Long‐term treatment with darifenacin for overactive bladder: results of a 2‐year, open‐label extension study

Abstract

OBJECTIVE To examine, in a 2‐year, non‐comparative, open‐label extension study, the safety, tolerability and efficacy of darifenacin controlled‐release (CR) 7.5/15 mg once daily in patients with overactive bladder (OAB) who completed two 12‐week randomized, double‐blind, placebo‐controlled ‘feeder’ studies. PATIENTS AND METHODS Patients entering the extension received darifenacin 7.5 mg once daily for 2 weeks, after which a voluntary increase in dose to 15 mg was permitted. Thereafter, patients could adjust the dose (either 7.5 or 15 mg). Safety and tolerability were assessed from adverse events (AEs) and discontinuations. Efficacy was determined using various endpoints. RESULTS In all, 716 patients entered the extension (mean age 57.3 years; 85.1% women) and 475 (66.3%) completed it (1089.9 patient‐years of exposure). Darifenacin was well tolerated with no significant safety concerns. The most commonly reported AEs were dry mouth and constipation (all‐causality rates 23.3% and 20.9%, respectively), leading to discontinuation in 1.3% and 2.4% of patients, respectively. Constipation infrequently required intervention, and analysis of bowel‐habit questionnaires revealed that the reporting of constipation was related to minor changes in bowel habit rather than true constipation. The efficacy of darifenacin was maintained, including significant improvements in the number of incontinence episodes/week (median change −84.4% at 2 years, P < 0.001 vs feeder‐study baseline). After 2 years, >40% of patients achieved a ≥90% reduction in incontinence episodes/week. CONCLUSION In the first published 2‐year, open‐label study of a CR antimuscarinic agent, darifenacin 7.5/15 mg once daily had a favourable safety, tolerability and efficacy profile during the long‐term treatment of OAB. As such, darifenacin represents a valuable therapeutic option for OAB.

Initial combined treatment with anticholinergics and α-blockers for men with lower urinary tract symptoms related to BPH and overactive bladder: a prospective, randomized, multi-center, double-blind, placebo-controlled study

“…However, most previous clinical studies focused on either of the two symptoms. [12][13][14][15] These studies provided limited information on the associated LUTS secondary to BPH in patients with storage symptoms.…”

A review of adherence to drug therapy in patients with overactive bladder

“…Self reporting of medication adherence includes direct questioning and use of validated questionnaires, e.g. the medication adherence report scale (MARS), used to measure adherence to medication in OAB [7,8] Patients might claim to adhere to therapy to avoid disapproval from clinicians Third party estimates of adherence tend to overestimate patients' adherence [9] Return unused medication…”

“…There have been five longterm, open-label extensions of randomized controlled studies assessing adherence with oxybutynin, darifenacin tolterodine, solifenacin, and trospium [8][9][10][11][12]; the results are shown in Table 2.…”

Persistence of antimuscarinic drug use

“…Withdrawals during the short-term registration RCTs were few, and the results of long-term or open-label extension studies have also shown very good long-term persistence, e.g., a 1-year continuation rate of 75% for trospium chloride [6], a 40-week continuation rate of 81% for flexible-dose solifenacin [7], a 1-year continuation rate of 71% for tolterodine extended-release [8], and a 2-year continuation rate of 66% for darifenacin [9]. However, the external validity of these findings has been questioned by the somewhat more somber findings of real-life prescription refill behavior.…”