Darifenacin: Another Antimuscarinic for Overactive Bladder

Guay, D.R.P.

The Consultant Pharmacist 20(5): 424-431


DOI: 10.4140/tcp.n.2005.424
Accession: 068492573

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To review darifenacin, a new anticholinergic for overactive bladder, approved in December 2004 by the U.S. Food and Drug Administration. A MEDLINE/PUBMED search was conducted to identify pertinent studies in the English language. In addition, proceedings of meetings of the International Continence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts. Additional references were obtained from the bibliographies of these sources. Data over the time period of 1986 through September 2004 were reviewed. All studies evaluating any aspect of darifenacin in vitro or in vivo in animals or humans. Preclinical studies demonstrated that darifenacin was an antagonist at muscarinic cholinergic M1, M3, and M5 receptors. On the basis of preclinical data, darifenacin was felt to be a "uroselective" antimuscarinic. Darifenacin is extensively metabolized, with urinary excretion of parent compound being less than 10%. Darifenacin, dosed as 7.5 or 15 mg once daily, is significantly superior to placebo in reducing the numbers of micturitions, urges, incontinence episodes, and urge severity and increasing the warning time and volume per micturition. No active-controlled trial data are available. The most problematic adverse effects of darifenacin are the anticholinergic effects of dry mouth and constipation. Although promising in preclinical studies, the "uroselectivity" of the anticholinergic activity of darifenacin has not been confirmed in clinical trials. No comparative data with marketed (for overactive bladder) anticholinergics are available. On the basis of available data, darifenacin does not appear to be a substantial advance upon existing anticholinergics in the management of overactive bladder.