Enablex (Darifenacin Extended-Release Tablets)
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Enablex (Darifenacin Extended-Release Tablets)

ENABLEX ®
(darifenacin)

DRUG DESCRIPTION

Enablex is an extended-release tablet for oral administration which contains 7.5 mg or 15 mg darifenacin as its hydrobromide salt. The active moiety, darifenacin, is a potent muscarinic receptor antagonist.

Chemically, darifenacin hydrobromide is (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2diphenylacetamide hydrobromide. The empirical formula of darifenacin hydrobromide is C28H30N2O2•HBr. The structural formula is:

ENABLEX® (darifenacin)  Structural Formula Illustration

Darifenacin hydrobromide is a white to almost white, crystalline powder, with a molecular weight of 507.5.

Enablex is a once-a-day extended-release tablet and contains the following inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose, magnesium stearate, polyethylene glycol, talc, titanium dioxide. The 15 mg tablet also contains iron oxide red and iron oxide yellow.

What are the possible side effects of darifenacin (Enablex)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using darifenacin and call your doctor at once if you have any of these serious side effects:

  • hot, dry skin and extreme thirst;
  • severe stomach pain or constipation;
  • pain or burning when you urinate; or
  • urinating less than usual or not at all.

Less serious side effects may include:

  • dry mouth;
  • dry eyes, blurred vision;
  • mild...

Read All Potential Side Effects and See Pictures of Enablex »

What are the precautions when taking darifenacin extended-release tablets (Enablex)?

Before taking darifenacin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: problems emptying your bladder (urinary retention), severe blockage of stomach/intestines (gastric retention), a certain eye condition (uncontrolled narrow angle glaucoma), severe liver disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other bladder problems (e.g., bladder outflow obstruction),...

Read All Potential Precautions of Enablex »

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Enablex (darifenacin) is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.

DOSAGE AND ADMINISTRATION

The recommended starting dose of Enablex is 7.5 mg once daily. Based upon individual response, the dose may be increased to 15 mg once daily, as early as two weeks after starting therapy.

Enablex should be taken once daily with water. Enablex may be taken with or without food, and should be swallowed whole and not chewed, divided or crushed.

For patients with moderate hepatic impairment (Child-Pugh B) or when co-administered with potent CYP3A4 inhibitors (for example, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone), the daily dose of Enablex should not exceed 7.5 mg. Enablex is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, Use in Specific Populations and CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

Enablex extended-release tablets 7.5 mg are round, shallow, bi-convex, white-colored tablets, and are identified with “DF” on one side and “7.5” on the reverse.

Enablex extended-release tablets 15 mg are round, shallow, bi-convex, light peach-colored tablets, and are identified with “DF” on one side and “15” on the reverse.

Storage And Handling

Enablex®,7.5 mg are round, shallow, bi-convex, white-colored tablets, and are identified with “DF” on one side and “7.5” on the reverse.

Bottle of 30..............................NDC 0430-0170-15
Bottle of 90..............................NDC 0430-0170-23

Enablex®, 15 mg are round, shallow, bi-convex, light peach-colored tablets, and are identified with “DF” on one side and “15” on the reverse.

Bottle of 30..............................NDC 0430-0171-15
Bottle of 90..............................NDC 0430-0171-23

Storage

Store at 25° C (77° F); excursions permitted to 15 to 30° C (59 to 86° F) [see USP Controlled Room Temperature]. Protect from light.

Keep this and all drugs out of the reach of children.

Manufactured by: Novartis Pharma Stein AG, Stein, Switzerland for Warner Chilcott Company, LLC Fajardo, Puerto Rico 00738. Marketed by: Warner Chilcott (US), LLC Rockaway, NJ 07866 1-800-521-8813

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Enablex was evaluated in controlled clinical trials in a total of 8,830 patients, 6,001 of whom were treated with Enablex. Of this total, 1,069 patients participated in three, 12-week, randomized, placebo-controlled, fixed-dose efficacy and safety studies (Studies 1, 2 and 3). Of this total, 337 and 334 patients received Enablex 7.5 mg daily and 15 mg daily, respectively. In all long-term trials combined, 1,216 and 672 patients received treatment with Enablex for at least 24 and 52 weeks, respectively.

In Studies 1, 2 and 3 combined, the serious adverse reactions to Enablex were urinary retention and constipation.

In Studies 1, 2 and 3 combined, dry mouth leading to study discontinuation occurred in 0 percent, 0.9 percent, and 0 percent of patients treated with Enablex 7.5 mg daily, Enablex 15 mg daily and placebo, respectively. Constipation leading to study discontinuation occurred in 0.6 percent, 1.2 percent, and 0.3 percent of patients treated with Enablex 7.5 mg daily, Enablex 15 mg daily and placebo, respectively.

Table 1 lists the rates of identified adverse reactions, derived from all reported adverse events in 2 percent or more of patients treated with 7.5 mg or 15 mg Enablex, and greater than placebo in Studies 1, 2 and 3. In these studies, the most frequently reported adverse reactions were dry mouth and constipation. The majority of the adverse reactions were mild or moderate in severity and most occurred during the first two weeks of treatment.

Table 1: Incidence of Identified Adverse Reactions, Derived from All Adverse Events Reported in ≥ 2 Percent of Patients Treated with Enablex Extended-Release Tablets and More Frequent with Enablex than with Placebo in Studies 1, 2, and 3

Body System Adverse Reaction Percentage of Subjects
Enablex 7.5 mg
N = 337
Enablex 15 mg
N = 334
Placebo
N = 388
Digestive 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
Urogenital Urinary Tract Infection 4.7 4.5 2.6
Nervous Dizziness 0.9 2.1 1.3
Body as a Whole Asthenia 1.5 2.7 1.3
Eye Dry Eyes 1.5 2.1 0.5

Other adverse reactions reported by 1 percent to 2 percent of Enablex-treated patients include: abnormal vision, accidental injury, back pain, dry skin, flu syndrome, hypertension, vomiting, peripheral edema, weight gain, arthralgia, bronchitis, pharyngitis, rhinitis, sinusitis, rash, pruritus, urinary tract disorder and vaginitis.

