int J Clin Pract. 2006;60(8):959-966. 2. VESIcare® (solifenacin succinate) prescribing information. Astellas Pharma US, Inc. 2022. 3. Abrams P, et al. Solifenacin is effective for the treatment of OAB dry patients: a pooled analysis. Eur Urol. 2005;48(3):483-487. 4. Michel MC, et al. Cardiovascular safety of solifenacin in subjects with overactive bladder syndrome. Am J Cardiol. 2010;105(5):672-676. 5. Wagg A, et al. Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis. Am J Geriatr Pharmacother. 2006;4(1):14-24. 6. Novara G, et al. A systematic review and meta-analysis of randomized controlled trials with antimuscarinic drugs for overactive bladder. Eur Urol. 2008;54(4):740-764.