Darifenacin

Approved Indications:

• Overactive Bladder (OAB):
• Treatment of symptoms of OAB including:
• Urge urinary incontinence
• Urgency
• Increased urinary frequency

Clinically Accepted Off-label Uses:

• May be considered in other forms of urinary urgency or frequency not meeting full OAB criteria, under specialist guidance (limited evidence).

Adults (≥18 years):

• Initial Dose:
• 7.5 mg orally once daily.
• Maintenance Dose:
• May be increased to 15 mg once daily after ≥2 weeks based on patient response and tolerability.
• Maximum Dose:
• 15 mg once daily.

Pediatrics (<18 years):

• Not recommended; safety and efficacy not established.

Elderly (≥65 years):

• No dose adjustment needed; monitor for anticholinergic effects.

Hepatic Impairment:

• Moderate (Child-Pugh B):
• Maximum dose: 7.5 mg once daily.
• Severe (Child-Pugh C):
• Use not recommended.

Renal Impairment:

• No dose adjustment required; use cautiously in severe impairment.

Administration:

• Oral administration; tablets should be swallowed whole with water, not chewed, split, or crushed.
• Can be taken with or without food.

Darifenacin is a selective muscarinic M3 receptor antagonist. It inhibits the binding of acetylcholine at M3 receptors in the bladder detrusor muscle, which are primarily responsible for involuntary bladder contractions. By blocking these receptors, darifenacin reduces detrusor muscle overactivity, leading to increased bladder capacity and reduced urgency, frequency, and urge incontinence. Its selectivity for M3 over M1 and M2 receptors results in fewer central nervous system side effects compared to less selective antimuscarinic agents.

Absorption:

• Extended-release formulation; peak plasma concentrations reached within 7 hours post-dose.
• Absolute bioavailability: ~15% (7.5 mg) to 19% (15 mg).

Distribution:

• Volume of distribution: ~163 L.
• Plasma protein binding: ~98%.

Metabolism:

• Extensively metabolized in the liver, primarily via CYP2D6 and CYP3A4 isoenzymes.

Elimination:

• Elimination half-life: ~13 to 19 hours (dose-dependent).
• Excreted primarily in feces (60–70%) and urine (~14–23%) as metabolites.

• Pregnancy:
• FDA Pregnancy Category C. No adequate human studies; use only if benefits justify potential risks. Animal studies showed adverse fetal effects at high doses.
• Lactation:
• Unknown whether darifenacin is excreted in human milk. Due to potential for serious adverse reactions in nursing infants, either discontinue nursing or the drug.

• Primary Class: Anticholinergic
• Subclass: M3-selective muscarinic receptor antagonist

• Known hypersensitivity to darifenacin or any component of the formulation
• Urinary retention
• Gastric retention or severe decreased gastrointestinal motility (e.g., paralytic ileus)
• Uncontrolled narrow-angle glaucoma

• CNS Effects: May cause confusion, hallucinations, or drowsiness, especially in elderly.
• Constipation: May worsen pre-existing constipation; monitor bowel function.
• Urinary Retention: Use cautiously in patients with bladder outlet obstruction.
• Hepatic Impairment: Dose limitations apply.
• QT Prolongation: Potential risk, especially in patients taking other QT-prolonging agents.
• Dry Mouth: Common and dose-dependent; may affect dental health with prolonged use.
• Heat Prostration: Anticholinergic effects may reduce sweating; caution in hot environments.

Common:

• Dry mouth
• Constipation
• Dyspepsia
• Nausea
• Headache
• Blurred vision

Less Common:

• Urinary retention
• Dizziness
• Abdominal pain
• Flatulence
• Fatigue

Serious/Rare:

• Hallucinations, confusion (especially in elderly)
• Severe constipation or bowel obstruction
• QT prolongation and arrhythmias (rare)

• CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole): Increase darifenacin levels; use lower dose (7.5 mg daily) when used together.
• CYP2D6 Inhibitors (e.g., paroxetine, fluoxetine): May increase exposure.
• Anticholinergic Agents: Additive anticholinergic effects may occur; avoid combinations when possible.
• QT-prolonging drugs (e.g., certain antiarrhythmics): Caution advised due to potential additive effect.

• Updated prescribing guidance recommends caution in elderly patients due to anticholinergic burden.
• Darifenacin remains a recommended second-line agent in OAB management per international urology and gynecology guidelines, especially in patients intolerant to less selective agents.

• Store at 20°C to 25°C (68°F to 77°F).
• Excursions permitted to 15°C–30°C (59°F–86°F).
• Protect from moisture and heat.
• Keep in original container; do not crush or split tablets.
• Keep out of reach of children.