Study 4 was a randomized, 12-week, placebo-controlled, dose-titration regimen study in which Enablex was administered in accordance with dosing recommendations [see DOSAGE AND ADMINISTRATION]. All patients initially received placebo or Enablex 7.5 mg daily, and after two weeks, patients and physicians were allowed to adjust upward to Enablex 15 mg if needed. In this study, the most commonly reported adverse reactions were also constipation and dry mouth. Table 2 lists the identified adverse reactions, derived from all adverse events reported in > 3 percent of patients treated with Enablex and greater than placebo.

Table 2: Number (Percent) of Adverse Reactions, Derived from All Adverse Events Reported in > 3 Percent of Patients Treated with Enablex Extended-Release Tablets, and More Frequent with Enablex than Placebo, in Study 4

Adverse Reaction Enablex 7.5 mg/15 mg
N = 268
Placebo
N = 127
Constipation 56 (20.9 percent) 10 (7.9 percent)
Dry Mouth 50 (18.7 percent) 11 (8.7 percent)
Headache 18 (6.7 percent) 7 (5.5 percent)
Dyspepsia 12 (4.5 percent) 2 (1.6 percent)
Nausea 11 (4.1 percent) 2 (1.6 percent)
Urinary Tract Infection 10 (3.7 percent) 4 (3.1 percent)
Accidental Injury 8 (3.0 percent) 3 (2.4 percent)
Flu Syndrome 8 (3.0 percent) 3 (2.4 percent)

Post Marketing Experience

The following adverse reactions have been reported during post approval use of Enablex extended-release tablets (darifenacin). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency or establish a causal relationship to drug exposure.

Dermatologic: erythema multiforme, interstitial granuloma annulare

General: hypersensitivity reactions, including angioedema with airway obstruction and anaphylactic reaction

Central Nervous: confusion, hallucinations and somnolence

Cardiovascular: palpitations and syncope

Read the Enablex (darifenacin extended-release tablets) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

CYP3A4 Inhibitors

The systemic exposure of darifenacin from Enablex extended-release tablets is increased in the presence of CYP3A4 inhibitors. The daily dose of Enablex should not exceed 7.5 mg when co-administered with potent CYP3A4 inhibitors (for example, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone). No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (for example, erythromycin, fluconazole, diltiazem and verapamil) [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

CYP2D6 Inhibitors

No dosing adjustments are recommended in the presence of CYP2D6 inhibitors (for example, paroxetine, fluoxetine, quinidine and duloxetine) [see CLINICAL PHARMACOLOGY].

CYP2D6 Substrates

Caution should be taken when Enablex is used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window (for example, flecainide, thioridazine and tricyclic antidepressants) [see CLINICAL PHARMACOLOGY].

CYP3A4 Substrates

Darifenacin (30 mg daily) did not have a significant impact on midazolam (7.5 mg) pharmacokinetics [see CLINICAL PHARMACOLOGY].

Combination oral contraceptives

Darifenacin (10 mg three times daily) had no effect on the pharmacokinetics of the combination oral contraceptives containing levonorgestrel and ethinyl estradiol [see CLINICAL PHARMACOLOGY].

Warfarin

Darifenacin had no significant effect on prothrombin time when a single dose of warfarin 30 mg was coadministered with darifenacin (30 mg daily) at steady-state. Standard therapeutic prothrombin time monitoring for warfarin should be continued.

Digoxin

Darifenacin (30 mg daily) did not have a clinically relevant effect on the pharmacokinetics of digoxin (0.25 mg) at steady-state. Routine therapeutic drug monitoring for digoxin should be continued [see CLINICAL PHARMACOLOGY].

Other Anticholinergic Agents

The concomitant use of Enablex with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision and other anticholinergic pharmacological effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to effects on gastrointestinal motility.

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Risk of Urinary Retention

Enablex should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.

Decreased Gastrointestinal Motility

Enablex should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention. Enablex, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as severe constipation, ulcerative colitis, and myasthenia gravis.

Controlled Narrow-Angle Glaucoma

Enablex should be used with caution in patients being treated for narrow-angle glaucoma and only where the potential benefits outweigh the risks.

Angioedema

Angioedema of the face, lips, tongue, and/or larynx have been reported with darifenacin. In some cases angioedema occurred after the first dose. Angioedema associated with upper airway swelling may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, darifenacin should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.

Central Nervous System Effects

Enablex is associated with anticholinergic central nervous system (CNS) effects [see ADVERSE REACTIONS]. A variety of CNS anticholinergic effects have been reported, including headache, confusion, hallucinations and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how Enablex affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.

Patients with Hepatic Impairment

The daily dose of Enablex should not exceed 7.5 mg for patients with moderate hepatic impairment (Child-Pugh B). Enablex has not been studied in patients with severe hepatic impairment (Child-Pugh C) and therefore is not recommended for use in this patient population [see DOSAGE AND ADMINISTRATION, Use In Specific Populations and CLINICAL PHARMACOLOGY].

Patient Counseling Information

“See FDA-approved patient labeling (PATIENT INFORMATION)

Patients should be informed that anticholinergic agents, such as Enablex, may produce clinically significant adverse effects related to anticholinergic pharmacological activity including constipation, urinary retention and blurred vision. Heat prostration (due to decreased sweating) can occur when anticholinergics such as Enablex are used in a hot environment. Because anticholinergics, such as Enablex, may produce dizziness or blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug's effects have been determined. Patients should read the patient information leaflet before starting therapy with Enablex.

