|Trade names||Urief, Rapaflo, Silodyx, others|
|Other names||KAD-3213, KMD-3213|
|Drug class||α1-adrenoceptor antagonist|
|Main uses||Benign prostatic hyperplasia (BPH)|
|Side effects||Retrograde ejaculation, dizziness, low blood pressure with standing, stuffy nose|
|Typical dose||8 mg OD|
|Metabolism||Liver glucuronidation (UGT2B7-mediated); also minor CYP3A4 involvement|
|Elimination half-life||13±8 hours|
|Excretion||33.5% renal, 54.9% fecal|
|Chemical and physical data|
|Molar mass||495.543 g·mol−1|
|3D model (JSmol)|
Silodosin, sold under the brand name Rapaflo among others, is a medication used to treat benign prostatic hyperplasia (BPH). It may be used together with a 5α-reductase inhibitor. It is taken by mouth.
Common side effects include retrograde ejaculation, dizziness, low blood pressure with standing, and a stuffy nose. Other side effects may include intraoperative floppy iris syndrome. Use is not recommended in people with significant liver or kidney problems. It is an α1-adrenoceptor antagonist which help muscles in the bladder and prostate relax.
The typical dose is 8 mg once per day.
According to European labels, silodosin has no contraindications apart from known hypersensitivity. Another source names recurring urinary retention, recurring urinary infections, uncontrolled macrohematuria, bladder stones, hydronephrosis, combination with other α1-antagonists or dopamine agonists, and severe renal or hepatic impairment as contraindications.
Other common adverse effects (in more than 1% of patients) are dizziness, orthostatic hypotension, diarrhoea, and clogged nose. Less common (0.1–1%) are tachycardia (fast heartbeat), dry mouth, nausea, skin reactions, and erectile dysfunction. Hypersensitivity reactions occur in fewer than 0.01% of patients. There have been reports about intraoperative floppy iris syndrome during cataract extractions. These side effects are similar to those of other α1 antagonists.
Combining silodosin with strong inhibitors of the liver enzyme CYP3A4, such as ketoconazole, significantly increases its concentrations in the blood plasma and its 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.
Mechanism of action
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 BPH.
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.
Silodosin is almost completely excreted in form of its 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.)
Kissei licensed the US, Canadian, and Mexican rights for silodosin to Watson Pharmaceuticals (now Allergan) in 2004. The United States Food and Drug Administration and Health Canada approved silodosin under the brand name Rapaflo on 9 October 2008 and 11 January 2011, respectively.
Society and culture
Other brand names include Urorec (European Union), Niksol (Croatia), Silorel (Jamaica), Sildoo, Silodal, Silodosia, Silofast (India) Thrupas (South Korea), Flopadex (Egypt), and Urorec (Russia).
As α1A adrenoceptor antagonists are being investigated as a means to male birth control due to their ability to inhibit ejaculation but not orgasm, a trial with 15 male volunteers was conducted. While silodosin was completely efficacious in preventing the release of semen in all subjects, 12 out of the 15 patients reported mild discomfort upon orgasm. The men also reported the psychosexual side effect of being strongly dissatisfied by their lack of ejaculation.
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