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Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX® in the Treatment of Overactive Bladder
ENABLEX® is a registered trademark of Warner Chilcott Company, LLC.
ENABLEX® (darifenacin) extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 2
Presenter
David C. Chaikin, MD, FACSClinical Assistant Professor of Urology
New York-Presbyterian/Weill Cornell Medical CenterNew York, New York
Attending UrologistMorristown Memorial Hospital
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 3
Table of Contents
Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Overactive BladderBackground: Disease State and Epidemiology
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Coyne KS, et al. Urology. 2011; 77:1081-1087.
Overactive Bladder Is a Complex Syndrome
5
Urgency 12.6%
Urge Urinary Incontinence
9.1%
Urgency + Frequency
5.2%1.2%
Urgency + Urge Urinary Incontinence
13.1%
Urgency + Urge Urinary
Incontinence + Frequency
7.0%
Prevalence of Overactive Bladder Symptoms in Poll of 2000 Adults Aged ≥40 Years
Urge Urinary Incontinence +
Frequency
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Overactive Bladder Affects Over 33 Million Americans
According to the National Overactive Bladder Evaluation (NOBLE) Program
Kelleher CJ. Eur Urol Suppl. 2002;1:11-16.
*Overactive bladder dry: ≥4 episodes of urgency during the preceding 4 weeks and either frequency of >8 voids per day or the use of ≥1 coping behaviors to control bladder function.
†Overactive bladder wet: same criteria as overactive bladder dry, plus ≥3 episodes of urinary incontinence in the past 4 weeks that could not be explained by stress symptoms.
6
21.2 million (10.5% of the US adult population)
12.2 million (6.1% of the US
adult population)
Incontinent(overactive bladder wet†)
Continent(overactive bladder dry*)
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 7
Overactive Bladder Risk Factors
*Include elevated body mass index (BMI) and diabetes.
1.Stewart WF, et al. World J Urol. 2003;20:327-336.2.Teleman PM, et al. BJOG. 2004;111:600-604.3.Rosenberg MT, et al. Cleve Clin J Med. 2007;74(suppl 3):S21-S29.4.Thüroff JW, et al. Eur Urol. 2011;59:387-400.
Increased Age1
Abnormal Metabolic Factors2*
Medications3
Pregnancy and Vaginal
Delivery (Women)4
Prostate-related
Conditions (Men)3,4
Pelvic Surgery3
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 8
Comorbidities Associated With Overactive Bladder
Falls and Fractures
DepressionSleep
Disturbances
Urinary Tract and Skin
Infections
Brown JS, et al. Am J Manag Care. 2000;6(suppl 11):S574-S579.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Overactive Bladder Negatively Affects QOL
*A standardized questionnaire that measures health-related QOL.
Modified from Stewart WF, et al. World J Urol. 2003;20:327-336.
Dec
reas
e in
M
ean
SF-3
6 Sc
ore
(%)
Patients With Overactive Bladder Urge Incontinence Compared With Controls (SF-36)*
9
QOL Areas of Measure
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Options: Pharmacologic andNon-Pharmacologic Therapies
Non-Pharmacologic (Behavioral Therapy)2
Lifestyle management•Limiting excessive water or caffeine intake
Bladder training•Increasing bladder capacity through lengthening of the voiding interval
Physical therapy•Pelvic floor exercises•Biofeedback therapy
Toileting assistance•Timed and patterned toileting guidance
1. Thüroff JW, et al. Eur Urol. 2011;59:387-400.2. Yamaguchi O, et al. Int J Urol. 2009;16:126-142.
Pharmacologic Therapy1*
• Antimuscarinic drugs
• Drugs acting on membrane channels
• Antidepressants
• Alpha-adrenoreceptor antagonists
• Beta-adrenoreceptor antagonists
• Phosphodiesterase type-5 inhibitors (in men)
• Cyclo-oxygenase (COX) inhibitors
• Hormones
*Recommendations for pharmacologic therapy are from the European Association of Urology (EAU) guidelines for incontinence.
