Enablex

Name: Enablex

Darifenacin Interactions

This medicine may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with darifenacin, especially:

  • clarithromycin;
  • flecainide;
  • thioridazine;
  • an antidepressant--amitriptyline, clomipramine, desipramine, doxepin, imipramine, nefazodone, nortriptyline;
  • antifungal medicine--itraconazole, ketoconazole; or
  • HIV or AIDS medicine--nelfinavir, ritonavir.

This list is not complete. Other drugs may interact with darifenacin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Darifenacin Dosage

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine with water.

Darifenacin can be taken with or without food.

Do not crush, chew, or break an extended-release tablet. Swallow it whole.

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

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

Overdose can cause vision problems.

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.

Patient Handout

Print without Office InfoPrint with Office Info

Side Effects of Enablex

The most common side effects with Enablex are:

  • dry mouth
  • constipation

Enablex may cause other less common side effects that include:

  • Swelling (angioedema) of the face, lips, tongue, and/or throat may occur. Stop taking Enablex and seek medical attention immediately if you experience swelling of the tongue or throat, or if you experience difficulty breathing. 
  • blurred vision. Use caution while driving or doing dangerous activities until you know how Enablex affects you.
  • heat exhaustion, or heat prostration. Heat prostration (due to decreased sweating) can occur when drugs such as Enablex are used in a hot environment.

These are not all the side effects with Enablex. For more information, ask your doctor, healthcare professional or pharmacist.

Enablex Usage

Take Enablex exactly as your doctor prescribes it. Your doctor will determine the best dose for you.

  • You should take Enablex once daily with water.
  • Enablex should be swallowed whole and not chewed, divided or crushed.
  • Enablex may be taken with or without food.
  • If you miss a dose of Enablex, begin taking Enablex again the next day. Do not take two doses of Enablex in the same day.
  • If you take too much Enablex, call your local Poison Control Center or emergency room right away.

Enablex Dosage

Take Enablex exactly as your doctor prescribes it. Follow the directions on your prescription bottle carefully. Your doctor will determine the best dose for you.

The recommended starting dose of Enablex is one 7.5 mg extended-release tablet once a day. The dose may be increased to 15 mg once a day, usually at least 2 weeks after starting Enablex.

If you have liver problems or are taking certain medicines in addition to Enablex, your doctor may keep you on the 7.5 mg dose.

Interactions for Enablex

Metabolized principally by CYP2D6 and CYP3A4.1 May inhibit CYP2D6 and CYP3A4; not expected to inhibit CYP1A2 and CYP2C9.1

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma darifenacin concentrations).1 7 Do not exceed 7.5 mg daily when used concomitantly with potent inhibitors of CYP3A4.1 No dosage adjustment required when used concomitantly with moderate CYP3A4 inhibitors.1 (See Specific Drugs under Interactions.)

Inhibitors of CYP2D6: Potential pharmacokinetic interaction (increased plasma darifenacin concentrations).1 However, no dosage adjustment required.1

Mixed inhibitors of CYP isoenzymes: Potential pharmacokinetic interaction (increased plasma darifenacin concentrations).1 However, no dosage adjustment required.8

Inducers of CYP3A4: Potential pharmacokinetic interaction1 (altered plasma darifenacin concentrations).1 8

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A4: Potential pharmacokinetic interaction (increased plasma substrate concentrations).1

Substrates of CYP2D6: Potential pharmacokinetic interaction (increased plasma substrate concentrations).1 Caution advised when used concomitantly with CYP2D6 substrates that have a narrow therapeutic index.1

Substrates of CYP1A2 or CYP2C9: Pharmacokinetic interaction not expected at therapeutic dosages.8

Drugs Affected by GI Motility

Potential pharmacokinetic interaction (altered absorption because of decreased GI motility).1 (See Decreased GI Motility under Cautions.)

