Enablex

Darifenacin comes as an extended-release (long-acting) tablet to take by mouth. It is usually taken once a day with plenty of liquid. This medication may be taken with or without food. Take darifenacin at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take darifenacin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the tablets whole; do not split, chew, or crush them.

Your doctor will start you on a low dose of darifenacin and may increase your dose after 2 weeks.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

You should not take Enablex if:

• you are unable to empty your bladder (urinary retention). 
• you have delayed or slow emptying of your stomach (gastric retention)
• you have an eye problem called "uncontrolled narrow-angle glaucoma"
• you are allergic to any ingredients in Enablex 

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

Heat exhaustion or heat stroke can happen when Enablex is used in hot environments. Symptoms of heat exhaustion may include:

• decreased sweating
• dizziness
• tiredness
• nausea
• increased body temperature

Grapefruit and grapefruit juice may interact with Enablex and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.
 

• Keep Enablex and all medicines out of the reach of children.
• Store Enablex at room temperature, 59 to 86ºF (15 to 30ºC). Protect from light.
• Safely dispose of Enablex that is out of date or no longer needed.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Genitourinary antispasmodic agent; an antimuscarinic agent.1

Overactive Bladder

Relief of symptoms associated with voiding (e.g., urge urinary incontinence, urgency, frequency).1

Extended-release darifenacin (15 mg once daily) may be as effective as immediate-release oxybutynin (5 mg 3 times daily).5

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Take this medicine only as directed. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects. Also, do not change your dose without checking first with your doctor.

This medicine comes with a patient information insert. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Swallow the extended-release tablet whole with water. Do not break, crush, or chew it. You may take this medicine with or without food.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • To treat bladder problems:
    • Adults—At first, 7.5 milligrams (mg) once a day. Your doctor may increase your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

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%) and female (84%), with a mean age of 58 years, range 19 to 93 years. Thirty-three percent of patients were greater than or equal to 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%) and those who had (40%).

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 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.

As seen in Figures 2 a, 2b and 2c, 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

Figure 2b, Study 2

Figure 2c, Study 3

N 0430-0171-15

Rx only

Enablex® (darifenacin) Extended-release tablets

15 mg* per tablet

30 Tablets

To report SUSPECTED ADVERSE REACTIONS,
contact Warner Chilcott at 1-800-521-8813
or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause vision problems.

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

Stop using Enablex and call your doctor at once if you have:

• severe stomach pain or constipation;

• confusion, hallucinations;

• little or no urinating;

• pain or burning when you urinate; or

• signs of dehydration--feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin.

Common Enablex side effects may include:

• nausea, indigestion;

• constipation;

• headache, dizziness;

• dry mouth; or

• blurred vision.

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.

Applies to darifenacin: oral tablet extended release

Cardiovascular

Postmarketing reports: Palpitations, syncope[Ref]

Gastrointestinal

Very common (10% or more): Dry mouth (up to 35%), constipation (up to 21%)
Common (1% to 10%): Abdominal pain, nausea, dyspepsia, diarrhea
Uncommon (0.1% to 1%): Vomiting, flatulence, mouth ulceration, hyperhidrosis
Frequency not reported: Angioedema[Ref]

Dermatologic

Common (1% to 10%): Dry skin, pruritus, rash
Postmarketing reports: Erythema multiforme, interstitial granuloma annulare[Ref]

Respiratory

Common (1% to 10%): Nasal dryness, bronchitis, respiratory tract infection, pharyngitis
Uncommon (0.1% to 1%): Dyspnea, cough, rhinitis[Ref]

General

Most adverse events were mild or moderate and mostly occurred during the first 2 weeks of treatment.[Ref]

Genitourinary

Uncommon (0.1% to 1%): Urinary tract infection, urinary retention, urinary tract disorder, bladder pain, erectile dysfunction, vaginitis[Ref]

Metabolic

Uncommon (0.1% to 1%): Weight gain[Ref]

Hepatic

Uncommon (0.1% to 1%): Aspartate aminotransferase increased, alanine aminotransferase increased[Ref]

Hypersensitivity

Postmarketing reports: Generalized hypersensitivity reactions including angioedema[Ref]

Immunologic

Common (1% to 10%): Influenza syndrome[Ref]

Musculoskeletal

Common (1% to 10%): Back pain
Uncommon (0.1% to 1%): Arthralgia[Ref]

Nervous system

Very common (10% or more): Headache
Uncommon (0.1% to 1%): Dizziness, dysgeusia, somnolence[Ref]

Ocular

Common (1% to 10%): Dry eye
Uncommon (0.1% to 1%): Visual disturbance, blurred vision[Ref]

Other

Uncommon (0.1% to 1%): Edema, peripheral edema, face edema, asthenia, aspartate aminotransferase increased, alanine aminotransferase increased, accidental injury, pain[Ref]

Psychiatric

Uncommon (0.1% to 1%): Insomnia, abnormal thinking
Postmarketing reports: Depressed mood, altered mood, hallucination[Ref]

Some side effects of Enablex may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.