10
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 11
M3 Receptor Selectivity Allows for Targeting of Tissue of Intent
Abrams P, et al. Br J Pharmacol. 2006;148:565-578.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 12
Targets for Muscarinic Receptor Inhibition
1. Abrams P, et al. Br J Pharmacol. 2006;148:565-578.2. Sarria B, et al. Am J Physiol Lung Cell Mol Physiol. 2002;283:L1125-L1132.
Cerebral cortexHippocampusEyesSalivary glands
Cardiac muscleEyesSmooth muscle (bronchus)HippocampusHind brain
Impacts:Memory, cognitive function,saliva, tear secretion
Impacts:Heart rate,tear secretion,bronchodilation
Smooth muscle (bladder, bowel)
Salivary glandsEyesBrain
Impacts:Bladder contraction,*bowel motility, saliva,tear secretion,visual accommodation
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 13
M3-specific Targeted Therapy for Overactive Bladder• High affinity for the M3 receptor1-3
– Targets the smooth muscle to minimize leaks and accidents1
– Minimizes potential CNS- and CV-related side effects2,3
• M3-selective antagonists do not significantly affect memory3 – Compared with placebo– Significant memory deterioration has been demonstrated
with less-selective agents, such as oxybutynin
1. Abrams P, et al. Br J Pharmacol. 2006;148:565-578.2. Lipton RB, et al. J Urol. 2005;173:493-498.3. Kay G, et al. Eur Urol. 2006;50:317-326.
CNS=central nervous system; CV=cardiovascular.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 14
ENABLEX®: Muscarinic Receptor Selectivity
• M3 receptors are the primary mediators of detrusor contractility in the bladder1
• M3 receptors are also involved in gastrointestinal smooth-muscle contraction, saliva production, and iris sphincter function1,2
14
NA=not available.1. Abrams P, et al. Br J Pharmacol. 2006;148:565-578.2. ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.3. Geriatric Consultant Resources LLC. http://www.gcrweb.com/OABdss/comprehensive/comp-02a-muscar.htm. Accessed March 25, 2011.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 15
Likelihood of Muscarinic Agents Crossing the BBB
1. Lipton RB, et al. J Urol. 2005;173:493-498.2. Kay G, et al. Clin Ther. 2005;27:127-138.3. VESIcare® [package insert]. Deerfield, IL: Astellas Pharma US, Inc; 2011.4. Geriatric Consultant Resources, LLC. http://www.gcrweb.com/OABdss/comprehensive/comp-02b-pham.htm. Accessed March 23, 2011.
• Less-selective agents have been associated with more impairment of cognitive function1
BBB= blood-brain barrier. *kDa=kiloDalton.
Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX® as a Treatment Option for Patients With Overactive BladderProven Efficacy and Safety by Clinical Trials
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 17
ENABLEX®:Prescribing Information
• ENABLEX® (darifenacin) extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
Indication and Usage
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 18
ENABLEX®:Prescribing Information
• ENABLEX® (darifenacin) extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
• ENABLEX® (darifenacin) extended-release tablets are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma and in patients who are at risk for these conditions. ENABLEX® is also contraindicated in patients with known hypersensitivity to the drug or any of its ingredients
Indication and Usage
Contraindications
ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 19
ENABLEX®:Prescribing Information
• ENABLEX® (darifenacin) extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
• ENABLEX® (darifenacin) extended-release tablets are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma and in patients who are at risk for these conditions. ENABLEX® is also contraindicated in patients with known hypersensitivity to the drug or any of its ingredients
Indication and Usage
Contraindications
ENABLEX® should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention; gastrointestinal obstructive disorders because of the risk of gastric retention; severe constipation, ulcerative colitis, or myasthenia gravis. In patients being treated for narrow-angle glaucoma, ENABLEX® should be used with caution and only where the potential benefits outweigh the risks.
Angioedema of the face, lips, tongue, and/or larynx have been reported with darifenacin, in some cases, after the first dose. Angioedema associated with upper airway swelling may be life threatening. Patients should be advised to promptly discontinue darifenacin therapy and seek immediate medical attention if they experience edema of the tongue or laryngopharynx, or difficulty breathing.
ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 20
• ENABLEX® has been evaluated in 3 randomized, fixed-dose, placebo-controlled, multicenter, double-blind, 12-week studies and 1 randomized, double-blind, placebo-controlled, multicenter, dose-titration study
• In clinical studies, dry mouth and constipation were the most commonly reported adverse events (AEs)
ENABLEX®:Prescribing Information
ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 21
ENABLEX®: Effective Treatment for Overactive Bladder
1. ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.2. Serra DB, et al. J Clin Pharmacol. 2005;45:1038-1047.3. Haab F, et al. BJU Int. 2006;98:1025-1032.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 2222
Chapple C, et al. BJU Int. 2005;95:993-1001.
ENABLEX® Pooled Analysis of Phase 3 Studies
0 2 6 12
ENABLEX® 7.5 mg Once Daily (n=337)
Placebo Once Daily (n=388)
Up to 4 weeks(as needed)
Study Visits (weeks)
Washout Treatments
ENABLEXENABLEX®® 15 mg Once Daily (n=334) 15 mg Once Daily (n=334)
Rand
omiz
ation
Primary Efficacy Change in number of incontinence episodes per week
Secondary Efficacy Number of significant leaks per week
Voiding frequency
Bladder capacity
Frequency and severity of urgency
Number of nocturnal awakenings caused by overactive bladder
Subject population similar between treatment arms
Symptoms of overactive bladder
≥6 months
3 Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Fixed-dose, 12-week Studies
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 23
7.5 mg ENABLEX® Significantly Reduces Incontinence Episodes by ~70%
23
Chapple C, et al. BJU Int. 2005;95:993-1001.*P=.004 vs placebo; data missing for 2 subjects.
Treatment
Darifenacin 7.5 mg* Placebo
Data from a pooled analysis of 3 phase 3, fixed-dose, double-blind, placebo-controlled, parallel-group, 12-week clinical trials (1001, 1002, 1041). A total of 1059 subjects were included in the analysis (darifenacin 7.5 mg: n=337; darifenacin 15 mg: n=334; placebo: n=388). Absolute changes from baseline (last observation carried forward [LOCF]) to Week 12 for subjects on darifenacin: number of weekly incontinence episodes: –8.8 (7.5 mg) and –10.6 (15 mg).
n=335 n=271
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 24
15 mg ENABLEX® Significantly Reduces Incontinence Episodes by >75%
24
Chapple C, et al. BJU Int. 2005;95:993-1001.
*P<.001 vs placebo; data missing for 4 subjects.
Treatment
Darifenacin 15 mg* Placebo
Data from a pooled analysis of 3 phase 3, fixed-dose,double-blind, placebo-controlled, parallel-group, 12-week clinical trials (1001, 1002, 1041). A total of 1059 subjects were included in the analysis (darifenacin 7.5 mg: n=337; darifenacin 15 mg: n=334; placebo: n=388). Absolute changes from baseline (last observation carried forward [LOCF]) to Week 12 for subjects on darifenacin: number of weekly incontinence episodes: –8.8 (7.5 mg) and –10.6 (15 mg).
n=330 n=384
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 25
7.5 mg ENABLEX® Significantly Reduces the Number of Urgency Episodes
25
Chapple C, et al. BJU Int. 2005;95:993-1001.
*P<.005 compared with corresponding placebo.
37%
24%
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 26
15 mg ENABLEX® Significantly Reduces the Number of Urgency Episodes
26
Chapple C, et al. BJU Int. 2005;95:993-1001.
39%
23%
*P<.01 compared with corresponding placebo.
*
49%
34%
*
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 27
ENABLEX® Is Well-tolerated
27
UTI=urinary tract infection.1. ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.2. Chapple C, et al. BJU Int. 2005;95:993-1001.
Treatment-emergent AEs (TEAEs) Over 1 Year1,2
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Few Discontinuations Over 12 Weeks
28
Chapple C, et al. BJU Int. 2005;95:993-1001.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX® Long-term Efficacy Up to 2 Years
Haab F, et al. BJU Int. 2006;98:1025-1032.
