What is the interaction between mirabegron (Myrbetriq) and Rapaflo (silodosin) in patients with Benign Prostatic Hyperplasia (BPH)?

Mirabegron (Myrbetriq) and Silodosin (Rapaflo) Interaction in BPH Patients

The combination of mirabegron (Myrbetriq) and silodosin (Rapaflo) is safe and effective for men with BPH who have persistent overactive bladder symptoms, with no clinically significant drug interactions reported between these medications. 1, 2

Safety Profile of Combination Therapy

Mirabegron can be safely combined with alpha-blockers like silodosin in men with BPH who have persistent storage symptoms:

• Clinical evidence shows no significant pharmacokinetic interactions between mirabegron and alpha-blockers 1
• The 2023 European Association of Urology guidelines support this combination for men with persistent overactive bladder symptoms despite alpha-blocker therapy 1
• Van Gelderen et al. specifically demonstrated the absence of clinically relevant cardiovascular interactions when mirabegron is added to established alpha-blocker treatment 1

Efficacy of Combination Therapy

The combination therapy provides superior symptom relief compared to alpha-blocker monotherapy:

• Mirabegron add-on therapy to alpha-blockers significantly reduces:

  • Total IPSS scores (from 19.4 to 16.5, p=0.024) 3
  • Storage symptom scores (from 9.1 to 7.6, p=0.015) 3
  • Overactive bladder symptom scores (from 8.8 to 7.3, p=0.005) 3
  • Urgency episodes (OABSS Q3 from 3.5 to 2.7, p=0.002) 3

• The PLUS study demonstrated that adding mirabegron to tamsulosin (another alpha-blocker similar to silodosin) was statistically superior to tamsulosin plus placebo in:

  • Reducing mean number of micturitions per day (-2.00 vs -1.62) 4
  • Increasing mean volume voided per micturition 4
  • Decreasing urgency episodes per day 4

Dosing Considerations

When initiating combination therapy:

• Start with mirabegron 25 mg once daily 2
• After 4-8 weeks, dose can be increased to 50 mg if needed and tolerated 2
• Continue the established dose of silodosin (Rapaflo) 1, 4

Monitoring and Precautions

While the combination is generally safe, monitor for:

1. Urinary retention: Although uncommon, the PLUS study noted slightly higher rates of urinary retention with mirabegron add-on therapy compared to alpha-blocker alone 4

   • Monitor post-void residual volume, especially in the first few weeks
   • Studies show no clinically meaningful changes in post-void residual volume or maximum urinary flow 4, 3

2. Blood pressure: Regular blood pressure monitoring is recommended, especially in patients with pre-existing hypertension 2

3. Other side effects: Most common side effects of mirabegron include hypertension, nasopharyngitis, and UTI, which differ from the typical anticholinergic side effects 2

Clinical Decision Algorithm

1. For patients with BPH on silodosin with persistent storage symptoms:

   • Confirm adequate alpha-blocker therapy duration (≥8 weeks) 3
   • Verify persistent storage symptoms (OABSS ≥3) 3

2. Add mirabegron if:

   • Patient has no severe uncontrolled hypertension
   • No severe hepatic or renal impairment exists 2

3. Evaluate response after 4-8 weeks:

   • If inadequate response and no side effects, increase mirabegron to 50 mg 2
   • If good response, continue combination therapy

Advantages Over Antimuscarinic Add-on Therapy

Mirabegron offers advantages over antimuscarinic agents (like solifenacin) as add-on therapy to alpha-blockers:

• Lower risk of urinary retention 5, 6
• Better cognitive safety profile, especially important in older men 2
• Fewer discontinuations due to adverse events 6
• Improvements in both storage and voiding symptoms 5

The evidence strongly supports that mirabegron is a safe and effective add-on therapy to silodosin for men with BPH who have persistent overactive bladder symptoms, with no significant drug interactions between these medications.