Patients should be informed that darifenacin may produce clinically significant angioedema that may result in airway obstruction. 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 extended-release tablets should be taken once daily with water. They may be taken with or without food, and should be swallowed whole and not chewed, divided or crushed.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies with darifenacin were conducted in mice and rats. No evidence of drug-related carcinogenicity was revealed in a 24-month study in mice at dietary doses up to 100 mg/kg/day or approximately 32 times the estimated free plasma AUC reached at the maximum recommended human dose (the AUC at the MRHD) of 15 mg and in a 24-month study in rats at doses up to 15 mg/kg/day or up to approximately 12 times the AUC at the MRHD in female rats and approximately eight times the AUC at the MRHD in male rats.

Darifenacin was not genotoxic in the bacterial mutation assay (Ames test), the Chinese hamster ovary assay, the human lymphocyte assay, or the in vivo mouse bone marrow cytogenetics assay.

There was no evidence for effects on fertility in male or female rats treated at oral doses up to approximately 78 times (50 mg/kg/day) the AUC at the MRHD.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no studies of darifenacin in pregnant women.

Darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 times and 28 times, respectively (doses up to 50 and 30 mg/kg/day, respectively) the maximum recommended human dose [MRHD] of 15 mg. At approximately 59 times the MRHD in rats, there was a delay in the ossification of the sacral and caudal vertebrae which was not observed at approximately 13 times the AUC. Dystocia was observed in dams at approximately 17 times the AUC (10 mg/kg/day). Slight developmental delays were observed in pups at this dose. At five times the AUC (3 mg/kg/day), there were no effects on dams or pups. In rabbits, an exposure approximately 28 times (30 mg/kg/day) the MRHD of darifenacin was shown to increase post-implantation loss, with a no effect level at nine times (10 mg/kg/day) the AUC at the MRHD. Dilated ureter and/or kidney pelvis was also observed in offspring at this dose along with urinary bladder dilation consistent with the pharmacological action of darifenacin, with one case observed at nine times (10 mg/kg/day). No effect was observed at approximately 2.8 times (3 mg/kg/day) the AUC at the MRHD.

Because animal reproduction studies are not always predictive of human response, Enablex should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

Nursing Mothers

Darifenacin is excreted into the milk of rats. It is not known whether darifenacin is excreted into human milk and therefore caution should be exercised before Enablex is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Enablex in pediatric patients have not been established.

Geriatric Use

In the fixed-dose, placebo-controlled, clinical studies, 30 percent of patients treated with Enablex were over 65 years of age. No overall differences in safety or efficacy were observed between patients over 65 years (n = 207) and younger patients < 65 years (n = 464). No dose adjustment is recommended for elderly patients [see CLINICAL PHARMACOLOGY and Clinical Studies].

Hepatic Impairment

Subjects with severe hepatic impairment (Child-Pugh C) have not been studied, therefore Enablex is not recommended for use in these patients [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. The daily dose of Enablex should not exceed 7.5 mg once daily for patients with moderate hepatic impairment (Child-Pugh B) [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. After adjusting for plasma protein binding, unbound darifenacin exposure was estimated to be 4.7-fold higher in subjects with moderate hepatic impairment than subjects with normal hepatic function. No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A).

Renal Impairment

A study of subjects with varying degrees of renal impairment (creatinine clearance between 10 and 136 mL/min) demonstrated no clear relationship between renal function and darifenacin clearance. No dose adjustment is recommended for patients with renal impairment [see CLINICAL PHARMACOLOGY].

Gender

No dose adjustment is recommended based on gender [see CLINICAL PHARMACOLOGY and Clinical Studies].

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Overdosage with antimuscarinic agents, including Enablex, can result in severe antimuscarinic effects. Treatment should be symptomatic and supportive. In the event of overdosage, ECG monitoring is recommended. Enablex has been administered in clinical trials at doses up to 75 mg (five times the maximum therapeutic dose) and signs of overdose were limited to abnormal vision.

CONTRAINDICATIONS

Enablex is contraindicated in patients with, or at risk for, the following conditions:

  • urinary retention
  • gastric retention, or
  • uncontrolled narrow-angle glaucoma.

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Darifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of the urinary bladder smooth muscle and stimulation of salivary secretion.

In vitro studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9- and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs.

Pharmacodynamics

In three cystometric studies performed in patients with involuntary detrusor contractions, increased bladder capacity was demonstrated by an increased volume threshold for unstable contractions and diminished frequency of unstable detrusor contractions after Enablex treatment. These findings are consistent with an antimuscarinic action on the urinary bladder.

Electrophysiology

The effect of six-day treatment of 15 mg and 75 mg Enablex on QT/QTc interval was evaluated in a multiple-dose, double-blind, randomized, placebo- and active-controlled (moxifloxacin 400 mg) parallel-arm design study in 179 healthy adults (44 percent male, 56 percent female) aged 18 to 65. Subjects included 18 percent poor metabolizer (PMs) and 82 percent extensive metabolizer (EMs). The QT interval was measured over a 24-hour period both predosing and at steady-state. The 75 mg Enablex dose was chosen because this achieves exposure similar to that observed in CYP2D6 poor metabolizers administered the highest recommended dose (15 mg) of darifenacin in the presence of a potent CYP3A4 inhibitor. At the doses studied, Enablex did not result in QT/QTc interval prolongation at any time during the steady-state, while moxifloxacin treatment resulted in a mean increase from baseline QTcF of about 7.0 msec when compared to placebo. In this study, darifenacin 15 mg and 75 mg doses demonstrated a mean heart rate change of 3.1 and 1.3 bpm, respectively, when compared to placebo. However, in the clinical efficacy and safety studies, the change in median HR following treatment with Enablex was no different from placebo.