ENABLEXENABLEX® 7.5 mg Once Daily 7.5 mg Once Daily
12-week Studies Long-term Study (24 months)
ENABLEXENABLEX® 15 mg Once Daily 15 mg Once Daily
ENAB
LEX®
7.5
m
g
for
2
Wee
ks
Study 1 (n=526)ENABLEX® 3.75, 7.5, 15 mg, and Placebo
Study 2 (n=357)ENABLEXENABLEX®® 7.5, 15 mg, and Placebo
Multicenter, Long-term, Noncomparative, Open-label Study
Subjects recruited from 1 of 2 phase 3, randomized, double-blind, 12-week studies
Primary Objective
Assess long-term safety and tolerability
Secondary Objective
Evaluate long-term efficacy
29
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX® Significantly Reduces Incontinence Episodes Up to 2 Years
Treatment Duration (months)1. Haab F, et al. BJU Int. 2006;98:1025-1032.2. Hill S, et al. Curr Med Res Opin. 2007;23:2697-2704.
Results from an open-label, nonrandomized, multicenter, 2-year extension study. Subjects were enrolled from two 12-week, phase 3, double-blind,
placebo-controlled pivotal trials1,2
30
P<.001 vs pivotal study baseline
n=667 n=598 n=541 n=495 n=464
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Low Discontinuation Rates Through 2 Years
31
1. Haab F, et al. BJU Int. 2006;98:1025-1032.2. Haab F, et al. Eur Urol. 2004;45:420-429.3. Steers W, et al. BJU Int. 2005;95:580-586.
Most commonly reported TEAEs were similar to pivotal studies and included dry mouth, constipation, dyspepsia, and headache1-3
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 32
PPBC=Patient Perception of Bladder Condition.Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674.
Primary Efficacy
Change in PPBC score from baseline to end of study
Secondary Efficacy
Micturition frequency
Urgency
Urge urinary incontinence episodes after 2, 6, and 12 weeks of treatment compared with baseline
• Subjects were ENABLEX®-naïve and reported lack of sufficient effect and/or AEs on previous treatments with either oxybutynin or tolterodine
ENABLEXENABLEX® 7.5 mg Once Daily (n=180) 7.5 mg Once Daily (n=180)
2-3 weeks
Screening/WashoutTreatments
(optional dose escalation after 2 weeks)
ENABLEXENABLEX® 15 mg Once Daily (n=302) 15 mg Once Daily (n=302)
Baseline1 week 10 weeks
ENABLEX® 7.5 mg Once Daily
(n=497)Enrollment (n=500)
2 weeks
12-Week, Open-label, Single-arm, Multicenter Study
Efficacy in Subjects on Previous Overactive Bladder Therapy
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX® Significantly* Improves Patient -reported Bladder Control
33
Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674.
Results of PPBC
p <0.0001.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX®: Cognitive Function in Older Subjects
Kay G, et al. Eur Urol. 2006;50:317-326.
0 1 2 3
Cognitive Function
Tests (weeks)
Washout Treatments
Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, 3-week Study
Primary Efficacy
Effect on recent (delayed) memory using Name-Face Association Test at Week 3
Secondary Efficacy
Recall on First-Last Name Association Test
Misplaced Objects Test
Delayed recall scores at weeks 1 and 2
Effects on immediate memory
Visual attention
Information processing
Psychomotor/reaction time
34
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX®: Memory Sparing
*P<.05 vs placebo;†P<.05 vs ENABLEX® (ANCOVA, adjusted for baseline score, age, and gender).ANCOVA=analysis of covariance.
Kay G, et al. Eur Urol. 2006;50:317-326.
• No significant effects on memory
®
* †
35
* †
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 36
ENABLEX®:Effect on QT Interval
QTcF=Fridericia-corrected QT interval.
Serra DB, et al. J Clin Pharmacol. 2005;45:1038-1047.
ENABLEXENABLEX® 15 mg Once Daily (n=47) 15 mg Once Daily (n=47)
Moxifloxacin 400 mg Once Daily (n=48)Moxifloxacin 400 mg Once Daily (n=48)
Treatment Period (Days 1-6)
ENABLEXENABLEX® 75 mg Once Daily (n=46) 75 mg Once Daily (n=46)
Plac
ebo
Run-
in (D
ay –
1)
Placebo (n=47)Placebo (n=47)
7-Day, Single-center, Randomized, Parallel-group Study in Healthy Subjects
Primary Efficacy
Change from mean baseline in QTcF at Tmax
Secondary Efficacy
Mean change from baseline in QT/QTcF
Maximum QT interval postdose change from baseline
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 37
ENABLEX®:Minimal Effect on QT Interval
• No significant changes occurred when ENABLEX® was given at 75 mg (10 times the starting dose)
Serra DB, et al. J Clin Pharmacol. 2005;45:1038-1047.
