RxPRODUCT NEWS: PROFILE: Enablex (darifenacin)

Author: Claudio Faria, PharmD, RPh; Carolyn Soo, PharmD, RPh; and Stephanie Keller

Urinary incontinence is a significant problem affecting approximately 17% of the population in the United States and Europe.1 It does not have a single exact cause but rather several contributing factors, particularly age, urinary tract infections, estrogen deficiency, and prostate enlargement.2 Urinary incontinence affects health care costs, morbidity rates, and quality of life issues, including embarrassment and interfering with daily activities.2 Enablex, marketed by Novartis, is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.3

Pharmacology

Enablex is a muscarinic receptor antagonist with a superior affinity for M3 receptors. Muscarinic receptors, specifically M3 receptors, are responsible for contraction of the human bladder muscle and gastrointestinal smooth muscle, saliva production, and iris sphincter function. By blocking M3 receptors, Enablex helps reduce incontinence episodes, decrease urination frequency, and reduce the urgency associated with urination.3,4

Clinical Trials

A double-blind, randomized, placebo- controlled study examined the effects of once-daily oral Enablex (3.75, 7.5, or 15 mg), compared with matching placebo, in 561 patients having overactive bladder symptoms for more than 6 months. At the end of 12 weeks, the results showed that doses of 7.5 and 15 mg had produced a significant, sustained improvement. The number of incontinence episodes per week was reduced from baseline by 67.7% with 7.5 mg of Enablex and by 72.8% with 15 mg, compared with 55.9% with placebo (P = .010 and P = .017, respectively). The investigators concluded that Enablex significantly improves the major symptoms of overactive bladder with no significant central nervous system (CNS) or cardiac adverse events.5

Another multicenter, double-blind, 12-week study utilized a flexible Enablex dosing strategy. Patients were randomized to receive once-daily Enablex 7.5 mg (n = 268) or matching placebo (n = 127) for the first 2 weeks. The dose was increased to once-daily Enablex 15 mg or placebo if additional efficacy was necessary. At 12 weeks, the Enablex group showed a 63.1% reduction in the number of incontinence episodes, compared with a 48.1% reduction in the placebo group (P = .035). The Enablex group also exhibited significant benefits in voiding frequency, bladder capacity, frequency of urgency, severity of urgency, and number of significant leaks, compared with the placebo group.6

Safety

Enablex generally is well tolerated, by patients >65 years of age as well as by others. Dry mouth and constipation were the 2 most commonly reported adverse events.3,4 Cardiovascular tolerability and CNS profiles of Enablex were similar to those of the placebo. In the event of an overdose, however, electrocardiograph monitoring is highly recommended. Enablex is in pregnancy category C and should be utilized in pregnancy only if the benefit to the mother outweighs the possible risk to the fetus.3 Enablex is contraindicated in

patients who are at risk or currently suffer from urinary retention, gastric retention, or uncontrolled narrowangle glaucoma.3,4 The coadministration of CYP3A4 potent inhibitors—such as ketoconazole, itraconazole, ritonavir, clarithromycin, and nefazodone—can increase the bioavailability of Enablex by approximately 100%. The daily dose of Enablex in these patients should not exceed 7.5 mg.3

No dosage adjustment is needed in patients with renal impairment. In patients with moderate hepatic impairment, however, it is recommended not to exceed a daily dose of 7.5 mg.3,4

Outlook

Enablex is available in 7.5-and 15-mg extended-release tablets and can be stored at room temperature. The recommended starting dose of Enablex is 7.5 mg orally once daily. After 2 weeks of treatment, the dose may be increased to 15 mg orally once daily. The tablets can be taken without regard to food but should be swallowed whole with liquid.3 Overall, Enablex offers a safe and effective therapeutic profile with an uncomplicated dosing regimen. These attractive features give health care practitioners another excellent option for the treatment of overactive bladder.

Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist at Partners HealthCare System. Ms. Keller is a sixth-year PharmD Candidate from the Massachusetts College of Pharmacy, currently on clinical clerkship in the Investigational Drug Service at Brigham & Women's Hospital.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.