Symptomatic treatment of benign prostatic hyperplasia (BPH).
active substance: 1 capsule contains 4 mg silodosin;
excipients: mannitol (E 421), corn peptizing starch, purified water, sodium lauryl sulfate, magnesium stearate, gelatin, titanium dioxide (E 171), for dosing 4 mg of iron oxide yellow (E 172).
The capsules are hard.
Highly selective competitive antagonist of α1A-adrenergic receptors, which are mainly located in the prostate gland, in the tissues of the fundus and neck of the bladder, the capsule of the prostate gland and the prostatic part of the urethra.
Blockade of α1A-adrenergic receptors reduces the tone of smooth muscles in these tissues, which leads to an improvement in the outflow of urine from the bladder. At the same time, the symptoms of obstruction and irritation associated with benign prostatic hyperplasia are reduced.
In vitro studies have shown that the affinity of silodosin for α1A-adrenergic receptors is 162 times greater than its ability to interact with α1B-adrenergic receptors, which are located in vascular smooth muscles. Due to its high selectivity, silodosin does not cause a clinically significant decrease in blood pressure in patients with initially normal blood pressure.
Absorption and distribution
After oral administration, silodosin is well absorbed, absorption is proportional to the dose. The absolute bioavailability is about 32%. Food intake reduces Cmax by about 30%, increasing the time to reach Cmax to about 1 hour and has a minimal effect on AUC. After oral administration at a dose of 8 mg 1 time / day immediately after breakfast for 7 days, the following pharmacokinetic parameters were noted: Cmax 87 ± 51 ng / ml (sd), Tmax – 2.5 h (range 1.0-3.0), AUC 433 ± 286 ng × h / ml.
The Vd of silodosin is 0.81 l / kg. Plasma protein binding is 96.6%.
Metabolism and excretion
Silodosin is metabolized by glucuronidation (with the participation of UGT2B7), with the participation of alcohol dehydrogenase and aldehyde dehydrogenase, oxidative pathways, mainly with the participation of CYP 3A4. The main active metabolite in plasma, carbamoylglucuronide (KMD-3213G), reaches a plasma concentration 4 times higher than silodosin itself. The plasma protein binding of silodosin glucuronide is 91%. Silodosin does not have the potential to induce or inhibit cytochrome P450 isoenzymes.
33.5% of silodosin is excreted by the kidneys and 54.9% through the intestines. The clearance of silodosin is about 0.28 l / h / kg. Silodosin is excreted mainly in the form of metabolites and in very small quantities unchanged in the urine. The final T1 / 2 of silodosin and glucuronide is 11 hours and 18 hours, respectively.
Pharmacokinetics in special patient groups
Elderly patients. The pharmacokinetics of silodosin and metabolites did not significantly depend on age. Silodosin clearance does not change in patients over 75 years of age.
Patients with impaired liver function. In patients with moderate liver dysfunction (7-9 points on the Child-Pugh scale), the pharmacokinetics of silodosin does not change significantly. In patients with severe hepatic impairment, the pharmacokinetics of silodosin have not been studied.
Patients with impaired renal function. For patients with mild renal insufficiency (CC ≥50-≤80 ml / min), dose adjustment is not required. For patients with moderate renal insufficiency (CC ≥ 30- <50 ml / min), a low initial dose of 4 mg is recommended. For patients with severe renal insufficiency (CC <30 ml / min), the appointment of silodosin is not recommended.
Indications of the drug Urorek
treatment of symptoms of benign prostatic hyperplasia.
The recommended dose is 8 mg 1 time / day, simultaneously with a meal, preferably at the same time of the day. It is necessary to swallow the capsule whole, preferably with a glass of water.
Patients with impaired renal function
In patients with mild renal insufficiency (CC ≥50-≤80 ml / min), dose adjustment is not required. For the treatment of patients with moderate renal insufficiency (CC ≥30- <50 ml / min), it is recommended to take the drug at an initial dose of 4 mg / day during the first week; with good individual tolerance, the dose may be increased to 8 mg / day. The use of the drug in patients with severe renal insufficiency (CC <30 ml / min) is not recommended.
