Darifenacin

Five RCTs compared darifenacin (3.75 – 30mg/day) with placebo. Two RCTs compared darifenacin (2.5mg TID – 30mg/day) with oxybutynin (2.5 – 5mg TID) and one RCT compared darifenacin (15mg/day) with tolterodine (2 mg BID). The RCTs varied in duration from 1 – 12 weeks. Four of five placebo controlled trials reported a statistically significant reduction in the median number of incontinence episodes with darifenacin (1.4 to 4.3 fewer episodes/week vs placebo). Three reported a statistically significant reduction in median voiding frequency with darifenacin (0.7 to 0.9 fewer episodes/day vs placebo). RCTs comparing darifenacin with oxybutynin or tolterodine demonstrated no difference in efficacy.

As for other anti-cholinergic drugs, darifenacin significantly increased dry mouth and constipation compared with placebo. It increased the incidence of constipation compared with tolterodine, but decreased the incidence of dry mouth compared with oxybutynin.

Solifenacin

Three (4 – 12 week) RCTs compared solifenacin (2.5 – 10 mg/day) with tolterodine (2 – 4mg BID). Two (4 – 12 week) RCTs compared solifenacin (2.5 – 10mg/day) with placebo. One active comparator RCT found statistically significantly fewer episodes of incontinence (mean reduction of 0.49 episodes/day for solifenacin vs tolterodine) and improvements in quality of life as measured by perception of bladder condition scale (mean difference 0.18 points on a total score of 6 points favouring solifenacin over tolterodine). The other two RCTs found a statistically significant difference only for urgency episodes (0.43 to 1.02 fewer episodes/day), favouring solifenacin over tolterodine. However, in all three RCTs solifenacin increased the incidence of constipation as compared with tolterodine.

Trospium

There were 12 RCTs of trospium (8 of trospium 10 – 40mg BID vs placebo, 3 of trospium 20mg BID vs oxybutynin 5mg BID and one of trospium 20mg BID vs placebo and tolterodine 2mg BID). Nine RCTs were of 2 – 4 weeks duration, and seven used urodynamic outcome measures. The Common Drug Review focused on two 12-week placebo controlled RCTs and one 52-week RCT comparing trospium 20mg BID with oxybutynin 5mg BID, all of which reported clinical outcome measures. Trospium was superior to placebo and equivalent to oxybutynin as assessed by the episodes of urge incontinence and voids per day. In the two placebo-controlled RCTs, trospium reduced daily voids by 2.4 – 3/day (from a baseline of 13/day), compared with a reduction of 0.6–1.8/day with placebo. Trospium significantly increased dry mouth and constipation, compared with placebo. At the above doses, trospium decreased incidence of dry mouth compared with oxybutynin, but not compared with tolterodine.

Darifenacin: Do not list

• “CEDAC recommends that darifenacin not be listed.”
• “There is insufficient evidence in support of an advantage of darifenacin over … other agents [oxybutynin, tolterodine or trospium].”²

Solifenacin: Do not list

• “CEDAC recommends that solifenacin not be listed.”
• “There is insufficient evidence that solifenacin provides clinically important differences in outcomes compared to less expensive alternatives.”
• “Overactive bladder is most commonly observed in older populations, who are most susceptible to anticholinergic adverse effects. The long serum half-life (approximately 60 hours) and accumulation of solifenacin in patients with chronic kidney disease, increases the possibility of prolonged adverse drug events, especially in patients with impaired renal function.”³

Trospium chloride: List with criteria/condition

• “CEDAC recommends that trospium be listed for patients who cannot tolerate immediate-release oxybutynin and in a similar manner as drug plans list tolterodine.”⁴

General Concerns of CEDAC

The CEDAC committee had concerns about the increase in number of anticholinergic agents available to treat overactive bladder disorder, the increased use of these agents and the risk to benefit ratio, especially in elderly patients. The committee recommended that the drug plans consider a drug class review of the effectiveness, safety and cost-effectiveness of these agents.