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solifenacin (Vesicare)

Tradenames: Vesicare (scheduled for release late 2004) Indications: - urinary frequency, urinary urgency due to overactive bladder, urge incontinence Contraindications: - use caution in patients with a) narrow-angle glaucoma b) gastroparesis & diminished peristalsis c) obstructive uropathy d) hepatic insufficiency e) renal insufficiency Dosage: 5-10 mg PO QD (no dose adjustment in the elderly) [4] Pharmacokinetics: 1) absorption not affected by food 2) peak plasma levels 3-8 hours after oral dose 3) absolute bioavailability is 90% 4) steady-state plasma levels 32-63 ng/mL for 5 & 10 mg QD 5) 98% bound to plasma proteins, mainly orosomucoid 6) volume of distribution 600 L 7) metabolized in liver primarily by cyt P450 3A4 8) 4R-hydroxy solifenacin, active metabolite, unlikely to contribute significant pharmacologic activity 9) elimination 1/2life is 45-68 hours with chronic dosing - t1/2 is 20-25% longer in elderly 10) 62% recovered in urine (< 15% unchanged), 22% in feces Dosage adjustment in renal failure: - maximum dose 5 mg QD for creatinine clearance < 30 mL/min Dosage adjustment with hepatic insufficiency - maximum dose 5 mg QD for moderate hepatic impairment (Child-Pugh B) - avoid with severe hepatic impairment (Child-Pugh C) Adverse effects: (% for 10 mg QD) 1) less drowsiness & dizziness than other anticholinergics 2) xerostomia 28% 3) constipation 9-13% - fecal impaction, intestinal obstruction 4) dyspepsia 4% 5) blurry vision 5% 6) may increase QT interval [3] 7) case of angioneurotic edema reported Drug interactions: - drugs that inhibit cyt P450 3A4 may increase 1/2life of solifenacin - max dose of solifenacin 5 mg QD when coadministered with ketoconazole or other potent inhibitor of cyt P450 3A4 - drugs that induce cyt P450 3A4 may decrease 1/2life of solifenacin Mechanism of action: 1) muscarinic M3 receptor antagonist 2) allegedly more selective for the muscarinc M3 receptor than other agents

Interactions

drug interactions drug adverse effects of parasympatholytics

General

urinary antispasmodic

Properties

MISC-INFO: protein-binding 98% 1/2life 45-68 HOURS pregnancy-category C

Database Correlations

PUBCHEM correlations

References

  1. Prescriber's Letter 11(9): 2004 Detail-Document#: 200910 (subscription needed) http://www.prescribersletter.com
  2. Prescriber's Letter 12(2): 2005 Antimuscarinic Medications for Overactive Bladder Detail-Document#: 210209 (subscription needed) http://www.prescribersletter.com
  3. http://www.vesicare.com
  4. Erdem M & Chu FM Management of overactive bladder and urge urinary incontinence in the elderly patient. Am J Med 2006;119(3A):295
  5. Deprecated Reference

Component-of

mirabegron/solifenacin (Myrbetriq/Vesicare)