The most common adverse effect is loss ofseminal emission. This seems to be caused by silodosin's high selectivity forα1A receptors.[8][11]
Intraoperative floppy iris syndrome occurs in some people taking alpha adrenoreceptor antagonists and may lead to complications during cataract surgery.[5]
Other common adverse effects (in more than 1% of patients) are dizziness,orthostatic hypotension, diarrhea, and clogged nose. Less common (0.1–1%) aretachycardia (fast heartbeat),dry mouth,nausea, skin reactions, anderectile dysfunction. Hypersensitivity reactions occur in fewer than 0.01% of patients. There have been reports about intraoperative floppy iris syndrome duringcataract extractions.[8][7]
Combining silodosin with strong inhibitors of the liver enzymeCYP3A4, such asketoconazole, significantly increases its concentrations in theblood plasma and its area under the curve (area under the curve (AUC)). Less potent CYP3A4 inhibitors such asdiltiazem have a less pronounced effect on this parameters, which is not considered clinically significant. Inhibitors andinducers of the enzymeUGT2B7,alcohol dehydrogenases, andaldehyde dehydrogenases, as well as the transporterP-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 withantihypertensive drugs or withPDE5 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 alpha-1A 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 is highly alpha-1A‐selective (0.25 nM) giving a >100‐fold selectivity window compared to the other adrenoceptors.[12] However, it also demonstrates significant β2‐adrenoceptor affinity (~30 nM).[12]
Silodosin has high affinity for the alpha1A-adrenergic receptor in the prostate, thebladder, and theprostatic urethra. By this mechanism, it relaxes thesmooth muscles in these organs, easing urinary flow and other symptoms of benign prostatic hyperplasia.[4]
The absolutebioavailability after oral intake is 32%. Food has little effect on the area under the curve. When in the bloodstream, 96,6% of the substance are bound to bloodplasma proteins. Its mainmetabolite is silodosinglucuronide, which inhibits the α1A receptor with 1/8 of theaffinity 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 received its first marketing approval in Japan in May 2006,[13][11] under the brand name Urief, which is jointly marketed byKissei Pharmaceutical andDaiichi Sankyo.
Kissei licensed the US, Canadian, and Mexican rights for silodosin toWatson Pharmaceuticals (nowAllergan) in 2004.[14]AbbVie absorbed Allergan in 2019. The FDA andHealth Canada approved silodosin under the brand name Rapaflo in October 2008,[15][16] 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. 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. The men also reported the psychosexual side effect of being strongly dissatisfied by their lack of ejaculation.[11]
^abcdefghijk"Silodyx EPAR".European Medicines Agency (EMA). 10 January 2010. 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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