Mirabegron Plus Solifenacin: What SYNERGY Found

A second bladder prescription brings a practical question: what would it add to the medicine you already take? Write down the name, dose, start date and changes you have noticed before the appointment. Ask the prescriber to compare the proposed combination with continuing your current treatment.

Who entered the trial

SYNERGY randomized 3,527 adults with leaking overactive bladder for 12 weeks. Analysis included 3,308; exclusions included 96 treated participants from one noncompliant site. Stress-only leakage was not studied. Coprimary outcomes were daily leaks and voids.¹

What the extra reduction meant

Solifenacin 5 mg plus mirabegron 50 mg reduced leaks by an additional 0.23 per day versus mirabegron 50 mg: 95% confidence interval −0.47 to +0.01; P=.052. Superiority was not established. Failure of this first coprimary comparison stopped confirmatory testing; subsequent comparisons were nominal, exploratory findings.¹

Ask which comparison supports the proposed second prescription and whether it belonged to the trial’s confirmatory testing.

What happened alongside treatment

Dry mouth: 61/848 on this combination versus 14/422 on mirabegron. Four participants across both combination groups required catheterization. Sponsor Astellas employed several authors. Longer-term safety was not established.¹

Bring constipation, dry mouth or difficulty emptying into the discussion even if you are unsure which medicine is responsible. Record when each symptom started, including whether it preceded the proposed second prescription.

What to settle before adding a prescription

The 2024 US AUA/SUFU² guideline permits adding a medicine from a different class when one medicine provides inadequate improvement. It also calls for discussion of possible dementia and cognitive impairment risk with antimuscarinics.²

The current US Myrbetriq label starts combination treatment at mirabegron 25 mg plus solifenacin 5 mg once daily; mirabegron may increase after four to eight weeks. Kidney or liver impairment can limit dosing. Mirabegron requires periodic blood-pressure checks and is not recommended with severe uncontrolled hypertension, defined as at least 180 systolic or 110 diastolic. The label warns about retention with solifenacin and interactions involving CYP2D6 medicines or digoxin.³

Solifenacin is contraindicated with urinary retention, gastric retention or uncontrolled narrow-angle glaucoma. Its label warns about confusion, hallucinations and sleepiness, and advises against use in people at high risk of QT prolongation.⁴ Seek medical help promptly if you cannot urinate. Ask the pharmacist to review the complete medication list, including nonprescription products. Ask the prescriber which symptoms should trigger a call and when benefit and side effects will be reassessed.

For the two beta-3 medicines considered individually, see our mirabegron and vibegron questions.

Laugh, Sneeze, Jump, in “What to Say in the Room,” suggests bringing an earlier three-day bladder record, a recent one and a complete medicine list. Use those pages to prepare the comparison for your visit. See the book.