Silodosin

Approved Indication:

• Benign Prostatic Hyperplasia (BPH):
  Silodosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) in adult men, such as urinary frequency, urgency, nocturia, weak stream, hesitancy, and incomplete bladder emptying.

Clinically Accepted Off-label Uses:

• Distal Ureteral Stones (Medical Expulsive Therapy):
  Used off-label to aid the passage of distal ureteral stones by relaxing ureteric smooth muscle.
• Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS):
  Investigated as a supportive treatment in men with non-bacterial chronic prostatitis, due to its smooth muscle relaxation properties.

Adults (Males):

• Standard Dose: 8 mg orally once daily with food.
• Moderate Renal Impairment (CrCl 30–50 mL/min): 4 mg orally once daily with food.
• Severe Renal Impairment (CrCl <30 mL/min): Use not recommended.

Pediatrics:

• Not indicated or recommended for use in children.

Elderly:

• No specific dose adjustment is required; monitor closely for postural hypotension.

Hepatic Impairment:

• Mild to Moderate: No dose adjustment required.
• Severe: Use not recommended due to lack of safety data.

Administration Notes:

• Take with meals to reduce risk of hypotension.
• Swallow capsule whole; do not open, crush, or chew.

Silodosin is a highly selective α1A-adrenoceptor antagonist. It blocks α1A receptors located in the prostate, bladder neck, and prostatic urethra, leading to smooth muscle relaxation. This improves urinary flow and reduces BPH-related symptoms. Its high uroselectivity minimizes systemic vasodilation and lowers the risk of orthostatic hypotension compared to less selective alpha-blockers.

• Absorption: Peak plasma concentrations achieved within 2.5–6 hours when taken with food.
• Bioavailability: Approximately 32%.
• Protein Binding: ~97%, mainly to albumin.
• Metabolism: Extensively metabolized in the liver via UGT2B7, alcohol and aldehyde dehydrogenases; minor CYP3A4 involvement.
• Active Metabolite: KMD-3213G (pharmacologically active).
• Elimination: 55% in feces; 34% in urine.
• Half-life: Approx. 11 hours.

• Pregnancy: Not for use in women. Animal studies show effects on male fertility.
• Lactation: Not applicable.
• Special Warning: Women of childbearing potential should avoid handling crushed capsules due to reproductive toxicity risk.

• Pharmacologic Class: Alpha-1 Adrenergic Receptor Antagonist
• Subclass: Selective α1A-adrenoceptor blocker
• Therapeutic Use: Uroselective agent for BPH symptom relief

• Hypersensitivity to Silodosin or any component of the formulation
• Severe hepatic impairment (Child-Pugh Class C)
• Severe renal impairment (CrCl <30 mL/min)
• Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir)

• Orthostatic Hypotension: Monitor blood pressure, especially during initiation. Risk increases when used with antihypertensives or PDE5 inhibitors.
• Intraoperative Floppy Iris Syndrome (IFIS): Occurs during cataract surgery in patients previously or currently using alpha-blockers.
• Retrograde Ejaculation: Dose-related and reversible after discontinuation.
• Hepatic and Renal Function: Use with caution and monitor regularly in impaired patients.
• Driving & Machinery Use: May cause dizziness or fainting.

Very Common (≥10%):

• Retrograde ejaculation

Common (1%–10%):

• Dizziness
• Orthostatic hypotension
• Diarrhea
• Nasal congestion
• Headache

Uncommon (<1%):

• Syncope
• Rash
• Abdominal discomfort

Rare but Serious:

• Intraoperative Floppy Iris Syndrome
• Severe hypotension
• Hypersensitivity reactions

Major Interactions:

• Strong CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin): Contraindicated due to increased systemic exposure and risk of hypotension.
• PDE5 Inhibitors (e.g., sildenafil, tadalafil): May enhance hypotensive effect; monitor blood pressure.
• Other α-blockers: Avoid concurrent use due to additive effects on blood pressure.

Minor Interactions:

• Limited interactions with warfarin, atenolol, and digoxin.

Food Interactions:

• Must be taken with food to reduce orthostatic hypotension.

• AUA & EAU Guidelines: Silodosin remains recommended as a first-line α-blocker therapy for moderate to severe BPH symptoms, especially in men with low cardiovascular risk.
• Clinical Preference: Increasing use due to superior uroselectivity and lower risk of systemic side effects compared to tamsulosin or alfuzosin.
• No New FDA or EMA Label Changes reported in the past 12 months.

• Temperature: Store at 20–25°C (68–77°F); excursions permitted between 15–30°C (59–86°F).
• Humidity: Store in a dry place; avoid exposure to moisture.
• Light Protection: Store in original container to protect from light.
• Handling: Keep out of reach of children. Do not crush or chew capsules.