Pharmacokinetics

Absorption

After oral administration of Enablex to healthy volunteers, peak plasma concentrations of darifenacin are reached approximately seven hours after multiple dosing and steady-state plasma concentrations are achieved by the sixth day of dosing. The mean (SD) steady-state time course of Enablex 7.5 mg and 15 mg extended-release tablets is depicted in Figure 1.

Figure 1 : Mean (SD) Steady-State Darifenacin Plasma Concentration-Time Profiles for Enablex 7.5 mg and 15 mg in Healthy Volunteers Including Both CYP2D6 EMs and PMs*

Mean (SD) Steady-State Darifenacin Plasma Concentration - Illustration

A summary of mean (standard deviation, SD) steady-state pharmacokinetic parameters of Enablex 7.5 mg and 15 mg extended-release tablets in EMs and PMs of CYP2D6 is provided in Table 3.

Table 3: Mean (SD) Steady-State Pharmacokinetic Parameters from Enablex 7.5 mg and 15 mg Extended-Release Tablets Based on Pooled Data by Predicted CYP2D6 Phenotype

Enablex 7.5 mg
(N = 68 EM, 5 PM)
Enablex 15 mg
(N = 102 EM, 17 PM)
  AUC24 (ng•h/mL) Cmax (ng/mL) Cavg (ng/mL) Tmax (h) t½ (h) AUC24 (ng•h/mL) Cmax (ng/mL) Cavg (ng/mL) Tmax (h) t½ (h)
EM 29.24 (15.47) 2.01 (1.04) 1.22 (0.64) 6.49 (4.19) 12.43 (5.64)a 88.90 (67.87) 5.76 (4.24) 3.70 (2.83) 7.61 (5.06) 12.05 (12.37)b
PM 67.56 (13.13) 4.27 (0.98) 2.81 (0.55) 5.20 (179) 19.95c 157.71 (77.08) 9.99 (5.09) 6.58 (3.22) 6.71 (3.58) 7.40d
aN = 25; bN = 8; cN = 2; dN = 1; AUC24 = Area under the plasma concentration versus time curve for 24h;
Cmax = Maximum observed plasma concentration; Cavg = Average plasma concentration at steady-state;
Tmax = Time of occurrence of Cmax; t½ = Terminal elimination half-life. Regarding EM and PM [see CLINICAL PHARMACOLOGY, Pharmacokinetics, Variability in Metabolism].

The mean oral bioavailability of Enablex in EMs at steady-state is estimated to be 15 percent and 19 percent for 7.5 mg and 15 mg tablets, respectively.

Effect of Food

Following single dose administration of Enablex with food, the AUC of darifenacin was not affected, while the Cmax was increased by 22 percent and Tmax was shortened by 3.3 hours. There is no effect of food on multiple-dose pharmacokinetics from Enablex.

Distribution

Darifenacin is approximately 98 percent bound to plasma proteins (primarily to alpha-1-acid-glycoprotein). The steady-state volume of distribution (Vss) is estimated to be 163 L.

Metabolism

Darifenacin is extensively metabolized by the liver following oral dosing.

Metabolism is mediated by cytochrome P450 enzymes CYP2D6 and CYP3A4. The three main metabolic routes are as follows:

  1. monohydroxylation in the dihydrobenzofuran ring;
  2. dihydrobenzofuran ring opening;
  3. N-dealkylation of the pyrrolidine nitrogen.

The initial products of the hydroxylation and N-dealkylation pathways are the major circulating metabolites but they are unlikely to contribute significantly to the overall clinical effect of darifenacin.

Variability in Metabolism

A subset of individuals (approximately 7 percent Caucasians and 2 percent African Americans) are poor metabolizers (PMs) of CYP2D6 metabolized drugs. Individuals with normal CYP2D6 activity are referred to as extensive metabolizers (EMs). The metabolism of darifenacin in PMs will be principally mediated via CYP3A4. The darifenacin ratios (PM versus EM) for Cmax and AUC following darifenacin 15 mg once daily at steady-state were 1.9 and 1.7, respectively.

Excretion

Following administration of an oral dose of 14C-darifenacin solution to healthy volunteers, approximately 60 percent of the radioactivity was recovered in the urine and 40 percent in the feces. Only a small percentage of the excreted dose was unchanged darifenacin (3 percent). Estimated darifenacin clearance is 40 L/h for EMs and 32 L/h for PMs. The elimination half-life of darifenacin following chronic dosing is approximately 13 to 19 hours.

Drug-Drug Interactions

Effects of Other Drugs on Darifenacin

Darifenacin metabolism is primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4. Therefore, inducers of CYP3A4 or inhibitors of either of these enzymes may alter darifenacin pharmacokinetics [see DRUG INTERACTIONS].

CYP3A4 Inhibitors: In a drug interaction study, when a 7.5 mg once daily dose of Enablex was given to steady-state and co-administered with the potent CYP3A4 inhibitor ketoconazole 400 mg, mean darifenacin Cmax increased to 11.2 ng/mL for EMs (n = 10) and 55.4 ng/mL for one PM subject (n = 1). Mean AUC increased to 143 and 939 ng•h/mL for EMs and for one PM subject, respectively. When a 15 mg daily dose of Enablex was given with ketoconazole, mean darifenacin Cmax increased to 67.6 ng/mL and 58.9 ng/mL for EMs (n = 3) and one PM subject (n = 1), respectively. Mean AUC increased to 1110 and 931 ng•h/mL for EMs and for one PM subject, respectively [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS].

The mean Cmax and AUC of darifenacin following 30 mg once daily dosing at steady-state were 128 percent and 95 percent higher, respectively, in the presence of a moderate CYP3A4 inhibitor, erythromycin. Co-administration of fluconazole, a moderate CYP3A4 inhibitor and darifenacin 30 mg once daily at steady-state increased darifenacin Cmax and AUC by 88 percent and 84 percent, respectively [see DRUG INTERACTIONS].

