What is Silodosin (generic name) used for?

Silodosin: Primary Indication and Clinical Use

Silodosin is FDA-approved exclusively for treating the signs and symptoms of benign prostatic hyperplasia (BPH) and is not indicated for hypertension. 1

Mechanism of Action

• Silodosin functions as a highly selective alpha-1A adrenergic receptor antagonist, with 583-fold greater affinity for alpha-1A receptors compared to alpha-1B receptors 2
• This selectivity causes smooth muscle relaxation specifically in the prostate and urethra, decreasing urethral resistance and improving urinary flow rates in BPH patients 3, 4
• The American Urological Association classifies silodosin among the uroselective alpha blockers due to its high alpha-1A receptor selectivity, resulting in fewer cardiovascular side effects while maintaining efficacy for urinary symptoms 3

Clinical Efficacy in BPH

• Patients receiving silodosin 8 mg once daily demonstrated significant improvements in International Prostate Symptom Score (IPSS) and maximum urinary flow rate compared to placebo across three phase III trials 5
• The largest clinical trial showed IPSS reduction of -6.4 points with silodosin versus -3.5 points with placebo (p < 0.0001) 6
• Silodosin improved urinary flow rates by approximately 2.8 mL/sec, comparable to other alpha-1 AR antagonists 6
• Silodosin provides rapid symptom relief, with efficacy demonstrated as early as 1 day after initiation for both voiding and storage symptoms 4, 6

Comparative Effectiveness

• In the European phase III trial, silodosin was at least as effective as tamsulosin 0.4 mg once daily in improving total IPSS 5
• Post hoc analysis demonstrated silodosin was significantly more effective than both placebo and tamsulosin in simultaneously improving nocturia, frequency, and incomplete emptying 5
• The American Urological Association recommends silodosin as an equally effective alternative to other alpha-blockers (alfuzosin, doxazosin, tamsulosin, terazosin) for moderate to severe BPH symptoms 7

Dosing and Administration

• The standard dose is 8 mg once daily 5, 4
• Reduce dose to 4 mg once daily for patients with moderate renal dysfunction 6
• Use is contraindicated in patients with severe renal impairment, severe hepatic impairment, or those taking strong CYP3A4 inhibitors 6

Safety Profile and Adverse Effects

• Abnormal or retrograde ejaculation is the most common adverse effect, occurring in 22-28% of patients, though only 2.8% discontinued treatment due to this effect 2, 4, 8
• The incidence of orthostatic hypotension is very low (<3%), significantly lower than with non-selective alpha blockers 2, 4
• Cardiovascular adverse effects are minimal due to alpha-1A selectivity, which minimizes alpha-1B-mediated blood pressure effects 2, 4
• Long-term extension studies in the United States, Europe, and Asia demonstrated sustained safety and efficacy for up to 1 year 5, 8

Clinical Positioning

• Silodosin is preferred for patients without demonstrable prostatic enlargement, where 5-alpha reductase inhibitor therapy is inappropriate 7
• Silodosin is appropriate for patients requiring rapid symptom relief without concern for long-term disease progression 7
• Consider silodosin for men who cannot tolerate or refuse combination therapy due to sexual side effects or cost considerations 7
• Silodosin has higher rates of ejaculatory dysfunction but lower rates of orthostatic hypotension compared to other alpha-blockers 7

Important Clinical Considerations

• Patients planning cataract surgery should inform their ophthalmologist about silodosin use due to risk of intraoperative floppy iris syndrome, similar to other alpha blockers 7, 9
• Alpha-blockers like silodosin do not affect prostate size and should not be used to reduce prostate volume 9
• For patients with significantly enlarged prostates (volume >30cc, PSA >1.5 ng/mL, or palpable enlargement on DRE), combination therapy with a 5-alpha reductase inhibitor provides superior long-term outcomes 7, 9