Pharmacology Update
Silodosin Capsules (Rapaflo™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliot is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
The FDA has approved a new, highly selective alpha-1 adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia (BPH). Silodosin was developed by Kissei Pharmaceuticals Co., Ltd., in Japan, and will be marketed by Watson Pharmaceuticals Inc, as Rapaflo™.
Indication
Silodosin is indicated for the treatment of symptoms due to BPH.1
Dosage
The recommended starting dose is 8 mg once daily. The dose should be reduced to 4 mg in patients with moderate renal impairment. The drug is not recommended for patients with severe renal or hepatic impairment.1
Potential Advantages
Concomitant use of silodosin and sildenofil (Viagra®) or tadalafil (Cialis®) in healthy subjects did not cause any symptomatic changes in blood pressure, heart rate, or orthostasis.2
Potential Disadvantages
Ejaculatory dysfunction has been associated with silodosin and appears to be more common than with tamsulosin.3 Intraoperative Floppy Iris Syndrome is a complication associated with cataract surgery in patients on alpha-1 adrenergic receptor blockers.1
Comments
Silodosin is a highly selective alpha-1 adrenergic receptor antagonist. It has a higher selectivity for the lower urinary tract than prazosin or tamsulosin.4 Its safety and efficacy were shown in pooled data from two phase 3, 12-week, randomized, double-blind, placebo-controlled studies. Subjects were randomized to silodosin 8 mg/daily (n = 466) or placebo (n = 457). The mean age was 64.6 years, 89.3% were Caucasian, and 3.9% were African American. Mean peak urine flow rates (Qmax) were 8.7-8.9 mL/sec, and the mean International Prostate Symptom Score (IPSS) was 21.3. The primary endpoint was the reduction of IPSS and secondary endpoint was improved peak urine flow rates. At 12 weeks, mean reduction in IPSS was -6.4 for silodosin vs -3.5 for placebo (P < 0.0001). Mean improvements in Qmax were 2.6 mL/sec and 1.5 mL/sec, respectively (P = 0.0007). In addition, the irritative and obstructive subscores of IPSS showed statistically significant reduction relative to placebo. Silodosin (4 mg twice daily) was non-inferior to tamsulosin (0.2 mg daily) and actually showed a greater reduction in IPSS at week 2 in Japanese men.3,4 In an open-label 52-week study, silodosin showed long-lasting benefit as demonstrated by continual reduction in IPSS for 52 weeks.4 Retrograde ejaculation was the most common adverse event. In a comparative trial with tamsulosin, abnormal ejaculation occurred in 22.3% of silodosin patients compared to 1.6% for tamsulosin.3 However, the dose of tamsulosin used in the study was lower than the dose typically used in the United States (0.4 mg). Other adverse events include dizziness, light-headedness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion.1
Clinical Implications
Silodosin is the latest addition to the alpha adrenergic antagonist market for the treatment of symptoms due to BPH. Commonly used agents include terazosin, tamsulosin, doxazosin, and alfuzosin. No one agent has shown superiority in terms of improving symptoms or urinary flow, but they can differ in terms of adverse events profile.5,6 The greater alpha-1a selectivity of silodosin is associated with less blood pressure effect but a higher incidence of abnormal ejaculation including retrograde ejaculation. Current therapies for moderate-to-severe symptoms of BPH include alpha adrenergic antagonists and 5-alpha reductase inhibitors (e.g., finasteride, dutasteride). Recent evidence suggests that a combination of both is more effective than either agent alone in patients with larger prostates and higher PSA levels.6-8
References
1. FDA News. Available at: www.fda.gov/bbs/topics/NEWS/2008/NEW01902.html. Accessed Oct. 17, 2008.
2. Watson Pharmaceuticals. Watson announces positive data for Rapaflo™ (silodosin), its investigational product for BPH, at regional AUA conferences; Sept. 30, 2008. Available at: www.medicalnewstoday.com/articles/123442.php. Accessed Oct. 17, 2008.
3. Kawabe K, et al. 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;98:1019-1024.
4. Yoshida M, et al. Silodosin, a novel selective alpha 1A-adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia. Expert Opin Investig Drugs 2007;16:1955-1965.
5. Djavan B, Marberger M. A meta-analysis on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur Urol 1999; 36:1-13.
6. Update on the American Urological Association Guidelines for the Treatment of Benign Prostatic Hyperplasia. Available at: www.auanet.org/. Accessed Nov. 10, 2008.
7. Roehrborn CG, et al. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol 2008;179:616-621.
8. Siami P, et al. Combination therapy with dutasteride and tamsulosin in men with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT (Combination of Avodart and Tamsulosin) trial rationale and study design. Contemp Clin Trial 2007;28:770-779.
The FDA has approved a new, highly selective alpha-1 adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia (BPH).You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content