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Solifenacin: pharmacology and clinical efficacy Expert Rev. Clin. Pharmacol. 2(3), 239–253 (2009)
Dudley Robinson† and Linda Cardozo † Author for correspondence 3rd Floor, Golden Jubilee Wing, King’s College Hospital, London, UK Tel.: +44 203 299 3568 Fax: +44 203 299 3449 [email protected]
While antimuscarinic drug therapy has been proven to be effective in the management of patients with symptoms of overactive bladder syndrome, compliance and persistence with medication is often affected by the bothersome antimuscarinic adverse effects of dry mouth, constipation, somnolence and blurred vision. The development of bladder-selective M3-specific antagonists, such as solifenacin, has introduced the possibility of increasing efficacy while minimizing adverse effects. This article will review the preclinical and clinical data surrounding the development of solifenacin as well as providing an overview of the extensive body of evidence supporting its use in the management of patients with overactive bladder syndrome. Keywords : antimuscarinics • detrusor overactivity • overactive bladder • solifenacin • urinary incontinence
Urinary incontinence, the ‘complaint of any involuntary leakage of urine’ [1] is a common and distressing condition known to adversely affect quality of life [2] . Antimuscarinic drug therapy, in conjunction with behavioral therapy, such as bladder retraining, remains the first-line management of patients with symptoms suggestive of overactive bladder (OAB) syndrome. Drug treatment continues to be have an important role in the management of women with urinary incontinence, although from the number of preparations studied it is clear that there are no ideal drugs and very often the clinical results have been disappointing, this being partly due to poor efficacy and side effects [3] . Comparison of drug therapies for incontinence is compounded by a placebo effect of 30–40% and since the response to any drug is only likely to be in the region of 60%, any differences detected are likely to be small and thus require large-scale studies to demonstrate an effect. The clinical effectiveness of antimuscarinic agents in the treatment of OAB has also been questioned in a systematic review of 32 trials including 6800 participants [4] . Following treatment with antimuscarinic drugs, cure or improvement (relative risk: 1.41; 95% CI: 1.29–1.54), incontinence episode frequency per 24 h (mean difference: 0.6; 95% CI: 0.4–0.8), number of voids per 24 h (mean difference: 0.6; 95% CI: 0.4– 0.8), maximum cystometric capacity (mean difference: 54 ml; 95% CI: 43–66 ml), and volume at first contraction (mean difference: www.expert-reviews.com
10.1586/ECP.09.3
52 ml, 95% CI: 37–67 ml) were all significantly in favor of antimuscarinic therapy (p
Solifenacin: pharmacology and clinical efficacy Expert Rev. Clin. Pharmacol. 2(3), 239–253 (2009)
Dudley Robinson† and Linda Cardozo † Author for correspondence 3rd Floor, Golden Jubilee Wing, King’s College Hospital, London, UK Tel.: +44 203 299 3568 Fax: +44 203 299 3449 [email protected]
While antimuscarinic drug therapy has been proven to be effective in the management of patients with symptoms of overactive bladder syndrome, compliance and persistence with medication is often affected by the bothersome antimuscarinic adverse effects of dry mouth, constipation, somnolence and blurred vision. The development of bladder-selective M3-specific antagonists, such as solifenacin, has introduced the possibility of increasing efficacy while minimizing adverse effects. This article will review the preclinical and clinical data surrounding the development of solifenacin as well as providing an overview of the extensive body of evidence supporting its use in the management of patients with overactive bladder syndrome. Keywords : antimuscarinics • detrusor overactivity • overactive bladder • solifenacin • urinary incontinence
Urinary incontinence, the ‘complaint of any involuntary leakage of urine’ [1] is a common and distressing condition known to adversely affect quality of life [2] . Antimuscarinic drug therapy, in conjunction with behavioral therapy, such as bladder retraining, remains the first-line management of patients with symptoms suggestive of overactive bladder (OAB) syndrome. Drug treatment continues to be have an important role in the management of women with urinary incontinence, although from the number of preparations studied it is clear that there are no ideal drugs and very often the clinical results have been disappointing, this being partly due to poor efficacy and side effects [3] . Comparison of drug therapies for incontinence is compounded by a placebo effect of 30–40% and since the response to any drug is only likely to be in the region of 60%, any differences detected are likely to be small and thus require large-scale studies to demonstrate an effect. The clinical effectiveness of antimuscarinic agents in the treatment of OAB has also been questioned in a systematic review of 32 trials including 6800 participants [4] . Following treatment with antimuscarinic drugs, cure or improvement (relative risk: 1.41; 95% CI: 1.29–1.54), incontinence episode frequency per 24 h (mean difference: 0.6; 95% CI: 0.4–0.8), number of voids per 24 h (mean difference: 0.6; 95% CI: 0.4– 0.8), maximum cystometric capacity (mean difference: 54 ml; 95% CI: 43–66 ml), and volume at first contraction (mean difference: www.expert-reviews.com
10.1586/ECP.09.3
52 ml, 95% CI: 37–67 ml) were all significantly in favor of antimuscarinic therapy (p
