Silodosin: A selective α1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia

Background: Silodosin is a new α1-adrenergic receptor antagonist that is selective for the α1A-adrenergic receptor. It was approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).Objective: This article reviews the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of silodosin in adult male patients with BPH.Methods: A search of MEDLINE (1950–October 8, 2009), International Pharmaceutical Abstracts (1970–October 8, 2009), and the Iowa Drug Information Service database (1966–October 8, 2009) was conducted using the terms silodosin, KMD-3213, benign prostatic hyperplasia, and α1-adrenergic receptor antagonist. Reports of research and review articles published in English were identified and evaluated, and the bibliographies of these articles were reviewed for additional relevant publications. A search of the FDA Web site was performed, and abstracts and posters presented at scientific meetings of the American Urological Association were reviewed.Results: By antagonizing α1A-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the LUT. Silodosin has greater affinity for the α1A-adrenergic receptor than for the α1B-adrenergic receptor (by a factor of 583), minimizing the propensity for blood pressure-related adverse effects mediated by α1B blockade. In 3 controlled clinical studies in patients with BPH-related LUTS (1 published; 2 presented in the prescribing information and published in a pooled analysis), patients receiving silodosin at a total daily dose of 8 mg had significant improvements in the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) compared with those receiving placebo (both, P < 0.05). The most commonly reported adverse effect was abnormal or retrograde ejaculation (>22%), and the incidence of orthostatic hypotension was low (<3%).Conclusions: In the small number of clinical trials reviewed, silodosin was associated with significant reductions in IPSS and Qmax compared with placebo. To determine whether silodosin's selectivity for the α1A-adrenergic receptor translates into a clinical advantage relative to other available agents, long-term studies evaluating the comparative efficacy and tolerability of silodosin and other α1-blockers (specifically tamsulosin) are necessary.