Is dutasteride (Avodart) necessary in combination with silodosin (Rapaflo) for treating benign prostatic hyperplasia (BPH)?

Dutasteride with Silodosin in BPH Treatment

Combination therapy with dutasteride is necessary when using silodosin (Rapaflo) for BPH in patients with prostate enlargement (>30cc), as it provides superior outcomes in reducing the risk of disease progression compared to silodosin monotherapy. 1, 2

Decision Algorithm for Combination Therapy

When to Use Combination Therapy:

• Prostate size >30cc: Patients with enlarged prostates benefit most from combination therapy 2
• Moderate-to-severe LUTS: Combination provides greater symptom improvement than monotherapy 3
• Risk factors for disease progression: Including:
  • Higher PSA levels
  • Older age
  • History of urinary retention
  • Severe symptoms at baseline

When Monotherapy May Be Sufficient:

• Small prostate (<30cc)
• Mild symptoms with minimal bother
• Contraindications to 5-alpha reductase inhibitors

Evidence Supporting Combination Therapy

The CombAT study demonstrated that combination therapy with a 5-alpha reductase inhibitor (dutasteride) and an alpha-blocker (tamsulosin) was significantly superior to either monotherapy alone in:

1. Reducing the risk of acute urinary retention (AUR)
2. Decreasing the need for BPH-related surgery
3. Preventing clinical progression of BPH
4. Providing greater symptom improvement 1, 3

After 4 years of treatment, combination therapy showed:

• 66% reduction in the relative risk of AUR or BPH-related surgery compared to tamsulosin monotherapy
• 19.6% reduction in prostate volume (compared to 1.5% increase with tamsulosin alone) 3

Mechanism of Action and Complementary Effects

The two medications work through different mechanisms:

• Silodosin (Rapaflo): Alpha-1A adrenergic receptor antagonist that relaxes smooth muscle in the prostate and bladder neck, providing rapid symptom relief 1, 2
• Dutasteride (Avodart): Dual 5-alpha reductase inhibitor that reduces DHT levels by approximately 95%, decreasing prostate size over time 2, 4

This complementary approach addresses both the dynamic (muscle tone) and static (prostate enlargement) components of BPH.

Clinical Benefits of Adding Dutasteride

1. Disease Modification: Unlike alpha-blockers alone, dutasteride actually alters the natural history of BPH by reducing prostate volume by up to 26% after 4 years 4

2. Prevention of Complications: Combination therapy reduces the risk of:

   • Acute urinary retention by 67%
   • Need for BPH-related surgery by 64% 2

3. Long-term Efficacy: Combination therapy provides sustained symptom improvement over monotherapy beyond 4 years 3

4. Specific Efficacy in Acute Urinary Retention: In patients with AUR, combination of silodosin and dutasteride achieved 88.8% catheter-free status at 12 weeks 5

Important Considerations and Monitoring

• PSA Monitoring: Dutasteride reduces PSA levels by approximately 50% after 6 months; PSA values should be doubled for comparison to normal ranges 2

• Side Effects: Be aware of potential sexual side effects (reduced libido, erectile dysfunction, ejaculation disorders) and gynecomastia (2.2%) with dutasteride 2

• Follow-up: Schedule follow-up in 3-6 months to assess:

  • Symptom improvement (IPSS score)
  • Medication adherence and side effects
  • Uroflowmetry and post-void residual volume 2

• Intraoperative Considerations: Alert patients to inform ophthalmologists about alpha-blocker use before cataract surgery due to risk of intraoperative floppy iris syndrome 1, 2

Conclusion

For patients with enlarged prostates (>30cc) and moderate-to-severe LUTS, the addition of dutasteride to silodosin therapy provides superior outcomes in terms of symptom improvement, reduction in prostate volume, and prevention of disease progression compared to silodosin monotherapy alone. The combination addresses both the dynamic and static components of BPH, providing both immediate symptom relief and long-term disease modification.