Silodosin

• Benign Prostatic Hyperplasia (BPH)
• Lower Urinary Tract Symptoms
• Urinary Obstruction

Silodosin is a highly selective alpha-1A adrenergic receptor antagonist used to treat the signs and symptoms of benign prostatic hyperplasia (BPH). Its selectivity for the alpha-1A receptor subtype in the prostate provides effective symptom relief with reduced cardiovascular side effects compared to non-selective alpha blockers.

Mechanism of Action

Silodosin works through targeted receptor blockade in the lower urinary tract:

• Selective alpha-1A blockade: 162 times more selective for alpha-1A vs alpha-1B receptors
• Prostate smooth muscle relaxation: Reduces dynamic obstruction at the bladder neck and prostate
• Improved urine flow: Decreases resistance to urinary outflow
• Minimal vascular effects: Reduced binding to alpha-1B receptors in blood vessels limits orthostatic hypotension

The high alpha-1A selectivity means silodosin can relax prostatic smooth muscle without significantly affecting vascular smooth muscle, reducing dizziness and blood pressure effects.

Available Formulations

Silodosin is available as oral capsules:

• 4 mg capsules
• 8 mg capsules (Rapaflo)

Medical Uses

FDA-Approved Indication:

• Treatment of signs and symptoms of benign prostatic hyperplasia (BPH)

Silodosin improves both obstructive symptoms (weak stream, hesitancy, intermittency) and irritative symptoms (frequency, urgency, nocturia).

Dosing Guidelines

Adults:

• 8 mg once daily with a meal
• Take at the same time each day

Renal Impairment:

• CrCl 30-50 mL/min: 4 mg once daily
• CrCl <30 mL/min: Contraindicated

Hepatic Impairment:

• Mild to moderate (Child-Pugh A or B): No adjustment needed
• Severe (Child-Pugh C): Contraindicated

Important Safety Information

Contraindications:

• Severe renal impairment (CrCl <30 mL/min)
• Severe hepatic impairment (Child-Pugh C)
• Concomitant use with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole, ritonavir)

Warnings and Precautions:

• Orthostatic hypotension: May occur, especially after first dose; use caution in patients on antihypertensives
• Intraoperative Floppy Iris Syndrome (IFIS): Has been observed during cataract surgery; inform ophthalmologist before surgery
• Prostate cancer: Rule out before initiating therapy as BPH and prostate cancer may coexist
• Priapism: Rare; seek immediate medical attention if erection persists >4 hours

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole, ritonavir): Contraindicated due to significantly increased silodosin exposure
• Moderate CYP3A4 inhibitors (diltiazem, erythromycin, verapamil): Use with caution
• P-glycoprotein inhibitors (cyclosporine): May increase silodosin levels
• Other alpha-blockers: Avoid concurrent use due to additive effects
• PDE5 inhibitors (sildenafil, tadalafil, vardenafil): Potential additive hypotensive effect
• Antihypertensives: Monitor for additive blood pressure lowering

Special Populations

• Elderly: No dose adjustment needed; monitor for orthostatic symptoms
• Renal Impairment: 4 mg daily for CrCl 30-50; contraindicated if <30
• Hepatic Impairment: Contraindicated in severe impairment
• Women and Children: Not indicated; silodosin is for adult males only