What is silodosin used for in adult males with Benign Prostatic Hyperplasia (BPH)?

What is Silodosin?

Silodosin is a highly selective alpha-1A adrenergic receptor antagonist FDA-approved for treating the signs and symptoms of benign prostatic hyperplasia (BPH) in adult males, working by relaxing smooth muscle in the prostate and urethra to improve urinary flow. 1

Mechanism of Action

• Silodosin antagonizes alpha-1A adrenergic receptors specifically located in the prostate and urethra, causing smooth muscle relaxation in the lower urinary tract 2, 3
• The drug has 583-fold greater affinity for alpha-1A receptors compared to alpha-1B receptors, which minimizes cardiovascular side effects (like orthostatic hypotension) that result from alpha-1B blockade in blood vessels 2, 3

FDA-Approved Dosing

• Standard dose: 8 mg capsule taken orally once daily with a meal 1
• Moderate renal impairment (creatinine clearance 30-50 mL/min): 4 mg capsule once daily with a meal 1
• Severe renal impairment (creatinine clearance <30 mL/min): Contraindicated 1

Clinical Efficacy

• Silodosin produces significant improvements in International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) compared to placebo, with early onset of efficacy for both voiding and storage symptoms 2, 3, 4
• In the European trial, silodosin was at least as effective as tamsulosin 0.4 mg in improving total IPSS 5, 4
• Post-hoc analysis showed silodosin significantly more effective than both placebo and tamsulosin in simultaneously improving the triad of nocturia, frequency, and incomplete emptying 4
• Long-term extension studies demonstrated sustained symptom relief for up to 1 year 6, 7

Role in BPH Treatment Guidelines

• The European Association of Urology recommends silodosin as an alternative alpha-blocker when side effects (particularly ejaculatory dysfunction) are problematic with tamsulosin 8
• Silodosin is NOT associated with intraoperative floppy iris syndrome during cataract surgery, unlike tamsulosin, making it the preferred alpha-blocker for patients planning or who have had cataract surgery 8
• The American Urological Association includes silodosin among first-line alpha-blocker alternatives (along with alfuzosin, doxazosin, and terazosin) that are equally effective for symptom improvement but differ in side effect profiles 9

Adverse Effects Profile

• Retrograde or abnormal ejaculation is the most common adverse effect, occurring in >20% of patients 1, 2, 6
• Cardiovascular adverse effects are minimal: orthostatic hypotension occurs in <3% and dizziness in approximately 3% of patients 2, 6
• Other common adverse effects (≥2% incidence) include diarrhea, headache, nasopharyngitis, and nasal congestion 1
• Discontinuation due to retrograde ejaculation is more common in patients starting silodosin de novo (7.5%) compared to those continuing treatment (1.9%) 6

Contraindications

• Severe renal impairment (creatinine clearance <30 mL/min) 1
• Severe hepatic impairment (Child-Pugh score >10) 1
• Concomitant use with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole, ritonavir) 1
• History of hypersensitivity to silodosin or any ingredients 1

Critical Clinical Considerations

• Patients planning cataract surgery should inform their ophthalmologist about silodosin use, though the risk of intraoperative floppy iris syndrome is lower than with tamsulosin 8, 1
• Silodosin should not be used in combination with other alpha-blockers, as interactions are expected even though they have not been formally studied 1
• Concomitant use with PDE5 inhibitors can potentially cause symptomatic hypotension and requires caution 1
• Co-administration with strong P-glycoprotein inhibitors (like cyclosporine) may increase plasma silodosin concentration and is not recommended 1

When to Choose Silodosin Over Other Alpha-Blockers

• Select silodosin for patients with planned or prior cataract surgery due to lower risk of intraoperative floppy iris syndrome 8
• Consider silodosin for patients who cannot tolerate tamsulosin's ejaculatory side effects, though silodosin itself has high rates of this adverse effect 8
• Choose silodosin for patients requiring cardiovascular safety, as the highly selective alpha-1A blockade minimizes orthostatic hypotension 2, 3