Trade Names:Enablex- Tablets, extended-release 7.5 mg- Tablets, extended-release 15 mg
Competitive muscarinic receptor antagonist.
Steady-state plasma levels achieved by day 6 of dosing. Steady-state bioavailability is approximately 15% and 19% for 7.5 and 15 mg dose, respectively. Darifenacin 7.5 mg in extensive metabolizers: AUC is 29.24 ng•h/mL, C max is 2.01 ng/mL, T max is 6.49 h. Darifenacin 7.5 mg in poor metabolizers: AUC is 67.56 ng•h/mL, C max is 4.27 ng/mL, T max is 5.20 h. Darifenacin 15 mg in extensive metabolizers: AUC is 88.90 ng•h/mL, C max is 5.76 ng/mL, T max is 7.61 h. Darifenacin 15 mg in poor metabolizers: AUC is 157.71 ng•h/mL, C max is 9.99 ng/mL, T max is 6.71 h.
Approximately 98% protein bound, primarily to alpha 1 -acid-glycoprotein.
Metabolized by CYP2D6 and CYP3A4. The metabolic products of the hydroxylation and N-dealkylation are unlikely to contribute to the clinical effect. Approximately 7% of white patients and 2% of black patients are poor CYP2D6 metabolizers of the drug, in which case metabolism will be mediated principally by the CYP3A4 isozyme. Individuals with normal CYP2D6 activity are referred to as extensive metabolizers.
Approximately 60% eliminated in the urine, 40% in the feces, and 3% eliminated unchanged. Estimated clearance is 40 L/h and 32 L/h in extensive and poor metabolizers, respectively. Elimination t ½ is about 13 to 19 h. Darifenacin 7.5 mg in extensive metabolizers: t ½ is 12.43 h. Darifenacin 7.5 mg in poor metabolizers: t ½ is 19.95 h. Darifenacin 15 mg in extensive metabolizers: t ½ is 12.05 h. Darifenacin 15 mg in poor metabolizers: t ½ is 7.4 h.
Treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.
Patients with or at risk of urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma; hypersensitivity to any component of the product.
PO Start with 7.5 mg once daily. Based on response, dose may be increased to 15 mg once daily within 2 wk of starting therapy.Moderate Hepatic Impairment or Coadministered Potent CYP3A4 InhibitorAdults
PO A dose greater than 7.5 mg daily is not recommended.
Store tablets at controlled room temperature (59° to 86°F). Protect from light.
Frequency and severity of dry mouth, constipation, blurred vision, and other anticholinergic effects may be increased.Drugs predominantly metabolized by CYP2D6 (eg, flecainide, thioridazine, tricyclic antidepressants)
Use with caution, especially with drugs with a narrow therapeutic index.Potent CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir)
Darifenacin plasma concentrations may be elevated by these agents, increasing the pharmacologic and adverse effects.
None well documented.
Hypertension (at least 1%).
Headache (7%); asthenia (3%); dizziness (2%).
Dry skin, pruritus, rash (at least 1%).
Dry eyes (2%); abnormal vision, pharyngitis, rhinitis (at least 1%).
Dry mouth (35%); constipation (21%); dyspepsia (8%); abdominal pain, nausea (4%); diarrhea (2%); vomiting (at least 1%).
UTI (5%); urinary tract disorder, vaginitis (at least 1%).
Weight gain (at least 1%).
Arthralgia, back pain (at least 1%).
Bronchitis, sinusitis (at least 1%).
Accidental injury, flu-syndrome (3%); pain, peripheral edema (at least 1%).
Identify baseline symptoms (urgency, frequency, incontinence) and monitor patient's response to therapy. Ensure therapy is periodically reviewed to determine if therapy needs to be continued without change, or if a dose change (eg, increase, decrease, discontinuation) is indicated. Monitor patient for GI, GU, OPHTH, CNS, and general body side effects. Discontinue therapy immediately if any of the following occur: severe abdominal pain, sudden eye pain, or urinary retention.
Category C .
Safety and efficacy not established.
Use not recommended in patients with severe hepatic impairment.
Because GI motility may be decreased, use with caution in patients with GI obstructive disorders because of risk of gastric retention and use with caution in patients with severe constipation, ulcerative colitis, and myasthenia gravis.
Use with caution and only if benefits outweigh risks in patients being treated for narrow-angle glaucoma.
Use with caution.
Severe muscarinic effects.
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