Development of oxybutynin chloride topical gel for overactive bladder.

Abstract

Overactive bladder (OAB) is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG) is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo-controlled Phase III study.