Introduction
Silodosin is a selective alpha-1 adrenergic receptor antagonist specifically developed for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Marketed under the brand name Rapaflo®, it was approved by the FDA in 2008 and represents a uroselective agent with preferential activity on alpha-1A receptors located in the prostate, bladder neck, and urethra.
Mechanism of Action
Silodosin exerts its therapeutic effects through highly selective blockade of postsynaptic alpha-1A adrenergic receptors. These receptors are predominantly located in the smooth muscle of the prostate gland, prostatic capsule, and bladder neck. By antagonizing these receptors, silodosin causes relaxation of smooth muscle in these tissues, resulting in reduced dynamic component of bladder outlet obstruction. This leads to decreased urinary resistance and improved urinary flow without significantly affecting blood pressure, owing to its minimal activity on vascular alpha-1B receptors.
Indications
- Treatment of signs and symptoms of benign prostatic hyperplasia (BPH)
- Improvement of urinary flow rates in patients with BPH
- Reduction of International Prostate Symptom Score (IPSS) in BPH patients
Dosage and Administration
Standard adult dosage: 8 mg orally once daily with a meal Administration: Should be taken with the same meal each day to ensure consistent absorption Renal impairment:- Mild to moderate impairment (CrCl 30-89 mL/min): No dosage adjustment necessary
- Severe impairment (CrCl <30 mL/min): Contraindicated
Pharmacokinetics
Absorption: Rapidly absorbed with Tmax of 2.6-2.9 hours. Bioavailability is approximately 32% when administered with food. Distribution: Volume of distribution is approximately 49.5 L. Protein binding is 97%, primarily to alpha-1 acid glycoprotein. Metabolism: Extensively metabolized via glucuronidation, alcohol dehydrogenase, and CYP3A4-mediated oxidation. The major metabolites are silodosin glucuronide (inactive) and KMD-3213G (active). Elimination: Half-life is approximately 13.3 hours. Excretion is primarily via urine (55%) and feces (34%).Contraindications
- Severe renal impairment (CrCl <30 mL/min)
- Hypersensitivity to silodosin or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors
- Patients with severe hepatic impairment
Warnings and Precautions
Orthostatic hypotension: May cause syncope and orthostatic hypotension, particularly with initial dosing or dosage increases. Patients should be cautioned about driving or operating machinery. Intraoperative floppy iris syndrome: Has been reported during cataract surgery in patients taking alpha-blockers. Ophthalmologists should be informed of silodosin use prior to surgery. Priapism: Rare cases of priapism have been reported. Patients should seek immediate medical attention for prolonged erections. Sulfa allergy: Although not a sulfonamide, use with caution in patients with sulfa allergy due to potential cross-reactivity concerns.Drug Interactions
Strong CYP3A4 inhibitors: (ketoconazole, clarithromycin, ritonavir) - Contraindicated due to significant increase in silodosin exposure Moderate CYP3A4 inhibitors: (erythromycin, diltiazem) - Use with caution and consider dosage reduction Alpha-adrenergic blockers: (tamsulosin, doxazosin) - Avoid concomitant use due to additive effects Phosphodiesterase-5 inhibitors: (sildenafil, tadalafil) - May potentiate hypotensive effects Antihypertensive agents: Enhanced hypotensive effects may occurAdverse Effects
Common (≥2%):- Retrograde ejaculation (28%)
- Dizziness (3.4%)
- Diarrhea (3.2%)
- Orthostatic hypotension (2.9%)
- Nasal congestion (2.2%)
- Headache (1.8%)
- Insomnia
- Increased ALT
- Syncope
- Palpitations
- Priapism (rare)
Monitoring Parameters
- Blood pressure (particularly orthostatic measurements)
- Renal function (baseline and periodically)
- Liver function tests (baseline)
- International Prostate Symptom Score (IPSS)
- Urinary flow rates
- Adverse effects, particularly related to ejaculation and dizziness
Patient Education
- Take medication with the same meal each day to ensure consistent effects
- Rise slowly from sitting or lying positions to minimize dizziness
- Be aware of possible retrograde ejaculation (dry orgasm), which is not harmful but may be concerning
- Inform all healthcare providers, especially ophthalmologists, about silodosin use before any surgery
- Do not crush or break capsules
- Report any episodes of dizziness, fainting, or prolonged erection immediately
- Allow 2-4 weeks for full therapeutic effect
- Do not discontinue abruptly without consulting healthcare provider
References
1. Chapple CR, Montorsi F, Tammela TL, et al. Silodosin therapy for lower urinary tract symptoms in men with suspected benign prostatic hyperplasia: results of an international, randomized, double-blind, placebo- and active-controlled clinical trial performed in Europe. Eur Urol. 2011;59(3):342-352. 2. Marks LS, Gittelman MC, Hill LA, Volinn W, Hoel G. Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonist silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol. 2009;181(6):2634-2640. 3. Rapaflo® (silodosin) capsules prescribing information. Allergan USA, Inc.; 2021. 4. Kawabe K, Yoshida M, Homma Y. Silodosin, a new alpha1A-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int. 2006;98(5):1019-1024. 5. Novara G, Galfano A, Ficarra V, et al. Alpha-blockers for benign prostatic hyperplasia: the new era. Curr Opin Urol. 2012;22(1):7-15.