What is solifenacin?

What is Solifenacin

Solifenacin is a competitive muscarinic receptor antagonist (specifically targeting M1 and M3 receptors) used primarily as second-line therapy for overactive bladder syndrome after behavioral therapies have failed. 1, 2

Mechanism of Action

• Solifenacin works by blocking muscarinic receptors that mediate contractions of urinary bladder smooth muscle, thereby reducing bladder overactivity 2
• The drug demonstrates bladder selectivity over salivary glands, which theoretically reduces anticholinergic side effects compared to some other agents 3

Clinical Indications

Primary Use: Overactive Bladder

• Solifenacin is FDA-approved for treating overactive bladder symptoms in adults, including urge urinary incontinence, urgency, and urinary frequency 2
• The American Urological Association recommends it as second-line therapy after behavioral interventions 1
• It demonstrates efficacy for all overactive bladder symptoms: reduction in incontinence episodes, urgency episodes, urinary frequency, nocturia, and improvement in functional bladder capacity 1, 4

Combination Therapy Applications

• For men with both storage and voiding lower urinary tract symptoms, solifenacin can be combined with tamsulosin (an alpha-blocker) 5
• The European Association of Urology recommends combination therapy with solifenacin plus mirabegron 50 mg, which demonstrates superior efficacy to either medication alone 1
• Solifenacin should NOT be used as monotherapy for benign prostatic hyperplasia (BPH), as it has minimal effect on voiding symptoms 6

Dosing and Administration

• Available in 5 mg and 10 mg oral tablets 2
• Administered once daily with or without food 2
• The absolute bioavailability is approximately 90%, and food does not significantly affect absorption 2, 7
• Therapeutic effects typically occur after 2-4 weeks of treatment 7

Pharmacokinetics

• Peak plasma concentrations reached 3-8 hours after administration 2, 7
• Highly protein bound (98%) 2
• Metabolized primarily via CYP3A4 in the liver 2, 7
• Terminal elimination half-life of 33-85 hours, permitting once-daily dosing 7
• Only 7% excreted unchanged in urine 7

Critical Safety Considerations and Contraindications

Absolute Contraindications

• Do not use in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma 2
• Contraindicated in patients with known hypersensitivity to solifenacin 2

Use with Extreme Caution

• Patients with impaired gastric emptying, history of urinary retention, or narrow-angle glaucoma require extreme caution per the American Urological Association 1
• Bladder outlet obstruction increases risk of urinary retention 2
• Conditions associated with decreased gastrointestinal motility 2

Dose Adjustments Required

• Limit to 5 mg daily maximum in patients with moderate hepatic impairment (Child-Pugh 7-9) 7
• Limit to 5 mg daily maximum in patients with severe renal impairment (creatinine clearance <30 mL/min) 7
• Limit to 5 mg daily maximum when co-administered with potent CYP3A4 inhibitors (e.g., ketoconazole), as exposure increases approximately 2-fold 7

Common Adverse Effects

• Dry mouth: 10.9% (5 mg dose) to 27.1% (10 mg dose) 8
• Constipation: 5.3% (5 mg dose) to 17.1% (10 mg dose) 8
• Blurred vision: approximately 4.5-4.7% 8
• Decreased sweating leading to potential heat prostration in hot environments 2
• Central nervous system effects including drowsiness 2

Serious Adverse Effects

• Angioedema (edema of tongue, laryngopharynx, or difficulty breathing) requires immediate discontinuation and emergency care 2
• Urinary retention, particularly in patients with bladder outlet obstruction 2
• QT interval prolongation at supratherapeutic doses (30 mg showed 8 msec increase) 2

Clinical Efficacy Data

• In Phase III trials, solifenacin 10 mg reduced micturitions per 24 hours by 3.0 episodes versus 1.5 with placebo (P<0.001) 8
• Incontinence episodes decreased by 2.0 versus 1.1 with placebo (P<0.001) 8
• 52.9% of patients with baseline incontinence achieved complete continence with solifenacin 10 mg versus 33.8% with placebo 8
• Solifenacin 5 mg demonstrated superiority over tolterodine ER 4 mg in reducing incontinence episodes (-1.30 vs -0.90, P=0.018) 7

Important Clinical Pearls

• Patients should be counseled to avoid driving or operating heavy machinery until they know how solifenacin affects them due to potential blurred vision and drowsiness 2
• Advise patients to contact healthcare providers if severe abdominal pain occurs or constipation persists for 3 or more days 2
• The drug is not approved for use in children 2
• Pregnancy category and breastfeeding safety are not well established; discuss risks versus benefits 2