Urerek capsules 4mg, No. 30

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 can 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.

Elderly patients

No dose adjustment is required for elderly patients.

Application in children

The drug Urorek has not been used in pediatric practice for these indications.

Hard gelatin capsules

1 caps.

silodosin

Excipients: mannitol, pregelatinized starch, pregelatinized starch (PCS Щ PC-10 starch), sodium lauryl sulfate, magnesium stearate.

• 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).

pharmachologic effect

Highly selective competitive antagonist of ? 1A-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 ? 1A-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 ?1A-adrenergic receptors is 162 times higher than its ability to interact with ?1B-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.

Pharmacokinetics

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, carbamoyl glucuronide (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.

Side effect

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 in accordance with 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 side of 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.

On the part of the hepatobiliary system: infrequently - abnormal liver function indices *.

On the part of the skin and subcutaneous tissue: infrequently - rash , pruritus , urticaria , drug dermatitis .

From the genitals and mammary gland: very often - retrograde ejaculation, anejaculation; infrequently - erectile dysfunction.

Injury, poisoning and complications of procedures: frequency unknown - intraoperative syndrome of 'flabby' iris during cataract surgery.

* 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 events in the course of clinical studies 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.

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

When treating patients with moderate renal insufficiency (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.

special instructions

As with the use of other alpha1-blockers, a decrease in blood pressure and orthostatic hypotension can be observed during treatment with silodosin. Patients with a history of orthostatic hypotension are not advised to take silodosin. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down and remain in this position until the symptoms of orthostatic hypotension disappear.

Since benign prostatic hyperplasia and malignant prostatic tumor have similar symptoms and can develop together, patients with suspected benign prostatic hyperplasia need to be examined before prescribing the drug to exclude malignant prostate tumor.

Digital rectal examination and, if necessary, PSA determination should be performed before starting treatment and at regular intervals after it.

Treatment with silodosin can lead to a decrease in the amount of semen produced during orgasm, which can temporarily affect male fertility. This effect disappears after you stop taking silodosin.

In patients taking or taking alpha-1-blockers during cataract surgery, intraoperative flabby iris syndrome (ISDR) may occur, which can lead to complications during surgery. Patients who are scheduled for cataract surgery are not advised to start treatment with silodosin. It is recommended that treatment with alpha-1 blockers be discontinued 1Ц2 weeks prior to such surgery, but the benefits and duration of discontinuation prior to cataract surgery have not yet been established.

In a preliminary assessment before surgery, surgeons and ophthalmologists should take into account whether patients who are scheduled for this operation have taken or are taking silodosin in order to take appropriate measures to manage and control ISDR.

Influence on the ability to drive vehicles and mechanisms

There have been no studies of the effect of silodosin on the ability to drive vehicles and equipment. Patients should be informed about the possible manifestations of symptoms associated with orthostatic hypotension (for example, dizziness), and if they occur, refrain from driving and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: Silodosin was evaluated at 48 mg / day in healthy men. The dose-dependent adverse reaction was postural hypotension.

Treatment: with recent ingestion, initiation of vomiting or gastric lavage is possible. If an overdose of Urorek has led 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%).

Drug interactions

Silodosin is extensively metabolized mainly by CYP3A4, alcohol dehydrogenase and UGT2B7. Silodosin is also a substrate for P-glycoprotein. Substances that inhibit or induce these enzymes and transporters can affect the plasma concentration of silodosin and its active metabolite.

Alpha blockers

There is no sufficient information on the safety of co-administration of silodosin and other alpha-blockers. Therefore, the simultaneous use of other alpha-adrenergic receptor antagonists is not recommended.

CYP3A4 inhibitors

In an interaction study, a 3.7-fold increase in the plasma Cmax of silodosin and a 3.1-fold increase in the effect of silodosin (i.e., AUC) were found with the simultaneous administration of a potent CYP3A4 inhibitor (ketoconazole 400 mg). Concomitant use with potent CYP3A4 inhibitors (such as ketoconazole, itraconazole and ritonavir) is not recommended.

When silodosin and a moderate CYP3A4 inhibitor, for example, diltiazem, were taken together, there was an approximately 30% increase in the AUC of silodosin, but there was no effect on the Cmax and T1 / 2 values. This change is not clinically important and no dose adjustment is required.

PDE-5 inhibitors

Only minimal pharmacodynamic interaction was observed between silodosin and the maximum dose of sildenafil or tadalafil. In a placebo-controlled study, in 24 people aged 45-78 years who received silodosin, the simultaneous administration of sildenafil 100 mg or tadalafil 20 mg caused a clinically insignificant mean decrease in systolic or diastolic blood pressure, which was assessed during the orthostatic test (the difference in heart rate while lying and standing ). In patients over 65 years of age, the average decrease at various points in time was between 5 and 15 mm Hg. (systolic) and between 0 and 10 mm Hg. (diastolic). Positive orthostatic test results were only marginally more frequent during coadministration, but no symptomatic orthostasis or dizziness was reported. Condition of patientssimultaneously receiving PDE-5 inhibitors and the drug should be monitored for the possible development of adverse reactions.

Antihypertensive drugs

In accordance with the program of the clinical study, many patients received concomitant therapy with antihypertensive drugs (mainly drugs acting on the renin-angiotensin system, beta-adrenal locators, calcium antagonists and diuretics) without increasing the incidence of orthostatic hypotension. However, it is necessary to take precautions while using the drug with antihypertensive drugs. The patient's condition should be monitored for the possible development of adverse reactions.

Digoxin

With the simultaneous administration of silodosin 8 mg 1 time / day, there was no significant effect on the plateau of the concentrations of digoxin, a substrate of P-glycoprotein. No dose adjustment is required.