BACKGROUND

Silodosin is a new alpha(1)-adrenergic receptor antagonist that is selective for the alpha(1A)-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 alpha(1)-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 alpha(1A)-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the LUT. Silodosin has greater affinity for the alpha(1A)-adrenergic receptor than for the alpha(1B)-adrenergic receptor (by a factor of 583), minimizing the propensity for blood pressure-related adverse effects mediated by alpha(1B) 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 (Q(max)) 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 Q(max) compared with placebo. To determine whether silodosin's selectivity for the alpha(1A)-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 alpha(1)-blockers (specifically tamsulosin) are necessary.