What are the alternative treatments to Myrbetriq (mirabegron) for overactive bladder?

Alternative Treatments to Myrbetriq (Mirabegron) for Overactive Bladder

If you need an alternative to mirabegron, antimuscarinic medications (such as solifenacin, tolterodine extended-release, darifenacin, or fesoterodine) are the primary pharmacologic alternatives, with solifenacin having the lowest discontinuation rate due to adverse effects among antimuscarinics and tolterodine having a risk profile similar to placebo. 1

First-Line Treatment: Behavioral Therapies (Must Be Offered First)

Before or alongside any pharmacologic alternative, all patients must receive behavioral interventions, as these are as effective as antimuscarinic medications with minimal adverse effects: 1

• Bladder training for urgency urinary incontinence (strong recommendation, moderate-quality evidence) 1
• Pelvic floor muscle training (PFMT) for stress urinary incontinence or combined with bladder training for mixed incontinence 1
• Weight loss and exercise for obese women (can reduce incontinence episodes by up to 47%) 1, 2
• Fluid management with reduction in fluid intake to decrease frequency and urgency 2

These behavioral therapies should be trialed for 8-12 weeks before judging efficacy. 1

Second-Line Pharmacologic Alternatives

Antimuscarinic Medications (Primary Alternatives)

When mirabegron is not suitable, the following antimuscarinics are evidence-based alternatives:

Solifenacin (5-10 mg daily):

• Associated with the lowest risk for discontinuation due to adverse effects among antimuscarinics 1
• Particularly useful if combination therapy may be needed later (solifenacin 5 mg + mirabegron 25-50 mg has the strongest evidence for combination therapy) 1

Tolterodine extended-release (4 mg daily):

• Has a risk for discontinuation similar to placebo 1
• Better tolerability than immediate-release formulations with comparable efficacy 1, 2

Darifenacin:

• Selective M3 receptor antagonist with lower risk of cognitive effects 2
• Risk for discontinuation similar to placebo 1

Fesoterodine:

• In patients ≥80 years, provides superior efficacy to tolterodine (number-needed-to-benefit of 18 for achieving continence) 2

Oxybutynin:

• Available in oral and transdermal formulations but has the highest risk for discontinuation due to adverse effects 1, 2
• Should be reserved for patients who fail other agents

Critical Safety Considerations for Antimuscarinics

Absolute contraindications (do not prescribe): 1, 2

• Narrow-angle glaucoma (unless cleared by ophthalmologist)
• Impaired gastric emptying
• History of urinary retention

Cognitive risk warning:

• There is evidence of an association between antimuscarinic medications and incident dementia, which may be cumulative and dose-dependent 1
• This risk should be discussed with all patients, particularly elderly patients 1
• Beta-3 agonists are typically preferred before antimuscarinics due to cognitive risk concerns 2

Frail patients require extreme caution:

• Patients with mobility deficits, unexplained weight loss, weakness, or cognitive deficits have a lower therapeutic index with both antimuscarinics and beta-3 agonists 1, 2
• In these patients who cannot tolerate medications, behavioral strategies including prompted voiding and fluid management should be emphasized 1

Algorithm for Switching from Mirabegron

Step 1: Ensure behavioral therapies are optimized (bladder training, PFMT, fluid management, weight loss if applicable) 1, 2

Step 2: Select initial antimuscarinic based on patient profile:

• For elderly or cognitively vulnerable patients: Consider tolterodine ER or darifenacin first due to lower cognitive risk 1, 2
• For patients concerned about dry mouth: Solifenacin has the lowest discontinuation rate 1
• For patients ≥80 years: Fesoterodine may provide superior efficacy 2

Step 3: Trial the selected antimuscarinic for 4-8 weeks to assess efficacy and tolerability 1, 2

Step 4: If first antimuscarinic fails or causes intolerable side effects:

• Switch to a different antimuscarinic rather than abandoning the class entirely 1, 2
• Many patients achieve better symptom control or tolerability with a different agent 1
• Consider dose modification (reducing dose or combining with behavioral techniques) 1

Step 5: If refractory to behavioral therapy plus at least one antimuscarinic trial of adequate duration, consider third-line options 1

Combination Therapy Option

If monotherapy with an antimuscarinic is insufficient, combination therapy with solifenacin 5 mg plus mirabegron 25-50 mg can be considered if mirabegron is tolerated but inadequate alone: 1

• The SYNERGY I/II and BESIDE trials provide the strongest evidence for this specific combination 1, 2
• Combination therapy is statistically superior to either monotherapy for reducing incontinence episodes and micturitions 2
• Adverse events (dry mouth, constipation, dyspepsia) are slightly increased with combination versus monotherapy 1, 2

Third-Line Options (For Refractory Cases)

If behavioral therapy plus pharmacologic therapy fails (defined as 8-12 weeks of behavioral therapy and 4-8 weeks of at least one medication), consider: 1

• Intradetrusor onabotulinumtoxinA injections (patients must be willing to perform clean intermittent self-catheterization if needed) 1
• Peripheral tibial nerve stimulation (PTNS) (requires frequent office visits) 1
• Sacral neuromodulation (SNS) (surgical procedure with durable effects) 1

Common Pitfalls to Avoid

• Do not abandon antimuscarinic therapy after failure of one medication without trying another agent, as patients often respond differently to various antimuscarinics 1, 2
• Do not prescribe antimuscarinics to patients with narrow-angle glaucoma, impaired gastric emptying, or history of urinary retention 1, 2
• Do not fail to discuss cognitive risks when prescribing antimuscarinics, especially in elderly patients 1, 2
• Do not start pharmacotherapy without optimizing behavioral therapies first 1, 2
• Do not use antimuscarinics as monotherapy in elderly men with post-void residual ≥250 mL or maximum flow rate <10 mL/s; these patients require alpha-blocker therapy first for bladder outlet obstruction 2

Nutraceuticals and Supplements

There is currently insufficient evidence to support the use of nutraceuticals, vitamins, supplements, or herbal remedies in the treatment of overactive bladder. 1