PROFILE OF SILODOSIN
- Authors: Montorsi F.1
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Affiliations:
- Issue: No 2 (2013)
- Pages: 112-117
- Section: Articles
- URL: https://journals.eco-vector.com/1728-2985/article/view/279757
- ID: 279757
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Abstract
Silodosin is a highly selective a1A-adrenoceptor antagonist approved for the treatment of the signs and symptoms of benign prostatic hyperplasia. Its clinical pharmacology profile offers a number of advantages, including uroselectivity, once-daily (QD) dosing, a standard dose of 8 mg QD that does not need to be adjusted according to age, and the feasibility of concomitant treatment with phosphodiesterase type 5 (PDE5) inhibitors and antihypertensive agents. Three phase 3 double-blind, randomised trials using the dosage regimen of 8 mg QD in >800 patients have shown that silodosin is significantly more effective than placebo ( p < 0.001) and at least as effective as tamsulosin (0.4 mg QD) in improving International Prostate Symptom Score (IPSS) total score, storage subscore, and voiding subscore. It is significantly more effective than tamsulosin in inducing simultaneous improvement of bothersome lower urinary tract symptoms such as incomplete emptying, frequency, and nocturia ( p = 0.03). Safety data collected in 1581 patients exposed to chronic treatment with silodosin 8 mg QD have shown that the drug is safe and well tolerated. As was to be expected with a uroselective compound, cardiovascular effects have been minimal. The most common adverse reaction is “retrograde ejaculation” (anejaculation), which led to treatment discontinuation in only 3.9% of patients. The rare, drug class-related safety issue of intraocular floppy iris syndrome can be satisfactorily managed by warning patients simply to inform their ophthalmologist that they are or were on treatment with an a1-adrenoceptor blocker.
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References
- Unpubl. data, Recordati SpA, Milano, Italy. Summary of Safety (September 2008), Common Technical Documents on fi le, Recordati, Milano, Italy.
- Michel MC, Vrydag W. Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br. J. Pharmacol. 2006; 147: S88-119.
- Roehrborn C.G. Effi cacy of a-adrenergic receptor blockers in the treatment of male lower urinary tract symptoms. Rev. Urol. 2009; 11(Suppl 1): S1-8.
- Guimaraes S., Moura D. Vascular adrenoceptors: an update. Pharmacol. Rev. 2001;53:319-356.
- Tatemichi S., Kiguchi S., Kobayashi M. et al. Cardiovascular effects of the selective alpha1A-adrenoceptor antagonist silodosin (KMD-3213), a drug for the treatment of voiding dysfunction. Arzneimittelforschung. 2006; 56: 682-687.
- Morganroth J., Lepor H., Hill L.A. et al. Effects of the selective alpha(1A)-adrenoceptor antagonist silodosin on ECGs of healthy men in a randomized, double-blind, placebo- and moxifl oxacin-controlled study. Clin. Pharmacol. Ther. 2010;87:609-613.
- Yoshida M., Homma Y., Kawabe K. Silodosin. A novel selective a1A adrenoceptor selective antagonist for the treatment of benign prostatic hyperplasia. Exp. Opin. Invest. Drugs. 2007;16:1955-1965.
- EPARs for authorised medicinal products for human use: Urorec. European Medicines Agency Web site. http://www.ema.europa.eu/ humandocs/Humans/ EPAR/urorec/urorec.htm.
- Guay D.R.P. Silodosin: an orally active selective a1-adrenoceptor antagonist for benign prostatic hyperplasia. Aging Health 2009; 5: 459-473.
- Matsubara Y., Kanazawa T., Kojima Y. et al. Pharmacokinetics and disposition of silodosin (KMD-3213). Yakugaku Zasshi. 2006;126:237-245.
- Jacobsen S.J., Jacobson D.J., Girman C.J. et al. Natural history of prostatism: risk factors for acute urinary retention. J. Urol. 1997;158:481-487.
- Macdiarmid S.A., Hill L.A., Volinn W. et al. Lack of pharmacodynamic interaction of silodosin, a highly selective alpha1A-adrenoceptor antagonist, with the phosphodiesterase-5 inhibitors sildenafi l and tadalafil in healthy men. Urology. 2010;75:520-525.
- Marks L, Gittelmann MC, Hill LA, Volinn W, Hoel G. Rapid efficacy of the highly selective alpha1A-adrenoceptor antagonists silodosin in men with signs and symptoms of benign prostatic hyperplasia: pooled results of 2 phase 3 studies. J Urol 2009; 181: 2634-2640.
- Chapple C. Eur Urol. In press.
- Marks L., Gittelmann M.C., Hill L.A. et al. Silodosin in the treatment of the signs and symptoms of benign prostatic hyperplasia: a 9-month, open-label extension study. Urology. 2009;74:1318-1324.
- Rosen R., Altwein J., Boyle P. et al. Lower urinary tract symptoms and male sexual dysfunction: the Multinational Survey of the Aging Male (MSAM-7). Eur. Urol. 2003;44:637-649.
- Michel M.C. A1-adrenoceptors and ejaculatory function. Br. J. Pharmacol. 2007;152:289-290.
- Kobayashi K., Masumori N., Hisasue S. et al. Inhibition of seminal emission is the main cause of anejaculation induced by a new highly selective a1A-blocker in normal volunteers. J. Sex. Med. 2008;5:2185-2190.
- Kobayashi K., Masumori N., Kato R. et al. Orgasm is preserved regardless of ejaculatory dysfunction with selective alpha1A-blocker administration. Int. J. Impot. Res. 2009;21:306-310.
- Avisar R., Weinberger D. Intraoperative fl oppy iris syndrome: possible relationship with alpha-1 adrenergic receptor antagonists. IMAJ. 2009;11:42-44.
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