Drug information of silodosin

silodosin


Silodosin is an α1-adrenoceptor antagonist that is selective for the prostate. Silodosin is for symptomatic treatment of benign prostatic hyperplasia. FDA approved Oct 9, 2008.

Mechanism of effect

Silodosin is a selective antagonist of alpha1A-adrenoreceptors in the prostate and bladder. Smooth muscle tone in the prostate is mediated by alpha1A-adrenoreceptors; blocking them leads to relaxation of smooth muscle in the bladder neck and prostate causing an improvement of urine flow and decreased symptoms of BPH. Approximately 75% of the alpha1-receptors in the prostate are of the alpha1A subtype.

Pharmacodynamic

Silodosin is 583 times more selective for human alpha-1A receptors than alpha-1B receptors. It is also 56 times more selective for human alpha-1A receptors than alpha-1D. Silodosin does not prolong the QT interval.

Pharmacokinetics

Absorption:
Quickly absorbed and has a bioavailability of 32% at 8mg/day (therapeutic dose). When 8 mg of silodosin is taken once daily with food, the pharmacokinetic parameters are as follows: Cmax = 61.6 ± 27.54 ng/mL; Tmax = 2.6 ± 0.90 hours;
AUC (0h-24h) = 373 ng•hr/ml. The AUC of its metabolite, KMD3213G, is four times greater than silodosin.
Volume of destibution:
49.5 L 
Protein binding:
97% bound to protein 
Metabolism:
Extensively metabolized in the liver. The main metabolite is generated via glucuronidation (KMD-3213G) by UDP-2B7. Oxidation by alcohol and aldehyde dehydrogenases produces the second major metabolite, KMD-3293. KMD-3213G accumulates in the plasma as it is very hydrophilic. KMD-3213G is also an active metabolite in which it has 50% of silodosin's inhibitory activity. KMD-3293 is inactive. Cytochrome P450 CYP 3A4 also generates some metabolites. 
Route of elimination:'
Fecal (54.9%);
Renal (33.5%)
Half-life:
Silodosin = 13.3 ± 8.07 hours; KMD-3213G = 24 hours;

Drug indications

Benign Prostatic Hyperplasia

Dosage

Oral: 8 mg once daily with a meal

Drug contraindications

Hypersensitivity to silodosin or any component of the formulation, concurrent use with strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole, ritonavir); severe renal impairment (CrCl <30 mL/minute); severe hepatic impairment (Child-Pugh class C)

Alerts

Use with caution in the elderly (risk of hypotension)
Not indicated for use in women or children
Not for use as hypertensive
Postural hypotension, with or without symptoms (eg, dizziness) may develop when initiating treatment; there is potential for syncope; patients should be cautioned about driving, operating machinery, or performing hazardous tasks when initiating therapy
Dose should be reduced to 4 mg in patients with moderate renal impairment; exercise caution and monitor such patients for adverse events
Not tested in patients with severe hepatic impairment, and therefore, should not be prescribed to such patients; use with caution in patients with mid-to-moderate hepatic impairment
Patients planning cataract surgery should be told to inform their ophthalmologist that they are receiving this therapy; intraoperative floppy iris syndrome observed during cataract surgery in some patients on alpha-1 blockers or previously treated with alpha-1 blockers; variant of small pupil syndrome is characterized by combination of a flaccid iris that billows in response to intraoperative irrigation currents; progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs; and potential prolapse of iris toward phacoemulsification incisions
Carcinoma of prostate and BPH cause many of same symptoms; these two diseases frequently co-exist; patients thought to have BPH should be examined prior to starting therapy to rule out the presence of carcinoma of the prostate

Pregnancy level

B: Teratogenic effects were not observed in animal studies; however, silodosin is not approved for use in women.

Related drugs

Doxazosin , Alfuzosin


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