A closer look at new FDA actions: Toviaz
Pfizer Inc’s Toviaz (fesoterodine fumarate)
On October 31, 2008, the FDA approved the use of Toviaz (fesoterodine fumarate), a once-daily, extended-release tablet that has been clinically proven to reduce urinary urge, frequency, and incontinence in individuals experiencing symptoms of overactive bladder.1 The recommended starting dose for Toviaz is 4 mg, but may be increased to 8 mg, depending on the individual. Toviaz has only been approved for adults and has not yet been approved for pediatric use.1
Pharmacology and Pharmacokinetics
Toviaz is a competitive muscarinic receptor antagonist. Muscarinic receptors cause contractions of urinary bladder smooth muscle and also stimulate saliva secretion. After oral administration, Toviaz is rapidly hydrolyzed by nonspecific esterases to its active metabolite 5-hydroxymethyl tolterodine, which exhibits antimuscarinic effects. Toviaz is well-absorbed when taken orally, and food does not affect its absorption. Toviaz has low plasma protein binding, is primarily metabolized by the liver, and is excreted via the kidneys.2
A randomized, double-blind, placebocontrolled, multicenter trial was performed to determine the safety, efficacy, and tolerability of Toviaz. In the trial, 836 subjects with urinary frequency, urinary urgency, or urge urinary incontinence were randomized to placebo (n = 274), 4 mg fesoterodine (n = 283), or 8 mg fesoterodine (n = 279) once daily for 12 weeks.
The primary efficacy end point was the change in the number of micturitions per 24 hours. Coprimary end points were the change in the number of urge urinary incontinence episodes per 24 hours and the treatment response. Secondary efficacy end points were the change in mean voided volume per micturition and the number of continent days and urgency episodes per 24 hours. Tolerability and safety were assessed by evaluating adverse events, electrocardiograms, postvoid residual urine volume, laboratory parameters, and treatment withdrawals.
Treatment with 4- or 8-mg fesoterodine resulted in statistically significant improvements from baseline to end of treatment for the primary and coprimary end points compared with placebo (P <.05).
Results for most secondary end points, including mean voided volume per micturition, number of continent days, and number of urgency episodes per 24 hours, were also significantly improved versus placebo. The adverse events reported more frequently with fesoterodine than with placebo were dry mouth, constipation, and urinary tract infection.3
In patients with mild or moderate renal insufficiency, no dose adjustment is needed. In patients with severe renal insufficiency, doses of Toviaz greater than 4 mg are not recommended.2
No dose adjustments are necessary with mild-to-moderate hepatic dysfunction. Patients with severe hepatic dysfunction should not take Toviaz, whereas it has not been studied in this patient population.
The most common side effects observed with Toviaz include dry mouth and constipation. The incidence of dry mouth was higher in patients receiving Toviaz 8 mg/day (35%) and those receiving 4 mg/day (19%), compared with those receiving placebo (7%). The incidence of constipation was lower in those patients receiving placebo (2%), compared with 4% of those taking Toviaz 4 mg/day and 6% of those taking 8 mg/day.2