An investigation of dose titration with darifenacin, an M₃‐selective receptor antagonist

Abstract

electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse-event reports. RESULTSThe treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at -8.2 ( -62.9%) and -6.0 ( -48.1%), respectively ( P = 0.035). There were also significant improvements in voiding frequency ( P = 0.001), bladder capacity (volume voided; P = 0.036), frequency of urgency ( P < 0.001), severity of urgency ( P = 0.013) and number of significant leaks/ week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for 'sensitive' patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatmentrelated adverse events were mild-tomoderate dry mouth and constipation, which led to discontinuation in < 3.0% of darifenacin-treated patients and < 1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo.

Long‐term benefits of darifenacin treatment for patient quality of life: Results from a 2‐year extension study

“…treatment with darifenacin 3.75, 7.5, or 15 mg, or matching placebo. 16,17 Details of the design and methodology for the extension study have previously been reported elsewhere. 13 During the open-label extension, patients received darifenacin 7.5 mg (irrespective of feeder-study dose) for the first 2 weeks, followed by individualized dose adjustments (7.5 or 15 mg o.d.)…”

“…13 As in the feeder studies, the use of concomitant medications (such as anticholinergic/antispasmodic drugs, opioids and other drugs known to cause constipation) was restricted, and patients taking potent inhibitors of cytochrome P450 3A4 were required to receive a maximum dose of 7.5 mg darifenacin. In addition, patients with clinically significant hepatic impairment or moderate hepatic impairment (ChildPugh B) 16,17 were excluded. Changes in the active management of OAB (such as introduction of a bladder training program) were not permitted during this study.…”

“…Patients (male or female) were enrolled in the extension study if they had successfully completed one of two previous feeder studies 16,17 with no major protocol violation. These were adults (!18 years) with a history of symptoms of 'wet' OAB (urgency, urinary incontinence, frequency) for at least 6 months, and capable of independent toileting and completion of patient diaries.…”

772 Adverse Event Assessment of Antimuscarinics for Treating Overactive Bladder: A Network Meta-Analytic Approach

“…Three articles [19][20][21] not specifying adverse events, one article [22] not differentiating adverse events between antimuscarinic and placebo, six articles [23][24][25][26][27][28] not discriminating adverse events between different fixed dosages, and three articles [29][30][31] only comparing different releases within the same antimuscarinic and dosage were excluded. Thus, we finally included 69 trials including one report [66] with two different age strata ( Table 2, Data S2).…”

Darifenacin: first M3 receptor antagonist for overactive bladder

“…12 In the pooled analysis, a total of 1059 patients (85 per cent women, 95 per cent idiopathic OAB) with frequency, urgency and urge incontinence of at least six months' duration were randomised to placebo or darifenacin 7.5 or 15mg per day. The primar y end-point was the median change in number of incontinence episodes per week.…”