Lack of Pharmacodynamic Interaction of Silodosin, a Highly Selective α1a-Adrenoceptor Antagonist, With the Phosphodiesterase-5 Inhibitors Sildenafil and Tadalafil in Healthy Men

Objectives

To evaluate the orthostatic effects and safety of coadministration of silodosin with the phosphodiesterase-5 inhibitors sildenafil and tadalafil.

Methods

In this placebo-controlled, open-label crossover study, 22 healthy men aged 45-78 years received 8 mg silodosin for 21 days. On days 7, 14, and 21, subjects also received a single dose of sildenafil 100 mg, tadalafil 20 mg, or placebo in random sequence. Orthostatic tests were performed before (baseline) and 1-12 hours after single-dose treatment. A positive orthostatic test was defined as decrease in systolic blood pressure (SBP) >30 mm Hg, decrease in diastolic blood pressure (DBP) >20 mm Hg, increase in heart rate (HR) >20 bpm, or presence of orthostatic symptoms. Treatment effects were compared by analysis of covariance.

Results

In comparison with placebo, sildenafil or tadalafil caused small but statistically significant reductions in blood pressure; however, no statistically significant orthostatic changes in SBP, DBP, or HR (P >.05) were caused. Time-matched maximum mean difference (95% confidence interval) vs placebo in 1-minute orthostatic change was −2.3 (−6.8-2.2) mm Hg for SBP, −2.2 (−5.6-1.2) mm Hg for DBP, and 1.7 (−1.5-4.9) bpm for HR. The number of postdose positive orthostatic tests was similar for all treatments (sildenafil, 57; tadalafil, 59; placebo, 53). Adverse events (in 7 subjects) were mild (26) or moderate (2). No orthostatic symptoms occurred.

Conclusions

Coadministration of silodosin and maximum therapeutic doses of sildenafil or tadalafil in healthy men caused no clinically important orthostatic changes in blood pressure or HR and no orthostatic symptoms.