Specific Drugs

Drug

Interaction

Comments

Anticholinergic agents

Possible additive anticholinergic effects (e.g., decreased GI motility; altered absorption of other drugs)1

Antidepressants, tricyclics

Possible increased concentrations of tricyclic antidepressant1

Use concomitantly with caution1

Cimetidine

Increased plasma darifenacin concentrations1

No dosage adjustment required1

Clarithromycin

Possible increased plasma darifenacin concentrations1

Do not exceed a darifenacin dosage of 7.5 mg daily1

Digoxin

Increased digoxin exposure1

Continue routine monitoring of digoxin therapy1

Diltiazem

Possible increased plasma darifenacin concentrations1

No dosage adjustment required1

Erythromycin

Increased plasma darifenacin concentrations1

No dosage adjustment required1

Flecainide

Possible increased flecainide concentrations1

Use concomitantly with caution1

Fluconazole

Increased plasma darifenacin concentrations1

No dosage adjustment required1

Hormonal contraceptives

Pharmacokinetic interaction unlikely with oral contraceptives containing ethinyl estradiol and levonorgestrel1

Imipramine

Increased plasma concentrations of imipramine and desipramine1

Itraconazole

Possible increased plasma darifenacin concentrations1

Do not exceed a darifenacin dosage of 7.5 mg daily1

Ketoconazole

Increased plasma darifenacin concentrations1

Do not exceed a darifenacin dosage of 7.5 mg daily1

Midazolam

Increased midazolam concentrations1

Nefazodone

Possible increased plasma darifenacin concentrations1

Do not exceed a darifenacin dosage of 7.5 mg daily1

Nelfinavir

Possible increased plasma darifenacin concentrations1

Do not exceed a darifenacin dosage of 7.5 mg daily1

Paroxetine

Increased plasma darifenacin concentrations1

No dosage adjustment required1

Ritonavir

Possible increased plasma darifenacin concentrations1

Do not exceed a darifenacin dosage of 7.5 mg daily1

Thioridazine

Possible increased thioridazine concentrations1

Use concomitantly with caution1

Verapamil

Possible increased plasma darifenacin concentrations1

No dosage adjustment required1

Warfarin

No substantial effect on PT1

Continue routine monitoring of PT1

Actions

  • Potent and selective antimuscarinic agent.1

  • Inhibits binding of acetylcholine to muscarinic receptors in cholinergically innervated organs.8

  • Demonstrates substantially greater binding affinity for muscarinic M3 receptors (which are involved in contraction of detrusor muscle of bladder and GI smooth muscle, saliva production, and iris sphincter function) in vitro than for other muscarinic receptor subtypes.1 3 8 Exhibits functional selectivity for urinary bladder over secretory (e.g., salivary) glands.2 3

  • Increases bladder capacity and diminishes frequency of unstable contractions of detrusor muscle in patients with involuntary detrusor contractions.1

Advice to Patients

  • Risk of constipation, urinary retention, blurred vision, and heat prostration (when used in a hot environment).1 4 Use caution when driving or performing dangerous activities until effects on vision are known.4

  • Importance of taking tablets with liquids and swallowing whole; do not chew, divide, or crush.1 4 If a dose is skipped, resume therapy the next day; do not take 2 doses in the same day.4

  • Importance of reading manufacturer’s patient information leaflet before initiating therapy.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Uses For Enablex

Darifenacin is used to treat symptoms of an overactive bladder, such as incontinence (loss of bladder control) or a frequent need to urinate. Darifenacin works on the muscles of the bladder to prevent them from causing incontinence.

This medicine is available only with your doctor's prescription.

Overdosage

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.

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.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL - 7.5 mg

N 0430-0170-15

Rx only

Enablex® (darifenacin) Extended-release tablets

7.5 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.

How should I take Enablex?

Take Enablex exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine with water.

Enablex can be taken with or without food.

Do not crush, chew, or break an extended-release tablet. Swallow it whole.

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

(web3)