Safety and Tolerability of Solifenacin Add-on Therapy to α-Blocker Treated Men With Residual Urgency and Frequency

Weill Medical College of Cornell University, New York, New York 10065-4805, USA.
The Journal of urology (Impact Factor: 3.75). 12/2009; 182(6):2825-30. DOI: 10.1016/j.juro.2009.08.023
Source: PubMed

ABSTRACT VICTOR was a 12-week, double-blind, placebo controlled trial assessing the safety and tolerability of solifenacin plus tamsulosin in men with residual overactive bladder symptoms after tamsulosin monotherapy. Efficacy of solifenacin plus tamsulosin vs placebo plus tamsulosin was also evaluated.
A total of 398 men 45 years old or older were randomized to 12 weeks of solifenacin plus tamsulosin or placebo plus tamsulosin once daily. The study population had 8 or more micturitions per 24 hours and 1 or more urgency episode per 24 hours after taking tamsulosin for 4 or more weeks, a total International Prostate Symptom Score of 13 or greater, a Patient Perception of Bladder Condition score of 3 or greater, a post-void residual of 200 ml or less and a peak flow rate of 5 ml per second or greater. Adverse events were monitored throughout the study. The primary efficacy end point was mean change from baseline to week 12 in micturitions per 24 hours. Secondary measures included mean change in urgency episodes per 24 hours, and changes in Patient Perception of Bladder Condition, Urgency Perception Scale and total International Prostate Symptom Scores.
The most frequent adverse events in the solifenacin plus tamsulosin and placebo plus tamsulosin groups were dry mouth (7% and 3%, respectively) and dizziness (3% and 2%, respectively). Of the patients on solifenacin plus tamsulosin 7 (3%) reported retention and 3 required catheterization. No patients on placebo plus tamsulosin reported retention. Patients on solifenacin plus tamsulosin vs placebo plus tamsulosin showed larger reductions in frequency but not of statistical significance (-1.05 vs -0.67, p = 0.135). However, patients on solifenacin plus tamsulosin vs placebo plus tamsulosin did show statistically significant reductions in urgency (-2.18 vs -1.10, p <0.001). Patient reported outcome measures showed no significant between group differences.
Solifenacin plus tamsulosin was well tolerated. There was a low incidence of urinary retention requiring catheterization. At week 12 solifenacin plus tamsulosin decreased daily micturitions and urgency episodes. Only urgency reached statistical significance vs placebo plus tamsulosin.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimsTo compare the therapeutic effects and identify predictors of successful treatment of first-line antimuscarinic and α-blocker monotherapy for men with predominant storage lower urinary tract symptoms (LUTS).Methods This prospective randomised comparative study included men aged ≥ 40 years with a total IPSS ≥ 8, IPSS storage subscore (IPSS-S) ≥ voiding subscore (IPSS-V) and PVR ≤ 250 ml. Subjects were randomised to receive tolterodine 4 mg or doxazosin 4 mg daily for 12 weeks. The primary end-point included changes of total IPSS, IPSS subscore and global response assessment (GRA) after treatment. The secondary end-points included comparisons of baseline parameters between patients with a GRA ≥ 1 and GRA < 1. All adverse events were also recorded.ResultsThis study was completed by 163 patients. The IPSS-T, IPSS-S and quality of life index decreased significantly in both groups. An improved outcome (GRA ≥ 1) at 4 weeks was reported in 51/74 patients (68.9%) receiving doxazosin and 69/89 patients (77.5%) receiving tolterodine. The rate of improved outcome in patients with a TPV < 40 ml was significantly higher in tolterodine group (73.3% vs. 57.6%, p = 0.040). Patients with tolterodine treatment failure (GRA < 1) had higher baseline IPSS-V and IPSS intermittency domain, whereas patients with doxazosin treatment failure had a higher baseline IPSS urgency domain.Conclusions The rate of improved outcome was comparable between first-line tolterodine and doxazosin monotherapy for male storage LUTS. Antimuscarinic monotherapy was suggested for men with smaller prostate volume and higher urgency symptom scores, whereas α-blocker monotherapy was suggested for those with higher voiding symptom scores.
    International Journal of Clinical Practice 12/2014; 69(1). DOI:10.1111/ijcp.12488 · 2.54 Impact Factor
  • Current Bladder Dysfunction Reports 12/2014; 9(4):372-378. DOI:10.1007/s11884-014-0263-6
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Men reporting mixed storage and voiding lower urinary tract symptoms (LUTS) often experience persisting storage LUTS after initial treatment. Combination therapy of an alfa-adrenergic antagonist and an antimuscarinic is increasingly recognized as a therapy option. Clinical trials have combined tamsulosin (0.4 mg) with different doses of solifenacin. In the SATURN study, greater efficacy benefits were observed for moderate to severe storage symptoms. Single tablet administration may offer improved compliance. Accordingly, the NEPTUNE study researched fixed-dose combination (FDC) therapy for mixed LUTS, using tamsulosin (oral controlled administration system formulation), with solifenacin (6 or 9 mg). The FDC containing tamsulosin and solifenacin 6 mg improved storage and voiding LUTS, with no additional benefit from the higher solifenacin dose. During the open-label extension study, symptom improvement was maintained. Adverse events reflected the known effects of the component therapies. Acute urinary retention, an adverse event of special interest, was seen in only a small number of treated men.
    Drugs of Today 12/2014; 50(12):803-811. DOI:10.1358/dot.2014.50.12.2247444


Available from