darifenacin: clinical use

Prescribing considerations

• Exclude or address other causes of urinary frequency, including urinary infection, heart failure and renal disease.
• Assess bladder outflow obstruction, post-void symptoms, bowel function, gastrointestinal motility, glaucoma, hepatic function, cardiac disease and overall anticholinergic burden.
• Safety and efficacy are not established for neurogenic detrusor overactivity or in people under 18.
• Use cautiously in renal impairment.
• Moderate hepatic impairment substantially increases unbound exposure and requires careful benefit–risk assessment.

Contraindications and cautions

• Hypersensitivity to darifenacin or product excipients
• Urinary retention or gastric retention
• Uncontrolled narrow-angle glaucoma
• Myasthenia gravis
• Severe hepatic impairment
• Severe ulcerative colitis or toxic megacolon
• Concurrent potent CYP3A4 inhibition

Monitoring

• Review symptom response and adverse effects, especially constipation, dry mouth, visual disturbance and urinary retention.
• Consider cognitive and neuropsychiatric effects if confusion, altered thinking or hallucinations develop.
• Monitor digoxin concentrations when clinically indicated around changes in darifenacin treatment.
• Reassess promptly if bowel obstruction, worsening bladder emptying or angioedema is suspected.

Clinical pharmacology

Darifenacin is an in-vitro selective M3 muscarinic receptor antagonist. It undergoes extensive first-pass and hepatic metabolism through CYP3A4 and CYP2D6, is highly protein-bound and has active exposure that varies with CYP2D6 phenotype and interacting inhibitors. Its circulating metabolites do not contribute significantly to the clinical effect.

Formulation and product differences

• The product is a film-coated prolonged-release tablet.
• The tablet must remain intact; chewing, dividing or crushing can disrupt prolonged release.
• Food does not materially affect the pharmacokinetics of the prolonged-release formulation.

Modified-release tablet

Route: Oral

Strengths: 7.5 mg, 15 mg