Change From Baseline in Mean QTcF at Tmax (ms)
Placebo (n=44) –2.6
ENABLEX® 15 mg (n=46) –2.6
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 38
Efficacy
• Significant reduction in number of incontinence and urgency episodes per week1
• Overactive bladder symptoms significantly improved in subjects who were dissatisfied with prior antimuscarinic therapy2
Specificity
• Strong affinity for M3 receptors3
• No significant effects on delayed or immediate recall memory in older subjects4
• No significant change in QTcF5
Well Studied
• 2-year extension study demonstrated a favorable safety, tolerability, and efficacy profile6,7
• In subjects ≥65 years of age, ENABLEX® was well tolerated; no overall differences in safety or efficacy were observed3,7
1. Chapple C, et al. BJU Int. 2005;95:993-1001.2. Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674.3. ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.4. Kay G, et al. Eur Urol. 2006;50:317-326.5. Serra DB, et al. J Clin Pharmacol. 2005;45:1038-1047.6. Haab F, et al. BJU Int. 2006;98:1025-1032.7. Hill S, et al. Curr Med Res Opin. 2007;23:2697-2704.
ENABLEX® Clinical Trial Data: Established Efficacy and Safety
Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX®
as a Treatment Option for Patients With Overactive BladderCase Studies
Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Amy S.• 52-year-old woman with overactive bladder• Active lifestyle• Overactive bladder treatment-naive
40
Case Study 1
Case studies are illustrative examples and not based on actual patient records.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Amy S.
• 52-year-old, teacher, mother of 4
• Active lifestyle (skis, golfs)
• Tried Kegel exercises
• No other significant medical history
• Meds: statin, NSAIDs
• CC: Strong urge to urinate during the day
• Every 30 minutes
Medical History
41
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Amy S. (cont’d)
• No incontinence with coughing, sneezing, laughing, or exercise
unless bladder is full
• Overactive bladder increasingly difficult to control
• Accidents have hindered activities
• No history of previous overactive bladder medication use
• Embarrassed by her overactive bladder symptoms
• Desires a safe and effective treatment
Medical History
42
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Assessment
43
Amy S. is a 52-year-old woman with an active lifestyle
•Based on history and symptoms, you agree with the diagnosis of overactive bladder
•You perform a physical exam and order routine tests to rule out other causes
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
44
After considering Amy’s medical history, how would you manage her overactive bladder?
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 45
Chapple C, et al. BJU Int. 2005;95:993-1001.
After considering Amy’s medical history, how would you manage her overactive bladder?
ENABLEX® as an OptionIn clinical studies, ENABLEX® has demonstrated significant reductions in incontinence and urgency episodes
Treatment Plan
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 46
After considering Amy’s medical history, how would you manage her overactive bladder?
ENABLEX® as an OptionIn clinical studies, ENABLEX® has demonstrated significant reductions in incontinence and urgency episodes1
Discontinuation rates from 3 phase 3 studies were minimal1,2
Treatment Plan
1. Chapple C, et al. BJU Int. 2005;95:993-1001.2. Serra DB, et al. J Clin Pharmacol. 2005;45:1038-1047.
Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 47
Case Study 2George R.• 69-year-old man•Dissatisfied with current overactive bladder therapy •Considering changing medication for overactive bladder
Case studies are illustrative examples and not based on actual patient records.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
George R.
• 69-year-old retired businessman
• Overactive bladder diagnosed
6 years ago
• Reluctant to change overactive
bladder medication because the first
one failed
• CC: Despite treatment, patient
complains of strong and frequent
urges to void
48
Medical History
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
George R. (cont’d)
• Medications • ACE inhibitor
• Oral hypoglycemic
• Concerned that switching treatments may
have potential side effects and not provide
further symptom relief
• Seeks an alternative treatment that is safe,
effective, and can be used longterm
49
Medical History
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Assessment
50
George R. is a 69-year-old man requesting treatment for his symptoms
•Based on history and symptoms, you agree with the diagnosis of overactive bladder
•Perform a physical exam , including prostate exam, and order routine tests, to rule out other causes
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
51
After considering George’s medical history and chief complaint of strong and frequent urges to urinate, how would you manage his overactive bladder?
