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INTRODUCTION

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darifenacin (dar-i-fen-a-sin)

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Classification

Therapeutic: urinary tract antispasmodics

Pharmacologic: anticholinergics

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Indications
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Overactive bladder with symptoms (urge incontinence, urgency, frequency).

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Action
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Acts as a muscarinic (cholinergic) receptor antagonist; antagonizes bladder smooth muscle contraction. Therapeutic Effects: Decreased symptoms of overactive bladder.

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Adverse Reactions/Side Effects
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CNS: dizziness. EENT: blurred vision. GI: constipation, dry mouth, dyspepsia, nausea. Metab: heat intolerance.

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PHYSICAL THERAPY IMPLICATIONS

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Examination and Evaluation
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  • Monitor the frequency and urgency of urination to help document whether this drug is successful in controlling overactive bladder.

  • Assess dizziness and blurred vision that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician, and caution the patient and family/caregivers to guard against falls and trauma.

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Interventions
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  • Implement pelvic floor strengthening and other therapeutic exercises to help maintain adequate sphincter control and prevent urine leakage during coughing, sneezing, and so forth.

  • Because of heat intolerance, use care during aerobic exercises. Exercises should be done in a cool environment to prevent hyperthermia.

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Patient/Client-Related Instruction
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  • Instruct patient to report other bothersome side effects such as severe or prolonged nausea, constipation, dry mouth, or indigestion.

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Pharmacokinetics
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Absorption: 15–19% absorbed.

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Distribution: Unknown.

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Protein Binding: 98%.

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Metabolism and Excretion: Extensively metabolized by the CYP2D6 enzyme system in most individuals; poor metabolizers (7% of whites, 2% of African Americans) have less CYP2D6 activity with less metabolism occurring. Some metabolism via CYP3A4 enzyme system. 60% excreted renally as metabolites, 40% in feces as metabolites.

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Half-life: 13–19 hr.

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TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION
PO unknown 7 hr 24 hr

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Contraindications/Precautions
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Contraindicated in: Hypersensitivity; Urinary retention; Gastric retention; Uncontrolled angle-closure glaucoma; Severe hepatic impairment.

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Use Cautiously in: Concurrent use of CYP3A4 inhibitors (use lower dose/clinical monitoring may be necessary); Moderate hepatic impairment (lower dose recommended); Bladder outflow obstruction; GI obstructive disorders, ↓ GI motility, Severe constipation or ulcerative colitis; Myasthenia gravis; Angle-closure glaucoma; Lactation or children (safety not established); Pregnancy (use only if maternal benefit outweighs fetal risk).

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Interactions
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Drug-Drug: Blood levels and risk of toxicity are ↑ by concurrent use of strong CYP3A4 inhibitors, including ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, and nefazodone; daily dose should not exceed 7.5 mg. Concurrent use of moderate inhibitors of CYP3A4, especially those with narrow therapeutic indices, including flecainide, thioridazine, and tricyclic antidepressants should be undertaken with caution.

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Route/Dosage
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PO (Adults): 7.5 ...

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