New Drug Approvals: Silodosin for Benign Prostatic Hyperplasia

Abstract

Objective: To review the pharmacology, pharmacokinetics, clinical trials, and safety of silodosin, a recently approved α1A-adrenergic receptor (AR) antagonist for benign prostatic hyperplasia (BPH). Data Sources: English-only articles obtained from MEDLINE (1966–October 2009) using the search terms silodosin and KMD-3213 were reviewed. In addition, a search of International Pharmaceutical Abstracts (1970–October 2009) was conducted. Study Selection and Data Extraction: Available English-language articles were reviewed, as well as abstracts from available non-English articles. Data Synthesis: Silodosin reduces urinary symptoms associated with BPH in as little as 1 day after initiation. The largest clinical trial conducted to date demonstrated a decrease in International Prostate Symptom Score of –6.4 ± 6.63 points compared to –3.5 ± 5.84 in patients receiving placebo (p < 0.0001). Silodosin also improved urinary flow rates by approximately 2.8 ± 3.44 mL/sec, which is comparable to other α1-AR antagonists. The usual dose of silodosin is 8 mg once daily and should be reduced to 4 mg for patients with moderate renal dysfunction. Use is contra indicated in patients with severe renal and hepatic impairment or taking strong CYP3A4 inhibitors. In clinical trials, the most prevalent adverse effects were ejaculatory disturbances, occurring in approximately 28% of patients, although only 2.8% of patients discontinued treatment due to this adverse effect. Preliminary data suggest that, similar to other third-generation α1A-AR antagonists, silodosin has little potential to cause significant cardiovascular adverse effects such as orthostatic hypotension or syncope. To confirm these findings, long-term studies are still needed, especially in patients taking antihypertensive agents and in those with a history of intolerance to other α1-AR antagonists. Conclusions: Silodosin was approved by the Food and Drug Administration in 2008. Long-term studies demonstrating improvement in clinically Important outcomes of BPH have yet to be published. In addition, pharmacoeconomic analyses would assist in defining its current place in therapy. Until this information is available, silodosin may be best reserved as an alternative to other second- and third-generation α1-AR antagonists.