Patients with impaired liver function
For patients with mild hepatic impairment and with moderate hepatic impairment, dose adjustment is not required. Due to the lack of data, the use of the drug for patients with severe hepatic impairment is not recommended.
No dose adjustment is required for elderly patients.
Application in children
The drug Urorek was not used in pediatric practice for these indications.
The following are undesirable adverse reactions noted in all clinical studies and throughout the international post-marketing experience of use, for which there is a causal relationship, according to the MedDRA classification according to the damage to organs and organ systems and the frequency of development: very often (≥1 / 10), often (from? 1/100 to <1/10), infrequently (from? 1/1000 to <1/100), rarely (from? 1/10 000 to <1/1000), very rarely (from <1 / 10,000), the frequency is unknown (the frequency cannot be determined from the available data).
From the immune system: very rarely – allergic reactions – angioedema of the face, tongue and larynx *.
Mental disorders: infrequently – decreased libido.
From the nervous system: often – dizziness; rarely – loss of consciousness *; frequency unknown – syncope.
From the heart: infrequently – tachycardia *; rarely – palpitations *.
From the side of the vessels: often – orthostatic hypotension; infrequently – a decrease in blood pressure *.
From the respiratory system, chest and mediastinal organs: often – nasal congestion.
From the digestive system: often – diarrhea; infrequently – nausea, dry mouth.
From the hepatobiliary system: infrequently – abnormal liver function indices *.
On the part of the skin and subcutaneous tissue: infrequently – rash *, itching *, urticaria *, drug dermatitis *.
On the part of the genitals and breast: very often – retrograde ejaculation, anejaculation; infrequently – erectile dysfunction.
Injuries, poisoning and complications of procedures: frequency is unknown – intraoperative syndrome of “flabby” iris during cataract operations.
* side effects registered spontaneously in the course of international post-marketing experience of use (the frequency of occurrence was calculated based on the occurrence of phenomena in the course of clinical trials of I-IV phases and non-interventional studies).
Orthostatic hypotension: The incidence of orthostatic hypotension in placebo-controlled clinical trials was 1.2% in the silodosin group and 1% in the placebo group. Orthostatic hypotension can sometimes cause fainting.
Intraoperative Flabby Iris Syndrome (ISDR): It has been reported that ISDR developed during cataract surgery.
If any of the side effects indicated in the instructions are aggravated or the patient has noticed any other side effects, he should inform the doctor about it.
Contraindications for use
- severe renal failure (CC <30 ml / min);
- severe hepatic impairment (insufficient clinical data);
- children and adolescents up to 18 years old;
- hypersensitivity to the active substance or any of the auxiliary components or their intolerance.
It should be used with caution in case of mild and moderate renal failure (CC from 30 to 50 ml / min).
Application during pregnancy and lactation
Silodosin is for men only.
Application for violations of liver function
The drug is contraindicated in patients with severe hepatic impairment (insufficient clinical data).
Application for impaired renal function
In the treatment of patients with moderate renal failure (CC ≥30- <50 ml / min), it is recommended to take the drug at a dose of 4 mg / day during the first week, then, with good individual tolerance, the dose can be increased to 8 mg / day.
In severe renal failure (CC <30 ml / min), the appointment of silodosin is contraindicated.
Application in children
The use of the drug in children and adolescents under the age of 18 is contraindicated.
Symptoms: Silodosin has been evaluated at 48 mg / day in healthy men. Postural hypotension was a dose-dependent adverse reaction.
Treatment: with recent ingestion, initiation of vomiting or gastric lavage is possible. If an overdose of Urorek leads to arterial hypotension, it is necessary to take measures to support the patient’s cardiovascular system. Dialysis is unlikely to produce significant results because silodosin actively binds to blood proteins (96.6%).
Storage conditions of the drug Urorek
The drug should be stored in a dark place at a temperature not exceeding 25 ° С
Shelf life of the drug Urorek
The shelf life is 3 years.