The most common adverse effect is loss of seminal emission. This seems to be caused by silodosin's high selectivity for α1A receptors.[8][11]
Intra operative floppy iris syndrome occurs in some people taking alpha adrenoreceptor antagonists and may lead to complications during cataract surgery.[5] Intra operative floppy iris syndrome is a condition that makes the iris floppy.[5]
Combining silodosin with strong inhibitors of the liver enzyme CYP3A4, such as ketoconazole, significantly increases its concentrations in the blood plasma and its area under the curve (AUC). Less potent CYP3A4 inhibitors such as diltiazem have a less pronounced effect on this parameters, which is not considered clinically significant. Inhibitors and inducers of the enzyme UGT2B7, alcohol dehydrogenases, and aldehyde dehydrogenases, as well as the transporter P-glycoprotein (P-gp), may also influence silodosin concentrations in the body. Digoxin, which is transported by P-gp, is not affected by silodosin; this means that silodosin does not significantly inhibit or induce P-gp.[8][7]
No relevant interactions with antihypertensive drugs or with PDE5 inhibitors have been found in studies; although combination with other α1-antagonists is not well studied.[8][7]
Silodosin, is an alpha-adrenoreceptor antagonist.[5] It works by blocking receptors called alpha1A adrenoreceptors in the prostate gland, the bladder and the urethra (the tube that leads from the bladder to the outside of the body).[5] When these receptors are activated, they cause the muscles controlling the flow of urine to contract.[5] By blocking these receptors, silodosin allows these muscles to relax, making it easier to pass urine and relieving the symptoms of BPH.[5]
Silodosin has high affinity for the α1A adrenergic receptor in the prostate, the bladder, and the prostatic urethra. By this mechanism it relaxes the smooth muscle in these organs, easing urinary flow and other symptoms of benign prostatic hyperplasia.[4]
The absolute bioavailability after oral intake is 32%. Food has little effect on the AUC. When in the bloodstream, 96,6% of the substance are bound to blood plasma proteins. Its main metabolite is silodosin glucuronide, which inhibits the α1A receptor with 1/8 of the affinity of the parent substance. 91% of the glucuronide are bound to plasma proteins. The enzyme mainly responsible for the formation of the glucuronide is UGT2B7. Other enzymes involved in the metabolism are alcohol dehydrogenases, aldehyde dehydrogenases and CYP3A4.[5][8]
Silodosin is almost completely excreted in the form of metabolites; 33.5% via the urine and 54.9% via the feces. The biological half-life of silodosin is 11 hours on average, and that of the glucuronide is 18 hours or 24 hours. (Sources are contradictory on this.)[8][7]
Silodosin received its first marketing approval in Japan in May 2006,[12][11] under the brand name Urief, which is jointly marketed by Kissei Pharmaceutical and Daiichi Sankyo.
Kissei licensed the US, Canadian, and Mexican rights for silodosin to Watson Pharmaceuticals (now Allergan) in 2004.[13]AbbVie absorbed Allergan in 2019. The FDA and Health Canada approved silodosin under the brand name Rapaflo in October 2008,[14][15] and January 2011,[3] respectively.
Alpha-1 adrenergic receptor antagonists are being investigated as a means to male birth control due to their ability to inhibit ejaculation but not orgasm.[11] While silodosin was completely efficacious in preventing the release of semen in all subjects, 12 out of the 15 participants reported mild discomfort upon orgasm.[11] The men also reported the psychosexual side effect of being strongly dissatisfied by their lack of ejaculation.[11]
^ abcdefghijkl"Silodyx EPAR". European Medicines Agency (EMA). 2010-01-10. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
Kawabe K, Yoshida M, Homma Y (November 2006). "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 International. 98 (5): 1019–24. doi:10.1111/j.1464-410X.2006.06448.x. PMID16945121. S2CID24649263.
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