Is the combination of mirabegron (Myrbetriq) and solifenacin (Vesicare) appropriate for an older adult with overactive bladder (urge urinary incontinence, urgency, frequency) who has not achieved adequate symptom control with either agent alone, has blood pressure ≤140/90 mmHg, no uncontrolled hypertension, no severe hepatic impairment, no narrow‑angle glaucoma, and no history of urinary retention, and what are the recommended dosing and monitoring?

Combination Mirabegron Plus Solifenacin for Refractory Overactive Bladder

Yes, combination therapy with mirabegron 25–50 mg plus solifenacin 5 mg once daily is appropriate and recommended for this older adult with overactive bladder who has failed monotherapy with either agent alone, given the absence of contraindications. 1

Indication for Combination Therapy

• Combination therapy is specifically indicated for patients who remain symptomatic despite an adequate trial of monotherapy with either an antimuscarinic or a β3-adrenoceptor agonist, supported by Grade B evidence from the European Association of Urology. 1
• The American Urological Association explicitly recommends this combination for patients refractory to monotherapy, emphasizing that combination therapy should not be used as first-line treatment. 1
• This patient meets criteria: persistent "wet" OAB symptoms (urge incontinence, urgency, frequency) despite trials of both mirabegron and solifenacin individually. 1

Recommended Dosing Regimen

Start with mirabegron 25 mg plus solifenacin 5 mg once daily, then increase mirabegron to 50 mg after 4 weeks if tolerated. 1, 2

• The BESIDE trial protocol—which enrolled patients remaining incontinent after solifenacin 5 mg monotherapy—initiated mirabegron at 25 mg and escalated to 50 mg at week 4, demonstrating superior efficacy and good tolerability with this stepwise approach. 2
• Both validated regimens (mirabegron 25 mg + solifenacin 5 mg and mirabegron 50 mg + solifenacin 5 mg) are supported by the European Association of Urology. 3
• The American Urological Association recommends the combination of solifenacin 5 mg with mirabegron 25–50 mg once daily as the standard regimen. 1

Evidence of Superior Efficacy

• Combination therapy demonstrates statistically superior efficacy compared to either monotherapy for reducing incontinence episodes, urgency episodes, micturitions, and nocturia, according to the International Continence Society. 1
• In the BESIDE trial, combination therapy was superior to solifenacin 5 mg for reducing daily incontinence (p=0.001) and daily micturitions (p<0.001), and was noninferior to solifenacin 10 mg for incontinence while superior for micturition frequency (p<0.001). 2
• The 12-month SYNERGY II trial demonstrated sustained, clinically meaningful improvements with mirabegron 50 mg + solifenacin 5 mg versus either monotherapy, with combination therapy statistically superior for both incontinence episodes (vs mirabegron: p<0.001; vs solifenacin: p=0.002) and micturitions (vs mirabegron: p<0.001; vs solifenacin: p=0.004). 4

Safety Profile in Older Adults

• Mirabegron 25 mg is particularly effective and safe in older patients (≥65 years) with multiple comorbidities, as stated by the American Geriatrics Society. 1
• In the SYNERGY II prespecified age-stratified analysis, 34.2% of patients were ≥65 years and 9.4% were ≥75 years; combination therapy was well tolerated across all age groups with efficacy maintained regardless of age. 5
• The BESIDE age-stratified analysis (30.9% aged ≥65 years, 8.9% aged ≥75 years) showed no notable differences in vital signs or treatment-emergent adverse events between age groups, with the largest symptom reductions observed with combination therapy in each age cohort. 6

Monitoring Requirements

Monitor blood pressure periodically, especially during initial treatment and dose escalation, as mirabegron can cause dose-dependent blood pressure increases. 1

• The American Heart Association advises blood pressure monitoring particularly in hypertensive patients and during initial treatment. 1
• This patient's baseline blood pressure ≤140/90 mmHg and absence of uncontrolled hypertension make combination therapy appropriate, but ongoing monitoring remains essential. 1
• Assess post-void residual volume at baseline and periodically, especially given the slightly increased risk of urinary retention with combination therapy compared to monotherapy. 1, 7
• Re-evaluate lower urinary tract symptoms regularly; if worsening voiding symptoms or urinary stream deterioration occurs, discontinue therapy. 3

Adverse Event Profile

• Combination therapy shows slightly increased rates of dry mouth, constipation, and dyspepsia compared to monotherapy, as reported by the American Urological Association. 1
• In SYNERGY II, 47% of patients experienced ≥1 treatment-emergent adverse event overall, with slightly higher frequency in the combination group (49%) versus mirabegron (41%) or solifenacin (44%) monotherapy. 4
• Dry mouth was the most common adverse event: combination 6.1%, solifenacin 5.9%, mirabegron 3.9%. 4
• Urinary retention events occur more frequently with combination therapy, requiring vigilance in monitoring. 1
• Common adverse events (>2%) include hypertension, urinary tract infection, and headache. 1

Contraindications Appropriately Excluded

• This patient has no contraindications: blood pressure controlled (≤140/90 mmHg), no severe hepatic impairment, no narrow-angle glaucoma, and no history of urinary retention. 1, 7
• Mirabegron lacks anticholinergic effects, making it safe in narrow-angle glaucoma (unlike antimuscarinics), but this patient does not have glaucoma regardless. 7
• Solifenacin 5 mg is appropriate given the absence of urinary retention history, though post-void residual monitoring remains prudent. 1

Drug Interaction Considerations

• Co-administration of solifenacin and mirabegron has no noticeable effects on the pharmacokinetics of either drug, allowing safe concurrent use without dose adjustments based on drug interactions. 1
• The FDA label confirms that although no dose adjustment is recommended with solifenacin based on lack of pharmacokinetic interaction, mirabegron should be administered with caution to patients taking muscarinic antagonists because of urinary retention risk. 8
• Mirabegron is a moderate CYP2D6 inhibitor; if this patient takes CYP2D6 substrates (e.g., metoprolol, flecainide, propafenone), appropriate monitoring and dose adjustment may be necessary. 8

Expected Timeline for Efficacy

• Mirabegron 25 mg demonstrates efficacy within 8 weeks, while mirabegron 50 mg shows efficacy within 4 weeks, with sustained benefits throughout treatment. 8
• Reassess symptom response at 4–8 weeks after initiating combination therapy and after dose escalation to mirabegron 50 mg. 1

Common Pitfalls to Avoid

• Do not use combination therapy as first-line treatment; the American Urological Association emphasizes combination therapy only after inadequate response to monotherapy. 1
• Do not skip blood pressure monitoring, even though this patient's baseline is controlled; mirabegron can cause dose-dependent increases. 1
• Do not neglect post-void residual assessment, as combination therapy carries higher urinary retention risk than monotherapy. 1
• Do not abandon combination therapy prematurely; allow 4–8 weeks to assess efficacy before judging treatment failure. 7