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

 Indications

Overactive bladder with symptoms (urge incontinence,

urgency, frequency).

Action

Acts as a muscarinic (cholinergic) receptor antagonist;

antagonizes bladder smooth muscle contraction.

Therapeutic Effects: Decreased symptoms of overactive

bladder.

Pharmacokinetics

Absorption: 15–19% absorbed.

Distribution: Unknown.

Protein Binding: 98%.

Metabolism and Excretion: Extensively metabolized

by the CYP2D6 enzyme system in most individuals;

poor metabolizers (7% of Caucasians, 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.

Half-life: 13–19 hr.

TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION

PO unknown 7 hr 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Urinary retention;

Gastric retention; Uncontrolled angle-closure

glaucoma; Severe hepatic impairment.

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,pGI motility, severe constipation or

ulcerative colitis; Myasthenia gravis; Angle-closure

glaucoma; Lactation, Pedi: Safety not established; OB:

Use only if maternal benefit outweighs fetal risk.

Adverse Reactions/Side Effects

CNS: confusion, dizziness, drowsiness, hallucinations,

headache. EENT: blurred vision. GI: constipation, dry

mouth, dyspepsia, nausea.Metab: heat intolerance.

Misc: ANGIOEDEMA.

Interactions

Drug-Drug: Blood levels and risk of toxicity areqby

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.

Route/Dosage

PO (Adults): 7.5 mg once daily, may beqafter 2 wk to

15 mg once daily.

Availability

Extended-release tablets: 7.5 mg, 15 mg. Cost: All

strengths $599.48/90.