Toviaz (fesoterodine): Muscarinic receptor antagonist approved for the treatment of overactive bladder

New molecular entity: Fesoterodine (Toviaz), a muscarinic receptor antagonist, was approved on October 31, 2008, for the treatment of overactive bladder

Fesoterodine is a competitive muscarinic receptor antagonist that produces its effects by inhibiting the receptors that affect urinary bladder smooth muscle contractions. This agent was approved on October 31, 2008, for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

Efficacy. The efficacy of fesoterodine was assessed in two phase 3, randomized, double-blind, placebo-controlled, 12-week trials. Patients were randomized to treatment with fesoterodine 4 or 8 mg/d or placebo. In 1 study, 290 patients were randomized to an active control arm using an oral antimuscarinic agent. Between the 2 studies, 554 patients were treated with fesoterodine 4 mg/d, 566 were treated with fesoterodine 8 mg/d, and 554 were treated with placebo. The primary end points were mean change in the number of urge urinary incontinence episodes per 24 hours and mean change in the number of micturitions per 24 hours. In Study 1, fesoterodine-treated patients demonstrated statistically significant reductions versus placebo-treated patients in the number of urge incontinence episodes per 24 hours (fesoterodine 4 mg/d, –2.06; fesoterodine 8 mg/d, –2.27; placebo, –1.20; P≤.001) and in the number of micturitions per 24 hours (fesoterodine 4 mg/d, –1.74; fesoterodine 8 mg/d, –1.94; placebo, –1.02; P<.001). In Study 2, fesoterodine-treated patients demonstrated statistically significant reductions versus placebo-treated patients in the number of urge incontinence episodes per 24 hours (fesoterodine 4 mg/d, –1.77; fesoterodine 8 mg/d, –2.42; placebo, –1.00; P<.003 and P<.001 vs placebo, respectively) and in the number of micturitions per 24 hours (fesoterodine 4 mg/d, –1.86; fesoterodine 8 mg/d, –1.94; placebo, –1.02; P=.032 and P<.001 vs placebo, respectively). In both studies, the number of urge urinary incontinence episodes per 24 hours was reduced as early as 2 weeks after initiation of fesoterodine therapy.

Safety. Fesoterodine should be used cautiously in patients with clinically significant bladder outlet obstruction as these patients are at increased risk of urinary retention. This agent should also be used cautiously in patients with decreased gastrointestinal motility, controlled narrow-angle glaucoma, or myasthenia gravis. The most common adverse events associated with fesoterodine treatment include dry mouth, constipation, urinary tract infection, dry eyes, upper respiratory tract infection, and dyspepsia.