What alternative treatment options are available for an elderly patient with overactive bladder and a history of cardiac disorders, currently on mirabegron (Myrbetriq) 25mg, who had to discontinue solifenacin and oxybutynin due to side effects?

Management of Persistent Overactive Bladder Symptoms in an Elderly Cardiac Patient

For this elderly patient with cardiac comorbidities who has failed antimuscarinics and has inadequate response to mirabegron 25mg, the optimal next step is to increase mirabegron to 50mg once daily, as this dose demonstrates superior efficacy with similar tolerability, and if symptoms persist, consider adding solifenacin 5mg to create combination therapy. 1, 2

Optimizing Current Beta-3 Agonist Therapy

Dose Escalation Strategy

• Mirabegron 50mg once daily is significantly more effective than 25mg for reducing incontinence episodes, micturition frequency, and urgency episodes in overactive bladder 1
• The 50mg dose achieved statistically significant improvements within 4 weeks compared to 8 weeks for the 25mg dose, with efficacy maintained through 12 weeks of treatment 1
• In clinical trials, mirabegron 50mg reduced incontinence episodes by 1.38-1.57 episodes per 24 hours compared to 0.96-1.17 with placebo, and reduced micturition frequency by 1.60-1.93 episodes per 24 hours 1

Safety Profile in Cardiac Patients

• Mirabegron's most common adverse effects are nasopharyngitis and gastrointestinal disorders, notably avoiding the anticholinergic burden problematic in elderly cardiac patients 3
• Unlike antimuscarinics, mirabegron does not cause dry mouth, constipation, or cognitive impairment that are particularly concerning in elderly patients with polypharmacy 3

Combination Therapy as Second-Line Option

Adding Low-Dose Antimuscarinic

• If mirabegron 50mg alone provides insufficient symptom control, combination therapy with solifenacin 5mg plus mirabegron 25-50mg significantly improves efficacy over monotherapy 2
• Combination therapy improved mean volume voided per micturition by 18.0-26.3 mL compared to solifenacin 5mg alone, and reduced urgency episodes by 0.98-1.37 episodes per 24 hours 2
• The combination was well tolerated with no important additional safety findings compared to monotherapy, though constipation incidence was slightly increased 2

Rationale for Solifenacin Selection

• Solifenacin has the lowest risk for discontinuation due to adverse effects among antimuscarinics (NNTH 78, compared to oxybutynin NNTH 16) 3, 4
• Solifenacin 5mg once daily causes significantly less dry mouth than oxybutynin and is equally well tolerated in elderly patients (>65 years) as in younger patients 5, 6
• In this patient who discontinued both solifenacin and oxybutynin previously, reintroducing solifenacin at the lower 5mg dose in combination with mirabegron may be better tolerated than previous monotherapy 2

Alternative Antimuscarinic Options if Combination Needed

Tolterodine as Preferred Alternative

• Tolterodine and darifenacin have discontinuation rates due to adverse effects similar to placebo, making them the best-tolerated antimuscarinics 3, 7
• Tolterodine causes significantly less dry mouth than oxybutynin (RR 0.65) and has fewer overall adverse events 3, 8
• Tolterodine 2mg twice daily should be the first-line antimuscarinic choice if combination therapy is pursued and solifenacin is not tolerated 7, 4

Darifenacin as Second Alternative

• Darifenacin has a favorable tolerability profile with no statistically significant difference in treatment discontinuation rates compared to placebo 3, 7
• Should be considered if both solifenacin and tolterodine combinations are not tolerated 7

Critical Considerations for Elderly Cardiac Patients

Avoiding High-Risk Antimuscarinics

• Oxybutynin should remain permanently discontinued in this patient given the highest risk for adverse effects (NNTH 16) and discontinuation among all antimuscarinics 3, 4
• Fesoterodine has higher withdrawal rates (RR 1.45) and dry mouth risk (RR 1.80) compared to tolterodine, making it less suitable for elderly patients 9

Polypharmacy Concerns

• Patients receiving 7 or more concomitant medications (common in elderly cardiac patients) experience more adverse effects with antimuscarinics 3
• Mirabegron monotherapy at optimized dosing avoids adding to anticholinergic burden, which is particularly important given this patient's cardiac comorbidities and likely polypharmacy 3

Recommended Treatment Algorithm

1. Increase mirabegron from 25mg to 50mg once daily and reassess symptoms at 4 weeks 1

2. If inadequate response at 4-8 weeks, add solifenacin 5mg once daily to create combination therapy 2

3. If solifenacin combination not tolerated, substitute with tolterodine 2mg twice daily in combination with mirabegron 50mg 7, 8

4. If combination therapy fails or is not tolerated, consider darifenacin monotherapy as it has placebo-level discontinuation rates 3, 7

5. Monitor for cardiac effects (blood pressure, pulse rate) and anticholinergic side effects at each dose adjustment, though these are minimal with mirabegron 1