Lack of Pharmacodynamic Interaction of Silodosin, a Highly Selective α1a-Adrenoceptor Antagonist, With the Phosphodiesterase-5 Inhibitors Sildenafil and Tadalafil in Healthy Men
Received 31 July 2009; accepted 23 October 2009. published online 18 January 2010.
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.
aBladder Control and Pelvic Pain Center, Alliance Urology Specialists, Greensboro, North Carolina
bClinic Research Department, Watson Laboratories, Inc., Salt Lake City, Utah
Reprint requests: Lawrence A. Hill, Pharm.D., R.Ph., Clinical Research, Watson Laboratories, Inc., Research Park, 577 Chipeta Way, Salt Lake City, UT 84108
ABSTRACT