Approved October 8, 2008

SILODOSIN
(FDA Category 1S)

RAPAFLO(R) (Watson Pharmaceuticals, Inc) a selective antagonist of post-synaptic alpha-1 adrenoreceptors, increases smooth muscle relaxation in tissues (prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra), resulting in an improvement in urine flow and a reduction in benign prostatic hyperplasia (BPH).

DOSING INFORMATION: The recommended dose is 8 milligrams orally once daily with a meal.

PHARMACOKINETICS: Following oral administration, the Cmax (61.6 ng/mL) occurs at approximately 2.6 hours. The absolute bioavailability is approximately 32% with a variable effect from food. The drug is approximately 97% bound to plasma proteins with a volume of distribution of approximately 49.5 L. The metabolism occurs primarily through glucuronidation, alcohol and aldehyde dehydrogenase, and CYP3A4 pathways, forming 2 major metabolites (KMD-3213G and KMD-3293). Approximately 33.5% of the drug is eliminated in the urine and 54.9% in the feces. The terminal half-life is approximately 13.3 hours with the metabolite KMD-3213G having an extended half-life of 24 hours.

CAUTIONS: Contraindicated in severe renal impairment (CrCl less than 30 mL/min), severe hepatic impairment (Child-Pugh score 10 or greater), and when given concurrently with strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, itraconazole, ritonavir). Common adverse events include retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion.

FDA APPROVED INDICATIONS: Silodosin is indicated for the treatment of signs and symptoms of benign prostatic hyperplasia (BPH); not indicated for hypertension.