New Treatment for Overactive Bladder
Abstract & Commentary
Source: FDA Center for Drug Evaluation and Research. www.fda.gov/cder/approval.
On February 26th, the FDA approved a transdermal formulation of oxybutynin for the treatment of overactive bladder and urinary incontinence. Oxytrol Patch (Watson Pharmaceuticals) provides 3.9 mg/d and can be administered twice per week. The transdermal delivery avoids initial first-pass liver metabolism of the oral oxybutynin formulations and, therefore, significantly less plasma concentration of the active n-desethylooxybutynin metabolite.
With less active metabolite, the sponsoring company has argued that the anticholinergic profile is superior to the oral formulation. The label includes results from 2 phase 3 studies. The first compared the patch to placebo, and the second trial looked at the patch in reference to standard oral therapy. This study was a 12-week, double-blind, double-dummy, placebo-controlled trial with 361 patients, randomized into 3 treatment arms—1 arm received the 3.9 mg/d patch twice weekly, another received 4 mg of Detrol LA daily, and the last received placebo. Subjects were required to have at least 4 urge incontinent episodes and at least 24 voids (of less than 350 cc) as recorded in a 3-day diary during the baseline phase of the study. The primary end point for the study was the change in the number of incontinent episodes. The preliminary results show that Oxytrol and Detrol LA both reduced incontinent episodes by 62% and 64%, respectively, compared to the 42% decline from baseline in the placebo population (P < .001). In terms of side effects, dry mouth from the Detrol LA was 7.4%, which was statistically different from the placebo rate of 1.7% (P < .001). The 4.7% incidence of dry mouth with the Oxytrol Patch was not statistically different. However, the Oxytrol Patch did show an 18% incidence of skin irritation. This was not enough of a problem to warrant discontinuation of the drug. Watson plans to publish the full results in mid-2003.
An alternative transdermal formulation to Ditropan XL and Detrol LA for the treatment of urinary incontinence is a welcome addition to the therapeutic armamentarium. If the improved side effect profile from having less anticholinergic metabolites proves to be a real clinical advantage, the patch may find itself the preferred first-line choice. Regardless, the patch still offers significant benefits considering the special needs of some of our neurologically impaired patients. — Jeffrey Reich
Dr. Reich is Assistant Professor of Neurology, New York Presbyterian Hospital-Cornell Campus.