Solifenacin

Generic Name: Solifenacin succinate
Brand Names: Vesicare, Vesicare LS
Drug Class: Antimuscarinic agent (urinary antispasmodic)
Pharmaceutical Forms:
– Oral tablets (5 mg and 10 mg)
– Oral suspension (1 mg/mL; Vesicare LS)
Route of Administration: Oral
ATC Code: G04BD08
Legal Classification: Prescription-only medication

Solifenacin is used in the treatment of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO). Its once-daily dosing and selectivity for muscarinic M3 receptors make it a preferred agent in both adult and pediatric urinary incontinence management.

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2. Mechanism of Action

Solifenacin functions as a competitive antagonist of muscarinic acetylcholine receptors, with particular selectivity for the M3 subtype. These receptors are located on the smooth muscle of the urinary bladder and are responsible for mediating involuntary detrusor contractions. By inhibiting M3 receptor activity, solifenacin reduces the urgency and frequency of urination and increases bladder capacity.

Pharmacodynamically, solifenacin does not significantly affect other muscarinic subtypes such as M1 or M2, minimizing central nervous system or cardiac side effects. Its long half-life contributes to a stable therapeutic profile with once-daily administration.

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3. Pharmacokinetics

Absorption:

• High oral bioavailability (~90%)

• Peak plasma concentration occurs 3 to 8 hours after ingestion

Distribution:

• Approximately 98% bound to plasma proteins (mostly α-1-acid glycoprotein)

• Volume of distribution is moderate

Metabolism:

• Extensively metabolized in the liver, primarily via cytochrome P450 3A4 (CYP3A4)

• Produces one pharmacologically active metabolite

Elimination:

• Eliminated through renal (major) and fecal (minor) routes

• Terminal elimination half-life ranges from 45 to 68 hours

• Steady-state plasma levels are achieved within one week

Special Populations:

• In renal impairment: reduced clearance; accumulation possible

• In hepatic impairment: metabolism decreases; exposure increases

• In elderly: pharmacokinetics may not differ significantly, but caution is advised due to comorbidities

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4. Indications

Adults (Tablets):

• Treatment of symptoms associated with overactive bladder, including:

  • Urinary urgency

  • Increased urinary frequency

  • Urge incontinence

Pediatric (Suspension):

• Indicated for the treatment of neurogenic detrusor overactivity (NDO) in children aged 2 years and older

• Used to improve bladder compliance and reduce detrusor pressure

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5. Dosage and Administration

Adult Dosing (Tablets):

• Initial dose: 5 mg once daily

• Maintenance: May be increased to 10 mg once daily based on efficacy and tolerability

• Administration: Swallowed whole with water, with or without food

Pediatric Dosing (Oral Suspension):

• Based on body weight

• Typical range: 2 to 5 mL of suspension once daily (1 mg/mL concentration)

• Shake well before use

• Use calibrated dosing device

Renal Impairment:

• In moderate to severe renal dysfunction, do not exceed 5 mg daily

• Monitor for signs of urinary retention

Hepatic Impairment:

• Moderate hepatic impairment: maximum 5 mg once daily

• Severe hepatic impairment: use not recommended

Concomitant CYP3A4 Inhibitors:

• Limit to 5 mg/day if used with strong CYP3A4 inhibitors (e.g., ketoconazole)

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6. Contraindications

• Urinary retention

• Gastric retention or severe gastrointestinal motility disorders

• Uncontrolled narrow-angle glaucoma

• Known hypersensitivity to solifenacin or any component of the formulation

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7. Warnings and Precautions

Urinary Retention:

• Monitor patients with bladder outlet obstruction or those at risk for voiding difficulty

Gastrointestinal Disorders:

• Use with caution in patients with decreased GI motility (e.g., severe constipation, gastroparesis)

CNS Effects:

• Although CNS penetration is low, monitor for confusion or hallucinations in sensitive populations

QT Prolongation Risk:

• Avoid in patients with known congenital long QT syndrome or taking QT-prolonging drugs

Anaphylaxis and Angioedema:

• Rare hypersensitivity reactions may occur

• Discontinue immediately if facial swelling or difficulty breathing develops

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8. Adverse Effects

Very Common (>10%):

• Dry mouth

Common (1–10%):

• Constipation

• Blurred vision

• Dyspepsia

• Urinary tract infections

• Headache

• Dry eyes

• Nasopharyngitis

• Abdominal pain

Uncommon (0.1–1%):

• Fatigue

• Edema

• Palpitations

• Somnolence

• Skin rash

• Increased hepatic enzymes

Rare (<0.1%):

• Urinary retention

• Hallucinations

• Confusional states

• Tachycardia

• QT interval prolongation

Pediatric Adverse Effects (Oral Suspension):

• Increased risk of constipation and urinary retention

• Gastrointestinal disturbances

• Facial flushing

• Behavioral changes in some cases

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9. Drug Interactions

CYP3A4 Inhibitors:

• Potent inhibitors (e.g., itraconazole, ritonavir, clarithromycin) increase solifenacin plasma levels

• Limit dose to 5 mg/day when used concurrently

Other Anticholinergics:

• Additive adverse effects such as dry mouth, blurred vision, constipation, or urinary retention

• Avoid co-administration unless clinically justified

QT-Prolonging Agents:

• Caution when used with drugs that also prolong the QT interval (e.g., amiodarone, haloperidol)

Prokinetic Agents (e.g., metoclopramide):

• Reduced efficacy of prokinetics due to anticholinergic effects

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10. Use in Specific Populations

Geriatrics:

• Increased sensitivity to side effects such as dry mouth and constipation

• Initiate at lower dose and monitor regularly

Renal Impairment:

• Use caution in moderate to severe impairment

• Avoid dose escalation beyond 5 mg/day

Hepatic Impairment:

• In moderate hepatic dysfunction, use 5 mg/day only

• Avoid use in severe hepatic dysfunction

Pregnancy:

• Not recommended unless benefits outweigh risks

• Limited human data available

Lactation:

• Unknown if excreted in human milk

• Consider alternative therapies or avoid breastfeeding

Pediatrics:

• Approved only for NDO in children ≥2 years using oral suspension

• Close monitoring required, especially for urinary retention and bowel function