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
52
After considering George’s medical history and chief complaint of strong and frequent urges to urinate, how would you manage his overactive bladder?
ENABLEX® as an OptionAntimuscarinics are currently the treatment of choice in elderly patients with overactive bladder1
1. Chughtai B, et al. Clin Interv Aging. 2008;3:503-509.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
53
After considering George’s medical history and chief complaint of strong and frequent urges to urinate, how would you manage his overactive bladder?
ENABLEX® as an OptionAntimuscarinics are currently the treatment of choice in elderly patients with overactive bladder1
Significant improvements in PPBC scores at week 12 in patients switching from other overactive bladder treatments2
1. Chughtai B, et al. Clin Interv Aging. 2008;3:503-509. 2. Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
54
After considering George’s medical history and chief complaint of strong and frequent urges to urinate, how would you manage his overactive bladder?
ENABLEX® as an OptionAntimuscarinics are currently the treatment of choice in elderly patients with overactive bladder1
Significant improvements in PPBC scores at week 12 in patients switching from other overactive bladder treatments2
High M3 specificity with no significant effect on memory3,4
1. Chughtai B, et al. Clin Interv Aging. 2008;3:503-509. 2. Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674. 3. Lipton RB, et al. J Urol. 2005;173:493-498. 4. Kay G, et al. Eur Urol. 2006;50:317-326.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
55
After considering George’s medical history and chief complaint of strong and frequent urges to urinate, how would you manage his overactive bladder?
ENABLEX® as an OptionAntimuscarinics are currently the treatment of choice in elderly patients with overactive bladder1
Significant improvements in PPBC scores at week 12 in patients switching from other overactive bladder treatments2
High M3 specificity with no significant effect on memory3,4
Consistent efficacy and safety in 12-week pivotal studies and a 2-year extension study5-7
1. Chughtai_B, et al. Clin Interventions Aging. 2008; 3:503-509. 2. Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674. 3. Lipton RB, et al. J Urol. 2005;173:493-498. 4. Kay G, et al. Eur Urol. 2006;50:317-326. 5. Haab F, et al. BJU Int. 2006;98:1025-1032. 6. Hill S, et al. Curr Med Res Opin. 2007;23:2697-2704. 7. Steers W, et al. BJU Int. 2005;95:580-586.
Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 56
Case Study 3Joanne J.• 78-year-old woman•Worried about side effects of overactive bladder treatment• History of memory loss
Case studies are illustrative examples and not based on actual patient records.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 57
Joanne J.
• 78-year-old retired waitress with dementia
• Lives with daughter
• Overactive bladder for >15 years
• CC: Incontinence limiting her activity
• Concerned that overactive bladder
medications can further compromise her
memory
Medical History
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 58
Joanne J. (cont’d)
• Medications: • ACE inhibitor• Cardioselective beta blocker
• Antihyperlipidemic
• Wants to decrease her frequent accidents
and subsequent burden on family
Medical History
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Assessment
59
Joanne J. is a 78-year-old woman with history of memory loss who presents with her caretaker (daughter) requesting alternative treatment for her overactive bladder symptoms
•Based on history and symptoms, you agree with the diagnosis of overactive bladder
•You perform a physical exam and order routine tests, including a urine analysis, to rule out other causes
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
60
After reviewing Joanne’s history and treatment concerns, how would you manage her overactive bladder?
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
61
After reviewing Joanne’s history and treatment concerns, how would you manage her overactive bladder?
ENABLEX® as an OptionAs bladder contractions are mediated primarily by
M3 receptors, antimuscarinics with high M3 specificity are ideal for patients with overactive bladder 1
1. Chapple C, et al. BJU Int. 2005;95:993-1001.
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Treatment Plan
62
After reviewing Joanne’s history and treatment concerns, how would you manage her overactive bladder?