The mean Cmax and AUC of darifenacin following 30 mg once daily at steady-state were 42 percent and 34 percent higher, respectively, in the presence of cimetidine, a mixed CYP P450 enzyme inhibitor.

CYP2D6 Inhibitors: Darifenacin exposure following 30 mg once daily at steady-state was 33 percent higher in the presence of the potent CYP2D6 inhibitor paroxetine 20 mg [see DRUG INTERACTIONS].

Effects of Darifenacin on Other Drugs

In Vitro Studies: Based on in vitro human microsomal studies, Enablex is not expected to inhibit CYP1A2 or CYP2C9 at clinically relevant concentrations.

In Vivo Studies: The potential for clinical doses of Enablex to act as inhibitors of CYP2D6 or CYP3A4 substrates was investigated in specific drug interaction studies.

CYP2D6 Substrates: The mean Cmax and AUC of imipramine, a CYP2D6 substrate, were increased by 57 percent and 70 percent, respectively, in the presence of steady-state darifenacin 30 mg once daily. The mean Cmax and AUC of desipramine, the active metabolite of imipramine, were increased by 260 percent [see DRUG INTERACTIONS].

CYP3A4 Substrates: Darifenacin (30 mg daily) co-administered with a single oral dose of midazolam 7.5 mg resulted in a 17 percent increase in midazolam exposure.

Combination Oral Contraceptives: Darifenacin (10 mg three times daily) had no effect on the pharmacokinetics of a combination oral contraceptive containing levonorgestrel (0.15 mg) and ethinyl estradiol (0.03 mg).

Warfarin: Darifenacin had no significant effect on prothrombin time when a single dose of warfarin 30 mg was co-administered with darifenacin (30 mg daily) at steady-state [see DRUG INTERACTIONS].

Digoxin: Darifenacin (30 mg daily) co-administered with digoxin (0.25 mg) at steady-state resulted in a 16 percent increase in digoxin exposure [see DRUG INTERACTIONS].

Pharmacokinetics in Special Populations

Age: A population pharmacokinetic analysis of patient data indicated a trend for clearance of darifenacin to decrease with age (6 percent per decade relative to a median age of 44). Following administration of Enablex 15 mg once daily, darifenacin exposure at steady-state was approximately 12 percent to 19 percent higher in volunteers between 45 and 65 years of age compared to younger volunteers aged 18 to 44 years [see Use In Specific Populations].

Pediatric: The pharmacokinetics of Enablex has not been studied in the pediatric population [see Use In Specific Populations].

Gender: PK parameters were calculated for 22 male and 25 female healthy volunteers. Darifenacin Cmax and AUC at steady-state were approximately 57 percent to 79 percent and 61 percent to 73 percent higher in females than in males, respectively [see Use In Specific Populations].

Renal Impairment: A study of subjects with varying degrees of renal impairment (creatinine clearance between 10 and 136 mL/min) given Enablex 15 mg once daily to steady-state demonstrated no clear relationship between renal function and darifenacin clearance [see Use in Specific Populations].

Hepatic Impairment: Enablex pharmacokinetics were investigated in subjects with mild (Child-Pugh A) or moderate (Child-Pugh B) impairment of hepatic function given Enablex 15 mg once daily to steady-state. Mild hepatic impairment had no effect on the pharmacokinetics of darifenacin. However, protein binding of darifenacin was affected by moderate hepatic impairment. After adjusting for plasma protein binding, unbound darifenacin exposure was estimated to be 4.7-fold higher in subjects with moderate hepatic impairment than subjects with normal hepatic function. Subjects with severe hepatic impairment (Child-Pugh C) have not been studied [see DOSAGE AND ADMINISTRATION, WARNING AND PRECAUTIONS and Use in Specific Population].

Clinical Studies

Enablex extended-release tablets were evaluated for the treatment of patients with overactive bladder with symptoms of urgency, urge urinary incontinence, and increased urinary frequency in three randomized, fixed-dose, placebo-controlled, multicenter, double-blind, 12-week studies (Studies 1, 2 and 3) and one randomized, double-blind, placebo-controlled, multicenter, dose-titration study (Study 4). For study eligibility in all four studies, patients with symptoms of overactive bladder for at least six months were required to demonstrate at least eight micturitions and at least one episode of urinary urgency per day, and at least five episodes of urge urinary incontinence per week. The majority of patients were white (94 percent) and female (84 percent), with a mean age of 58 years, range 19 to 93 years. Thirty-three percent of patients were > 65 years of age. These characteristics were well balanced across treatment groups. The study population was inclusive of both naïve patients who had not received prior pharmacotherapy for overactive bladder (60 percent) and those who had (40 percent).

Table 4 shows the efficacy data collected from 7- or 14-day voiding diaries in the three fixed-dose placebo-controlled studies of 1,059 patients treated with placebo, 7.5 mg or 15 mg once daily Enablex for 12 weeks. A significant decrease in the primary endpoint, change from baseline in average weekly urge urinary incontinence episodes was observed in all three studies. Data is also shown for two secondary endpoints, change from baseline in the average number of micturitions per day (urinary frequency) and change from baseline in the average volume voided per micturition.

