Solifenacin Succinate (VESicare)
By William T. Elliott, MD, FACP and James Chan, PharmD, PhD
Solifenacin succinate has been approved for the treatment of overactive bladder, the third new agent to be approved for this indication in the last 7 months. Solifenacin may be the most bladder specific muscarinic receptor antagonist currently available. The drug is manufactured by Yamanouchi Pharma Technologies Inc in Norman Oklahoma and will be marketed by Yamanouchi Pharma America and GlaxoSmithKline as VESicareTM.
Solifenacin is indicated for the treatment of overactive bladder with symptoms of urge incontinence, urgency, and urinary frequency.1
The recommended starting dose is 5 mg once daily. The dose may be increased to 10 mg once daily if tolerated. For patients with moderate hepatic impairment or severe renal impairment, or in patients with receiving concomitant administration of a potent CYP3A4 inhibitor, the dose should not exceed 5 mg once daily.
Solifenacin is not recommended for patients with severe hepatic impairment.1 In contrast, drugs that are CYP3A4 inducers may reduce the effect of solifenacin.
Solifenacin appears to be more M3 receptor subtype selective for bladder smooth muscle than salivary gland compared to oxybutynin, tolterodine, or darifenacin.2
Most common side effects are dry mouth (10.9%-27.6% vs 4.2 % for placebo) and constipation (5.4%-13.4% vs 2.9%).1
Solifenacin was evaluated in 4 12-week, double-blind, randomized, placebo-controlled trials.1,3 The drug showed a reduction in number of micturitions/24 hours, reduction in number of urge incontinence episodes/24 hours, and an increase in void volume per micturition. Solifenacin 5 mg and 10 mg showed statistically significant placebo subtracted difference in the reduction in number of micturitions/24 hours of 0.7 to 1.5, reduction in the number of incontinence episodes/24 hours of 0.3 to 0.9, and increase in volume per micturition of 25.5 mL to 44.5 mL. Solifenacin 10 mg daily showed a statistically significant decrease in nocturia by 0.73 compared to 0.52 for placebo. The 5-mg dose did not reach statistical significance.3 In a dose-finding, active-controlled study, tolterodine (2 mg twice daily) showed a smaller increase in volume voided and a smaller decrease in the frequency of daily voids, but an insignificant difference in the number of incontinent episodes.4 However the number of subjects randomized to each arm was relatively small (35-41). Solifenacin has an extremely long half-life (45-68 hours). The wholesale cost of solifenacin is $2.80 per day for both strengths.
Solifenacin is the newest antimuscarinic agent approved. While in vitro data suggest that it may be the most bladder specific M3 receptor antagonist clear clinical advantage has not been demonstrated. As with other drug of the class the effects are modest with a large placebo response.5,6
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
1. VESIcare Product Information. GlaxoSmithKline. November 2004.
2. Kobayashi S, et al. Life Sci. 2004;74(7):843-853.
3. Cardozo L, et al. J Urol. 2004;172:1919-1924.
4. Chapple CR, et al. BJU Int. 2004;93:303-310.
5. Hay-Smith J, et al. Cochran Database Syst Rev. 2004.
6. Herbison P, et al. BMJ. 2003;326:841.