RxPRODUCT NEWS: PROFILE: Enablex (darifenacin)

Urinary incontinence is a significantproblem affectingapproximately 17% of thepopulation in the United States andEurope.¹ It does not have a single exactcause but rather several contributingfactors, particularly age, urinary tractinfections, estrogen deficiency, andprostate enlargement.² Urinary incontinenceaffects health care costs, morbidityrates, and quality of life issues,including embarrassment and interferingwith daily activities.² Enablex, marketedby Novartis, is indicated for thetreatment of overactive bladder withsymptoms of urge urinary incontinence,urgency, and frequency.³

Pharmacology

Enablex is a muscarinic receptorantagonist with a superior affinity forM3 receptors. Muscarinic receptors,specifically M3 receptors, are responsiblefor contraction of the humanbladder muscle and gastrointestinalsmooth muscle, saliva production,and iris sphincter function. By blockingM3 receptors, Enablex helps reduceincontinence episodes, decrease urinationfrequency, and reduce the urgencyassociated with urination.^3,4

Clinical Trials

A double-blind, randomized, placebo-controlled study examined theeffects of once-daily oral Enablex (3.75,7.5, or 15 mg), compared with matchingplacebo, in 561 patients havingoveractive bladder symptoms for morethan 6 months. At the end of 12 weeks,the results showed that doses of 7.5and 15 mg had produced a significant,sustained improvement. The numberof incontinence episodes per week wasreduced from baseline by 67.7% with7.5 mg of Enablex and by 72.8% with15 mg, compared with 55.9% withplacebo (P = .010 and P = .017, respectively).The investigators concludedthat Enablex significantly improves themajor symptoms of overactive bladderwith no significant central nervous system(CNS) or cardiac adverse events.⁵

Another multicenter, double-blind,12-week study utilized a flexibleEnablex dosing strategy. Patients wererandomized to receive once-dailyEnablex 7.5 mg (n = 268) or matchingplacebo (n = 127) for the first 2 weeks.The dose was increased to once-dailyEnablex 15 mg or placebo if additionalefficacy was necessary. At 12 weeks, theEnablex group showed a 63.1% reductionin the number of incontinenceepisodes, compared with a 48.1%reduction in the placebo group (P =.035). The Enablex group also exhibitedsignificant benefits in voiding frequency,bladder capacity, frequency ofurgency, severity of urgency, and numberof significant leaks, compared withthe placebo group.⁶

Safety

Enablex generally is well tolerated,by patients >65 years of age as well asby others. Dry mouth and constipationwere the 2 most commonlyreported adverse events.^3,4 Cardiovasculartolerability and CNS profiles ofEnablex were similar to those of theplacebo. In the event of an overdose,however, electrocardiograph monitoringis highly recommended. Enablex isin pregnancy category C and shouldbe utilized in pregnancy only if thebenefit to the mother outweighs thepossible risk to the fetus.³Enablex is contraindicated in

patients who are at risk or currentlysuffer from urinary retention, gastricretention, or uncontrolled narrowangleglaucoma.^3,4 The coadministrationof CYP3A4 potent inhibitors—such as ketoconazole, itraconazole,ritonavir, clarithromycin, and nefazodone—can increase the bioavailabilityof Enablex by approximately 100%.The daily dose of Enablex in thesepatients should not exceed 7.5 mg.³

No dosage adjustment is needed inpatients with renal impairment. Inpatients with moderate hepatic impairment,however, it is recommended notto exceed a daily dose of 7.5 mg.^3,4

Outlook

Enablex is available in 7.5-and15-mg extended-release tablets andcan be stored at room temperature.The recommended starting dose ofEnablex is 7.5 mg orally once daily.After 2 weeks of treatment, the dosemay be increased to 15 mg orally oncedaily. The tablets can be taken withoutregard to food but should be swallowedwhole with liquid.³ Overall,Enablex offers a safe and effective therapeuticprofile with an uncomplicateddosing regimen. These attractive featuresgive health care practitionersanother excellent option for the treatmentof overactive bladder.

Drs. Faria and Soo are both senior researchpharmacists with the Investigational DrugService at Brigham and Women's Hospital,Boston, Mass. Dr. Faria also is a seniorhuman research specialist at PartnersHealthCare System. Ms. Keller is a sixth-yearPharmD Candidate from the MassachusettsCollege of Pharmacy, currently on clinicalclerkship in the Investigational Drug Service atBrigham & Women's Hospital.

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