What are the recommended medications for relaxing the bladder in patients with overactive bladder symptoms?

Bladder Relaxing Medications for Overactive Bladder

First-Line Treatment: Behavioral Therapy Before Medications

All patients with overactive bladder should receive behavioral therapies as first-line treatment before starting any bladder relaxing medications. 1

• Behavioral treatments (bladder training, pelvic floor muscle exercises, fluid management) are as effective as antimuscarinic medications for reducing symptoms and are risk-free 1
• These interventions significantly reduce incontinence episodes, frequency, nocturia, and improve quality of life 1
• Weight loss of just 8% in obese women reduced urgency incontinence episodes by 42% 1
• A 25% reduction in fluid intake and caffeine reduction both significantly decreased frequency and urgency 1

Second-Line Treatment: Oral Antimuscarinic Medications

When behavioral therapy alone is insufficient, oral antimuscarinic agents should be offered as second-line pharmacologic therapy. 1

Recommended Antimuscarinic Options (Listed Alphabetically, No Hierarchy):

• Darifenacin 1
• Fesoterodine 1
• Oxybutynin 1
• Solifenacin 1, 2
• Tolterodine 1
• Trospium 1

Key Evidence on Antimuscarinic Efficacy:

• No compelling evidence exists for differential efficacy across these antimuscarinic medications 1
• All reduce symptoms but commonly cause non-life-threatening side effects: dry mouth, constipation, dry eyes, blurred vision, dyspepsia, UTI, urinary retention, impaired cognitive function 1
• Patients with more severe baseline symptoms experience greater absolute symptom reductions 1
• Tolterodine demonstrates superior tolerability compared to oxybutynin (particularly less dry mouth: 35-37% vs 61-63%) while maintaining equivalent efficacy 3, 4, 5, 6

Special Consideration for Dry Mouth:

• Transdermal oxybutynin may be offered if dry mouth is a concern with oral antimuscarinics 1

Alternative Second-Line Treatment: β3-Adrenoceptor Agonist

Mirabegron (a β3-adrenoceptor agonist) is an effective alternative second-line option, particularly for patients concerned about antimuscarinic side effects. 1, 7, 8

Mirabegron Dosing and Evidence:

• FDA-approved for adult overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency 8
• Standard dosing: 25-50 mg once daily 7, 8
• Mirabegron 25 mg is particularly appropriate for older patients (≥65 years) with multiple comorbidities 7, 9
• Cardiovascular safety has been established with no significant concerns 9
• Requires blood pressure monitoring, especially during initial treatment and in patients with pre-existing hypertension 7

Advantages Over Antimuscarinics:

• Fewer anticholinergic side effects (no dry mouth, constipation, or cognitive impairment) 10
• Better adherence rates compared to antimuscarinics 1
• Effective in both men and women with overactive bladder 1

Combination Therapy for Refractory Symptoms

For patients with inadequate response to monotherapy, combination therapy with mirabegron plus an antimuscarinic agent (particularly solifenacin) provides superior efficacy. 7, 9

Evidence-Based Combination Regimens:

• Mirabegron 25 mg + solifenacin 5 mg once daily 7
• Mirabegron 50 mg + solifenacin 5 mg once daily 7, 9
• Combination therapy demonstrates superior reduction in urinary incontinence episodes, micturitions, urgency episodes, and nocturia compared to either monotherapy 9
• The SYNERGY and BESIDE trials provide strong evidence for combination therapy efficacy and safety 7

Important Caution:

• Mirabegron should be administered with caution when combined with antimuscarinic medications due to increased risk of urinary retention, especially in patients with bladder outlet obstruction 8

Behavioral Therapy Combined with Medications

Behavioral therapies may be combined with antimuscarinic medications to enhance efficacy. 1

Critical Contraindications and Precautions

Absolute Contraindications for Antimuscarinics:

• Narrow-angle glaucoma (unless approved by treating ophthalmologist) 1
• Patients using solid oral forms of potassium chloride (reduced gastric emptying may increase potassium absorption) 1

Use with Extreme Caution:

• Impaired gastric emptying - obtain gastroenterologist clearance before initiating 1
• History of urinary retention - obtain urologist clearance and measure post-void residual (PVR) before initiating 1
• Men with bladder outlet obstruction - regular re-evaluation of symptoms and PVR required 1, 7

Drug Interactions with Mirabegron:

• Mirabegron is a moderate CYP2D6 inhibitor - increases systemic exposure to metoprolol by 229% and desipramine by 241% 8
• Use caution with narrow therapeutic index CYP2D6 substrates (thioridazine, flecainide, propafenone) - appropriate monitoring and dose adjustment necessary 8
• Digoxin interaction - start with lowest digoxin dose and monitor serum concentrations when initiating combination 8
• Ketoconazole (potent CYP3A4 inhibitor) increases mirabegron exposure by 80% 8

Monitoring During Treatment

For Antimuscarinic Therapy:

• Monitor for urinary retention (especially in at-risk patients) 1
• Assess cognitive function in elderly patients 1
• Evaluate for anticholinergic side effects (dry mouth, constipation, blurred vision) 1

For Mirabegron Therapy:

• Regular blood pressure monitoring, especially initially and in hypertensive patients 7
• Discontinue if worsening voiding symptoms or urinary stream occurs 7
• Monitor post-void residual volume in men with lower urinary tract symptoms 1

Referral to Specialist

Patients refractory to both behavioral and medical therapy should be evaluated by an appropriate specialist (urologist or urogynecologist) if they desire additional therapy. 1

• Third-line treatments (sacral neuromodulation, botulinum toxin injections, percutaneous tibial nerve stimulation) present increasing risks that must be balanced with potential efficacy 1