This multinational study randomized 325 men over age 45 with IPSS ≥ 13 to either tadalafil, 5 mg, daily or placebo for 12 weeks. This followed a 4-week wash-out learn more period and 4-week placebo lead-in period. Compared with placebo, tadalafil significantly improved IPSS voiding and storage subscores (P = .02 and .002, respectively). The QoL index also improved (P = .013) but no difference was observed with the nocturia question (P = .233). IPSS questions for frequency (question 2) and urgency (question 3) improved significantly compared with placebo (P < .001 and P = .035, respectively). Tadalafil improved IIEF-EF domain at 12 weeks (least

squares treatment difference [95% CI, 2.5–6.9], Inhibitors,research,lifescience,medical P < .001). Few treatment Inhibitors,research,lifescience,medical emergent adverse events (TEAEs) were reported and the proportion of reporting at least one TEAE was similar between the placebo and treatment groups (tadalafil 26% vs placebo 22%). For tadalafil, most TEAEs were mild to

moderate in severity with the most common being headache (3.7%) and back pain (3.1%). Small increases in Qmax (tadalafil Inhibitors,research,lifescience,medical 1.6 mL/s [4.6] vs placebo 1.1 mL/s [4.6]; P = .30) and in postvoid residual volume (PVR) (tadalafil 8.8 mL [56.4] vs placebo 4.5 mL [66.7]; P = .50) were observed in both treatment groups.27 Several other studies assessing tadalafil administered once daily in men with LUTS and ED have demonstrated significantly improved ED and BPH outcomes with sustained benefits and excellent tolerability.29,30 Based on these randomized, placebo-controlled, double-blind trials, the US Food and Drug Administration (FDA) Inhibitors,research,lifescience,medical approved tadalafil in October 2011 for the treatment of LUTS secondary to BPH, as well as for the treatment of concurrent LUTS and ED. Combination α-Blocker and PDE5-I α1-Adrenergic blockers (α-blockers) are considered the first-line monotherapy for LUTS secondary to BPH. Concerns regarding the coadministration of α-blockers and PDE5-I are related to potential drug-drug interactions leading to hemodynamic Inhibitors,research,lifescience,medical changes and significant lowering of

blood pressure. Kloner and for colleagues assessed the safety of combining tadalafil with two different α-blockers. In the first study, healthy volunteers took doxazosin, 8 mg, for 7 days, followed by coadministration of either tadalafil, 20 mg, or placebo for a single dose. Although there was a greater decrease in mean maximal systolic blood pressure in the doxazosin plus tadalafil group, symptoms of dizziness experienced by three patients did not correlate to measurable changes in blood pressure. The second study had healthy subjects take tamsulosin, 0.4 mg, for 7 days, followed by a single dose of tadalafil (10 or 20 mg) or placebo given 2 hours after the α-blocker. There were no statistically significant differences seen in standing systolic blood pressure between groups.