Table 4: Difference Between Enablex (7.5 mg, 15 mg) and Placebo for the Week 12 Change from Baseline (Studies 1, 2 and 3)

  Study 1 Study 2 Study 3
Enablex 7.5 mg Enablex 15 mg Placebo Enablex 7.5 mg Enablex 15 mg Placebo Enablex Placebo 15 mg  
No. of Patients Entered 229 115 164 108 107 109 112 115
Urge Incontinence Episodes per Week
  Median Baseline 16.3 17.0 16.6 14.0 17.3 1 6.1 16.2 15.5
  Median Change from Baseline -9.0 -10.4 -7.6 -8.1 -10.4 -5.9 -11.4 -9.0
  Median Difference to Placebo -1.5* -2.1* - * .8 2. - -4.3* - -2.4* -
Micturitions per Day
  Median Baseline 10.1 10.1 10.1 10.3 11.0 10.1 10.5 10.4
  Median Change from Baseline -1.6 -1.7 -0.8 -1.7 -1.9 -1.1 -1.9 -1.2
  Median Difference to Placebo -0.8* -0.9* - -0.5 -0.7* - -0.5 -
Volume of Urine Passed per Void (mL)
Median   Baseline 160.2 151.8 162.4 161.7 157.3 162.2 155.0 147.1
  Median Change from Baseline 14.9 30.9 7.6 16.8 23.6 7.1 26.7 4.6
  Median Difference to Placebo 9.1* 20.7* - 9.2 16.6* - 20.1* -
*Indicates statistically significant difference versus placebo (p < 0.05, Wilcoxon rank-sum test)

Table 5 shows the efficacy data from the dose-titration study in 395 patients who initially received 7.5 mg Enablex or placebo daily with the option to increase to 15 mg Enablex or placebo daily after two weeks.

Table 5: Difference between Enablex (7.5 mg/15 mg) and Placebo for the Week 12 Change from Baseline (Study 4)

  Enablex 7.5 mg /15 mg Placebo
No. of Patients Treated 268 127
Urge Incontinence Episodes per Week
Median Baseline 16.0 14.0
Median Change from Baseline -8.2 -6.0
Median Difference to Placebo -1.4* -
Micturitions per Day
Median Baseline 9.9 10.4
Median Change from Baseline -1.9 -1.0
Median Difference to Placebo * .8 0. - -
Volume of Urine Passed per Void (mL)
Median Baseline 173.7 177.2
Median Change from Baseline 18.8 6.6
Median Difference to Placebo 13.3 * -
*Indicates statistically significant difference versus placebo (p < 0.05, Wilcoxon rank-sum test)

As seen in Figures 2 a, b and c, reductions in the number of urge incontinence episodes per week were observed within the first two weeks in patients treated with Enablex 7.5 mg and 15 mg once daily compared to placebo. Further, these effects were sustained throughout the 12-week treatment period.

Figures : 2a, 2b, 2c. Median Change from Baseline at Weeks 2, 6, 12 for Number of Urge Incontinence Episodes per Week (Studies 1, 2 and 3). Figure : 2a, Study 1

Comparative reductions in the number of urge incontinence episodes - Illustration

Figure : 2b, Study 2

Comparative reductions in the number of urge incontinence episodes - Illustration

Figure : 2c, Study 3

Comparative reductions in the number of urge incontinence episodes - Illustration

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Enablex®
(en-a-blex)
(darifenacin) extended-release tablets

Read this Patient Information leaflet about Enablex® before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your doctor about your medical condition or your treatment.

What is Enablex?

Enablex is a prescription medicine for adults used to treat the following symptoms due to a condition called overactive bladder:

  • Urge urinary incontinence: a strong need to urinate with leaking or wetting accidents
  • Urgency: a strong need to urinate right away
  • Frequency: urinating often

It is unknown if Enablex is safe and effective in children.

Who should not take Enablex?

Do not take Enablex if you:

  • are not able to empty your bladder (“urinary retention”)
  • have delayed or slow emptying of your stomach (“gastric retention”)
  • have an eye problem called “uncontrolled narrow-angle glaucoma

What should I tell my healthcare provider before starting Enablex?

Before starting Enablex, tell your doctor if you:

  • have trouble emptying your bladder or if you have a weak urine stream
  • have any stomach or intestinal problems, or problems with constipation
  • have liver problems
  • have any other medical conditions
  • are pregnant or are planning to become pregnant. It is not known if Enablex can harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Enablex passes into breast milk and if it can harm your baby. Talk to your doctor about the best way to feed your baby if you take Enablex.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Enablex and certain other medicines may affect each other, causing side effects.

Especially tell your healthcare provider if you take a:

  • antifungal medicine ketoconazole (Nizoral®) or itraconazole (Sporanox®)
  • antibiotic medicine clarithromycin (Biaxin®)
  • anti-HIV medicine ritonavir (Norvir®) or nelfinavir (Viracept®)
  • medicine to treat depression nefazadone (Serzone®)
  • medicine to treat an abnormal heartbeat flecainide (Tambocor™)
  • antipsychotic medicine thioridazine (Mellaril®)
  • medicine to treat depression called a tricyclic antidepressant

Know all the medicines you take. Keep a list of them with you to show your doctor and pharmacist each time you get a new medicine.

How should I take Enablex?

  • Take Enablex exactly as prescribed. Your doctor will prescribe the dose that is right for you. Take Enablex 1 time daily with water.
  • Enablex should be swallowed whole. Do not chew, cut or crush Enablex tablet.
  • Enablex may be taken with or without food.
  • If you take too much Enablex call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking Enablex?

Enablex can cause blurred vision or dizziness. Do not drive or operate heavy machinery until you know how Enablex affects you.

What are the possible side effects of Enablex?

Enablex may cause serious side effects including:

  • Serious allergic reaction. Stop taking Enablex and get medical help right away if you have:
    • hives, skin rash or swelling
    • severe itching
    • swelling of your face, mouth or tongue
    • trouble breathing

The most common side effects with Enablex are:

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Enablex. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store Enablex?

  • Store Enablex at room temperature, between 59° F to 86° F (15° C to 30° C).
  • Keep Enablex out of the light.

Keep Enablex and all medicines out of the reach of children.