ENABLEX® as an OptionAs bladder contractions are mediated primarily by
M3 receptors, antimuscarinics with high M3 specificity are ideal for patients with overactive bladder1
This is particularly important in elderly patients, who are more vulnerable to potential CNS and other safety concerns2,3
1. Chapple C, et al. BJU Int. 2005;95:993-1001. 2. Kay G, et al. Eur Urol. 2006;50:317-326. 3. Serra DB, et al. J Clin Pharmacol. 2005;45:1038-1047.
Please see Selected Safety Information for ENABLEX® on slide 62, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
Please see Selected Safety Information for ENABLEX® on slide 66 and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING
ENABLEX® Treatment in a Wide Range of Patients With Overactive Bladder
Summary
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 64
1. Chapple C, et al. BJU Int. 2005;95:993-1001. 2. Zinner N, et al. Int J Clin Pract. 2008;62:1664-1674. 3. ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011. 4. Kay G, et al. Eur Urol. 2006;50:317-326. 5. Serra DB, et al. J Clin Pharmacol. 2005;45:1038-1047. 6. Haab F, et al. BJU Int. 2006;98:1025-1032. 7. Hill S, et al. Curr Med Res Opin. 2007;23:2697-2704.
ENABLEX®:Effective Treatment for Overactive Bladder Patients
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 65
ENABLEX®:Overactive Bladder Treatment for a Wide Range of Patients
First-line therapy for the active 52-year-old woman• Significant reductions in incontinence and urgency episodes• Minimal discontinuation rates
Treatment for the 69-year-old man who was dissatisfied with previous therapy• Significant improvements in PPBC in patients switching from other overactive
bladder therapies• Consistent efficacy and safety in 12-week pivotal studies and a 2-year
extension study
Therapy for the 78-year-old woman with safety concerns • High M3 selectivity• Low risk of memory deterioration and other AEs
Who is your patient?• •
65
Please see Selected Safety Information for ENABLEX® on slide 66, and Full Prescribing Information, which includes the Patient Information, provided by your sales representative and at www.enablex.com.PROPRIETARY AND CONFIDENTIAL - NOT TO BE COPIED, DISTRIBUTED, OR USED IN DETAILING 66
ENABLEX®:Important Safety Information
ENABLEX® (darifenacin) extended-release tablets is contraindicated in patients with urinary retention, gastric retention or uncontrolled narrow-angle glaucoma, and in patients who are at risk for these conditions. ENABLEX® is also contraindicated in patients with known hypersensitivity to the drug or any of its ingredients.
Daily dose should not exceed 7.5 mg when used with potent CYP3A4 inhibitors or in patients with moderate hepatic impairment. ENABLEX® is not recommended for patients with severe hepatic impairment.
ENABLEX® should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention; gastrointestinal obstructive disorders because of the risk of gastric retention; severe constipation, ulcerative colitis, or myasthenia gravis. In patients being treated for narrow-angle glaucoma, ENABLEX® should be used with caution and only where the potential benefits outweigh the risks.
Angioedema of the face, lips, tongue, and/or larynx have been reported with darifenacin, in some cases after the first dose. Angioedema associated with upper airway swelling may be life threatening. Patients should be advised to promptly discontinue darifenacin therapy and seek immediate medical attention if they experience edema of the tongue or laryngopharynx, or difficulty breathing.
In controlled clinical studies the incidence of the most frequently reported adverse events for ENABLEX® 7.5 mg or 15 mg and greater than placebo was: dry mouth (20.2%, 35.3%, 8.2%); constipation (14.8%, 21.3%, 6.2%); dyspepsia (2.7%, 8.4%, 2.6%); abdominal pain (2.4%, 3.9%, 0.5%); nausea (2.7%, 1.5%, 1.5%); diarrhea (2.1%, 0.9%, 1.8%); urinary tract infection (4.7%, 4.5%, 2.6%); dizziness (0.9%, 2.1%, 1.3%); asthenia (1.5%, 2.7%, 1.3%); and dry eyes (1.5%, 2.1%, 0.5%).
Please see full Prescribing Information for ENABLEX® at www.enablex.com.
ENABLEX® [package insert]. Rockaway, NJ: Warner Chilcott (US), LLC; 2011.