Clinical Medicine Reviews in Therapeutics

Overactive bladder is a highly prevalent condition that affects both males and females. The risk of developing overactive bladder increases with aging. There appear to be multiple etiologies for overactive bladder. Antimuscarinic agents have been the mainstay for pharmacologic treatment of overactive bladder. Their role is thought to be via antagonism with acetylcholine at the M3 receptor in the detrusor. More recently, the urothelium and suburothelium have been demonstrated to have muscarinic receptors and thus antimuscarinic agents may affect the afferent pathway component of overactive bladder symptoms. Historically, although effective, the use of antimuscarinic agents has been limited by poor tolerability. The development of once daily formulations and alternative methods of delivery, multiple dose agents and agents with variable muscarinic receptor affinity profiles has resulted in improved tolerability profiles while maintaining efficacy. Although effective, antimuscarinic agents typically improve OAB symptoms and are less likely to lead to complete resolution of symptoms. The success rates of antimuscarinic therapy are improved when used in combination with behavioral therapy. Fesoterodine is one of the most recent OAB agents to be approved by the FDA. It acts as a prodrug and is rapidly and extensively metabolized to 5-hydroxymethyltolterodine, which is also the active metabolite of tolterodine. Fesoterodine is available in two formulations and clinical studies have demonstrated a dose-related response in efficacy with fesoterodine. Fesoterodine is well tolerated, the most common side effects being those of dry mouth and constipation. There were very few discontinuations in the clinical trials due to either dry mouth or constipation. Fesoterodine’s long-term efficacy and tolerability has been demonstrated in the 3-year open label extension trial with fesoterodine. A thorough QT study confirmed the absence of an effect on the QT interval with standard dosing of fesoterodine, 4 mg or a high dose, 28 mg of fesoterodine. Due to multiple metabolic pathways, via the CYP P450 system and excretion by the kidneys, there are limited dosing restrictions with fesoterodine. Fesoterodine is the only antimuscarinic therapy available that comes with the YOURWAY plan, a multidimensional program that brings together pharmacotherapy with education and skills training.