General information about Enablex.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Enablex for a condition for which it was not prescribed. Do not give Enablex to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about Enablex. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Enablex that is written for health professionals.

What are the ingredients in Enablex?

Active ingredient: darifenacin

Inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose, magnesium stearate, polyethylene glycol, talc, titanium dioxide. The 15 mg tablet also contains iron oxide red and iron oxide yellow.

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Enablex®
(en-a-blex)
(darifenacin) extended-release tablets

Read this Patient Information leaflet about Enablex® before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your doctor about your medical condition or your treatment.

What is Enablex?

Enablex is a prescription medicine for adults used to treat the following symptoms due to a condition called overactive bladder:

  • Urge urinary incontinence: a strong need to urinate with leaking or wetting accidents
  • Urgency: a strong need to urinate right away
  • Frequency: urinating often

It is unknown if Enablex is safe and effective in children.

Who should not take Enablex?

Do not take Enablex if you:

  • are not able to empty your bladder (“urinary retention”)
  • have delayed or slow emptying of your stomach (“gastric retention”)
  • have an eye problem called “uncontrolled narrow-angle glaucoma

What should I tell my healthcare provider before starting Enablex?

Before starting Enablex, tell your doctor if you:

  • have trouble emptying your bladder or if you have a weak urine stream
  • have any stomach or intestinal problems, or problems with constipation
  • have liver problems
  • have any other medical conditions
  • are pregnant or are planning to become pregnant. It is not known if Enablex can harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Enablex passes into breast milk and if it can harm your baby. Talk to your doctor about the best way to feed your baby if you take Enablex.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Enablex and certain other medicines may affect each other, causing side effects.

Especially tell your healthcare provider if you take a:

  • antifungal medicine ketoconazole (Nizoral®) or itraconazole (Sporanox®)
  • antibiotic medicine clarithromycin (Biaxin®)
  • anti-HIV medicine ritonavir (Norvir®) or nelfinavir (Viracept®)
  • medicine to treat depression nefazadone (Serzone®)
  • medicine to treat an abnormal heartbeat flecainide (Tambocor™)
  • antipsychotic medicine thioridazine (Mellaril®)
  • medicine to treat depression called a tricyclic antidepressant

Know all the medicines you take. Keep a list of them with you to show your doctor and pharmacist each time you get a new medicine.

How should I take Enablex?

  • Take Enablex exactly as prescribed. Your doctor will prescribe the dose that is right for you. Take Enablex 1 time daily with water.
  • Enablex should be swallowed whole. Do not chew, cut or crush Enablex tablet.
  • Enablex may be taken with or without food.
  • If you take too much Enablex call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking Enablex?

Enablex can cause blurred vision or dizziness. Do not drive or operate heavy machinery until you know how Enablex affects you.

What are the possible side effects of Enablex?

Enablex may cause serious side effects including:

  • Serious allergic reaction. Stop taking Enablex and get medical help right away if you have:
    • hives, skin rash or swelling
    • severe itching
    • swelling of your face, mouth or tongue
    • trouble breathing

The most common side effects with Enablex are:

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Enablex. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store Enablex?

  • Store Enablex at room temperature, between 59° F to 86° F (15° C to 30° C).
  • Keep Enablex out of the light.

Keep Enablex and all medicines out of the reach of children.

General information about Enablex.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Enablex for a condition for which it was not prescribed. Do not give Enablex to other people, even if they have the same symptoms you have. It may harm them.

This Patient Information leaflet summarizes the most important information about Enablex. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Enablex that is written for health professionals.

What are the ingredients in Enablex?

Active ingredient: darifenacin

Inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose, magnesium stearate, polyethylene glycol, talc, titanium dioxide. The 15 mg tablet also contains iron oxide red and iron oxide yellow.

Last reviewed on RxList: 3/22/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Enablex Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

DARIFENACIN EXTENDED-RELEASE - ORAL

(dar-e-fen-A-sin)

COMMON BRAND NAME(S): Enablex

USES: This medication is used to treat an overactive bladder. By relaxing the muscles in the bladder, darifenacin improves your ability to control your urination. It helps to reduce leaking of urine, feelings of needing to urinate right away, and frequent trips to the bathroom. This medication belongs to the class of drugs known as antispasmodics.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using darifenacin and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.

Take this medication by mouth, with or without food, usually once a day, or as directed by your doctor. Swallow this medication with a full glass of water (8 ounces/240 milliliters).

Do not crush or chew extended-release tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day. Dosage is based on your medical condition (especially liver disease), response to therapy, and use of certain interacting medicines. Consult your doctor or pharmacist for more details.

Do not increase your dose or take this medication more often without your doctor's approval. Your condition will not improve any faster and the risk of serious side effects may be increased.

Inform your doctor if your condition does not improve or if it worsens.

Disclaimer

Enablex Consumer (continued)

SIDE EFFECTS: Dry mouth, constipation, nausea, stomach upset, stomach pain, blurred vision, dry eyes, dizziness, or weakness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use a saliva substitute.

To prevent constipation, maintain a diet adequate in fiber, drink plenty of water, and exercise. If you become constipated, consult your pharmacist for help in choosing a laxative (e.g., stimulant-type with stool softener).

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: severe stomach/abdominal pain, constipation for 3 or more days, difficulty urinating, signs of kidney infection (e.g., burning/painful urination, lower back pain, fever), mental/mood changes (such as confusion, hallucinations).

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Enablex (darifenacin extended-release tablets) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking darifenacin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: problems emptying your bladder (urinary retention), severe blockage of stomach/intestines (gastric retention), a certain eye condition (uncontrolled narrow angle glaucoma), severe liver disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other bladder problems (e.g., bladder outflow obstruction), stomach/intestinal disease (e.g., ulcerative colitis), slowed movement of stomach/intestines, severe constipation, controlled narrow angle glaucoma, liver disease, enlarged prostate, a certain muscle disease (myasthenia gravis).

