Silodosin and Naftopidil: Comparative Tiredness Profile
Silodosin and naftopidil appear to cause similar rates of tiredness and fatigue, with no clinically meaningful difference between the two medications. Both are alpha-1 adrenergic receptor blockers used for benign prostatic hyperplasia, and neither is associated with significant fatigue as a primary adverse effect.
Direct Comparison Evidence
The most relevant evidence comes from a systematic review comparing silodosin directly to naftopidil in men with benign prostatic hyperplasia 1. This analysis included 5 studies with 763 randomized participants and found:
- No significant difference in treatment withdrawal rates between silodosin and naftopidil (RR 1.25,95% CI 0.81 to 1.93), suggesting similar overall tolerability including fatigue-related discontinuations 1
- Cardiovascular adverse events were comparable between the two drugs (RR 1.02,95% CI 0.41 to 2.56), indicating similar rates of dizziness and orthostatic symptoms that could contribute to tiredness 1
Individual Drug Profiles
Silodosin's Fatigue Profile
Silodosin is highly selective for the α1A-adrenergic receptor (583-fold selectivity over α1B), which minimizes blood pressure-related adverse effects that could manifest as tiredness 2, 3. The most commonly reported adverse effects with silodosin are:
- Abnormal/retrograde ejaculation (>22%) - the predominant side effect 2
- Orthostatic hypotension (<3%) - very low incidence 2
- Dizziness and headache - reported but not at high rates 3
Importantly, fatigue is not listed among the common adverse effects of silodosin in clinical trials 2, 4. The drug's high α1A selectivity specifically reduces cardiovascular effects mediated by α1B blockade, which would otherwise contribute to tiredness through blood pressure changes 3.
Naftopidil's Fatigue Profile
While the provided evidence does not contain detailed standalone data on naftopidil's fatigue profile, the direct comparison studies show it performs similarly to silodosin in terms of overall tolerability and cardiovascular effects 1.
Clinical Implications
Neither silodosin nor naftopidil should be selected or avoided based on tiredness concerns, as both demonstrate:
- Low rates of cardiovascular adverse events that could cause fatigue 1
- Similar treatment discontinuation rates suggesting comparable overall tolerability 1
- No evidence of fatigue as a prominent adverse effect in clinical trials 2, 1, 4
Key Differentiating Factor
The primary difference between these medications is sexual adverse events, where silodosin causes significantly more ejaculatory dysfunction (RR 5.93,95% CI 2.16 to 16.29), resulting in 74 more sexual adverse events per 1000 men compared to naftopidil 1. This should be the primary consideration when choosing between these agents, not tiredness.
Common Pitfalls to Avoid
- Do not confuse dizziness with fatigue: While both drugs can cause mild dizziness from orthostatic effects, this is distinct from systemic tiredness and occurs at low rates with both medications 2, 1
- Do not extrapolate from non-selective alpha-blockers: Older agents like doxazosin and terazosin cause more cardiovascular effects and associated fatigue due to lack of α1A selectivity 3