Generic Name

Solifenacin

Mechanism

Solifenacin is a selective antagonist of the muscarinic M3 receptor. By blocking M3 receptors on detrusor smooth muscle, it reduces involuntary contractions and increases bladder capacity, thereby alleviating urgency, frequency, and urge‑incontinence symptoms.
• Highly selective for M3 over M2/M1 receptors → lower incidence of cardiac side‑effects.
• Reversible binding allows titration based on clinical response.

Pharmacokinetics

Solifenacin (oral tablet) is rapidly absorbed (Tmax ≈ 3 h) with ~80 % bioavailability.
• Distribution: Vd ≈ 7 L/kg; crosses the blood‑brain barrier minimally.
• Metabolism: Primarily hepatic via CYP3A4 and CYP2D6; glucuronide conjugates dominate elimination.
• Excretion: 80 % renal (via glomerular filtration and tubular secretion); 10–15 % fecal.
• Half‑life: ~45 h (steady state reached ~2 weeks).
• Drug interactions: Strong CYP3A4 inhibitors (e.g., ketoconazole) increase plasma levels; CYP3A4 inducers (e.g., rifampin) decrease efficacy.

Indications

• Overactive bladder (OAB) in adults (including urinary urge/incontinence).
• Relief of bladder detrusor overactivity secondary to idiopathic OAB.
• Off‑label: management of benign prostatic hyperplasia (BPH)‑related urinary symptoms in some regions, though not approved in the U.S.

Contraindications

• Pregnancy Category C: use only if benefit outweighs risk.
• Allergy: hypersensitivity to solifenacin or any component.
• Severe hepatic impairment: contraindicated due to increased exposure.
• Renal impairment: dose adjustment required; avoid > 50 % CrCl < 30 mL/min in U.S.
• Cataract or ocular disorders: caution due to potential blurred vision.
• Use with caution in patients on other anticholinergics or MAO‑A inhibitors.

Dosing

• Starting dose: 5 mg orally once daily, preferably in the evening.
• Dose titration: Increase to 10 mg once daily if symptoms persist after 12 weeks.
• Renal adjustment (U.S.):
• CrCl ≥ 50 mL/min: 10 mg once daily.
• CrCl 20–49 mL/min: 5 mg once daily.
• CrCl < 20 mL/min: contraindicated.
• Administration tips: Take with or without food; avoid taking on an empty stomach if nausea occurs.

Adverse Effects

• Common ( 1 %):
• Severe constipation → ileus.
• Ocular toxicity (acute angle‑closure glaucoma).
• Urinary retention → catheterization.
• Rare (< 0.1 %):
• Transient hepatic enzyme elevations.

Monitoring

• Baseline: Renal function (CrCl or eGFR), liver enzymes, bladder capacity assessment if feasible.
• Follow‑up:
• Check for constipation and urinary retention symptoms at 4–6 weeks.
• Adjust dose based on efficacy and tolerability.
• Monitor visual acuity if blurred vision reported.
• Special Populations: Frequent monitoring in geriatric patients due to anticholinergic burden.

Clinical Pearls

• Gradual Dose Escalation: 5 mg → 10 mg after ≥12 weeks helps minimize anticholinergic side‑effects.
• Proactive Constipation Management: Initiate stool softeners or mild laxatives at the first sign of constipation to prevent severe ileus.
• Avoid Concomitant Anticholinergics: Combining with oxybutynin or tolterodine can exaggerate dry‑mouth and ocular issues.
• Use in Renal Disease: Administer 5 mg only; consider therapeutic drug monitoring if CrCl 20–49 mL/min.
• Pregnancy Consideration: If a patient becomes pregnant, consider switching to a non‑selective anticholinergic with better safety data (e.g., tolterodine).

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• *Sources: FDA prescribing information, WHO pharmacopoeia, UpToDate review on OAB treatments.*