This drug may cause dizziness or blurred vision. Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely. Limit alcoholic beverages.

This medication can cause decreased sweating. Avoid becoming overheated in hot weather, saunas, or during exercise or other strenuous activities since heatstroke may occur.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Enablex Consumer (continued)

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because very serious interactions may occur: pramlintide.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting darifenacin.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: potassium tablets/capsules, other drugs that can cause dry mouth and constipation (e.g., anticholinergic medications such as atropine, antihistamines including diphenhydramine and scopolamine, other antispasmodics including dicyclomine, belladonna alkaloids), drugs affecting liver enzymes that remove darifenacin from your body (such as azole antifungals including itraconazole; macrolide antibiotics including clarithromycin; ritonavir; nelfinavir; nefazodone; rifamycins including rifabutin; St. John's wort; certain anti-seizure medicines including carbamazepine).

This drug can slow down the removal of other drugs from your body by affecting certain liver enzymes. These affected drugs include: flecainide, thioridazine, tricyclic antidepressants (e.g., amitriptyline, imipramine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include fast/irregular heartbeat, agitation.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised April 2012. Copyright(c) 2012 First Databank, Inc.

Enablex Patient Information Including Side Effects

Brand Names: Enablex

Generic Name: darifenacin (Pronunciation: dar e FEN a sin)

What is darifenacin (Enablex)?

Darifenacin reduces muscle spasms of the bladder and urinary tract.

Darifenacin is used to treat symptoms of overactive bladder, such as frequent or urgent urination, and incontinence (urine leakage).

Darifenacin may also be used for other purposes not listed in this medication guide.

Enablex 15 mg

round, peach, imprinted with DF, 15

Enablex 7.5 mg

round, white, imprinted with DF, 7.5

What are the possible side effects of darifenacin (Enablex)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using darifenacin and call your doctor at once if you have any of these serious side effects:

  • hot, dry skin and extreme thirst;
  • severe stomach pain or constipation;
  • pain or burning when you urinate; or
  • urinating less than usual or not at all.

Less serious side effects may include:

  • dry mouth;
  • dry eyes, blurred vision;
  • mild constipation;
  • diarrhea;
  • nausea, mild stomach pain or upset;
  • dizziness, weakness;
  • headache; or
  • fever, sore throat, body aches, or other flu symptoms.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Enablex (darifenacin extended-release tablets) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about darifenacin (Enablex)?

You should not use this medication if you are allergic to darifenacin, or if you have untreated or uncontrolled narrow-angle glaucoma, a blockage in your digestive tract (stomach or intestines), or if you are unable to urinate.

Before using darifenacin, tell your doctor if you have glaucoma, liver disease, a muscle disorder, ulcerative colitis, or a blockage in your stomach or intestines.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Darifenacin can decrease perspiration and you may be more prone to heat stroke.

Darifenacin can cause side effects that may impair your vision or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Stop using this medication and call your doctor if you have serious side effects such as hot and dry skin, extreme thirst, severe stomach pain or constipation, pain or burning when you urinate, or if you stop urinating.

Side Effects Centers

Enablex Patient Information including How Should I Take

What should I discuss with my health care provider before taking darifenacin (Enablex)?

You should not use this medication if you are allergic to darifenacin, or have certain conditions. Be sure your doctor knows if you have:

  • untreated or uncontrolled narrow-angle glaucoma;
  • a stomach disorder causing delayed emptying; or
  • if you are unable to urinate.

Before using darifenacin, tell your doctor if you are allergic to any drugs, or if you have:

  • glaucoma;
  • liver disease;
  • ulcerative colitis;
  • a blockage in your stomach or intestines; or
  • a muscle disorder such as myasthenia gravis.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take darifenacin.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether darifenacin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take darifenacin (Enablex)?

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Take this medicine with water.

Darifenacin can be taken with or without food.

Store darifenacin at room temperature away from moisture, heat, and light.

Side Effects Centers

Enablex Patient Information including If I Miss a Dose

What happens if I miss a dose (Enablex)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Enablex)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include severe constipation or stomach pain, extreme weakness, or urinating less than usual or not at all.

What should I avoid while taking darifenacin (Enablex)?

Avoid becoming overheated or dehydrated during exercise and in hot weather. Darifenacin can decrease perspiration and you may be more prone to heat stroke.

Darifenacin can cause side effects that may impair your vision or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

What other drugs will affect darifenacin (Enablex)?

The following drugs can interact with darifenacin. Tell your doctor if you are using any of these:

  • other bladder or urinary medications such as flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare); or
  • glycopyrrolate (Robinul);
  • flecainide (Tambocor);
  • mepenzolate (Cantil);
  • thioridazine (Mellaril);
  • HIV /AIDS medicine such as nelfinavir (Viracept) or ritonavir (Norvir);
  • an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., E-Mycin, Ery-Tab, Erythrocin), or troleandomycin (Tao);
  • an antifungal medication such as itraconazole (Sporanox) or ketoconazole (Nizoral);
  • atropine (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), methscopolamine (Pamine), or scopolamine (Transderm-Scop);
  • bronchodilators such as ipratroprium (Atrovent) or tiotropium (Spiriva);
  • irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Anaspaz, Cystospaz, Levsin, and others), or propantheline (Pro-Banthine); or
  • an antidepressant such as amitriptyline (Elavil, Etrafon), fluoxetine (Prozac), fluvoxamine (Luvox), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Janimine, Tofranil), nortriptyline (Pamelor), paroxetine (Paxil), and others.

This list is not complete and there may be other drugs that can interact with darifenacin. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about darifenacin.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 1.05. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

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