Urorek, 8 mg capsules 30 pcs

Pharmacodynamics.

The mechanism of action

. Silodosin, a highly selective competitive antagonist of alpha 1a-adrenoreceptors, blocks postsynaptic alpha 1a-adrenoreceptors located in the smooth muscle of the prostate, bladder neck and prostatic part of the urethra.

It reduces tone of the smooth muscles of the prostate, bladder neck and the prostatic part of the urethra, improving the outflow of urine. At the same time the symptoms of obstruction and irritation associated with benign prostatic hyperplasia are reduced.

The affinity to alpha| 1a-adrenoreceptors located in the urinary bladder is 162 times higher than its ability to interact with alpha-1b-adrenoreceptors located in vascular smooth muscle. Due to high selectivity, it does not cause clinically significant reduction of arterial pressure (BP) in patients with baseline normal BP.

Pharmacokinetics

Silodosine is well absorbed when taken orally. Absolute bioavailability is 32%. Food reduces maximum concentration (Cmax) by approximately 30%, extending the time to reach maximum concentration (tmax) to approximately 1 h and has minimal effect on the area under the concentration-time curve (AUC).

Cmax87±51 mg/mL, tmax 2.5 h, urinary mean concentration 433±286 ng*h/mL. The volume of distribution of silodosine is 0.81 l/kg and is bound to plasma proteins by 96.6%. Binding of silodosine carbamoylglucuronide by plasma proteins is 91%. Silodosine is metabolized through glucuronidation (involving UGT2B7), with the participation of alcohol dehydrogenase and aldehyde dehydrogenase, oxidative pathways, mainly involving CYP3A4.

The main active metabolite in plasma is carbamoylglucuronide (K.MD-3213G), which reaches a plasma concentration 4 times higher than silodosine itself. Silodosin has no potential to induce or inhibit cytochrome P450 isoenzymes.

33.5% of silodosine is excreted through the kidneys and 54.9% through the intestine. Clearance of silodosine is about 23.1 L/h. Silodosin is excreted mainly as metabolites and in very small amounts unchanged in the urine. T1/2 of silodosine and carbamoylglucuronide is 11 hours and 18 hours, respectively.

Pharmacokinetics in different groups of patients

Elderly patients: pharmacokinetics of silodosin and metabolites were not significantly dependent on age. Clearance of silodosine did not change in patients older than 75 years. Patients with impaired liver function: In patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale), the pharmacokinetics of silodosine did not change significantly. In patients with severe hepatic impairment, the pharmacokinetics of silodosin have not been studied.

Patients with impaired renal function: No dose reduction was required for patients with moderate renal impairment. For patients with severe renal impairment, administration of silodosin is not recommended.

Indications

Urorek is designed to treat benign prostatic hyperplasia.

Active ingredient

Composition

Composition per capsule:

Active ingredient:

silodosin 4 mg or 8 mg.

Associates:

Mannitol, pregelatinized starch (starch 1500™),

Pregelatinized starch (PCS™ PC-10 starch),

sodium lauryl sulfate, magnesium stearate.

Composition of the gelatin capsule:

gelatin,

titanium dioxide,

iron oxide yellow dye (E-172)

How to take, the dosage

The recommended dose is 8 mg once with a meal, preferably at the same time of day. the capsule should be swallowed whole, preferably with a glass of water.

To treat patients with moderate renal insufficiency (creatinine clearance >30 -<50 ml/min), an initial dose of 4 mg daily is recommended for the first week, then the dose can be increased to 8 mg daily if well tolerated individually.

Interaction

Combination with other alpha-adrenoblockers is not recommended because of possible potentiation of action.

The co-administration of CYP3A4 isoenzyme inhibitors (ketoconazole, clarithromycin, itraconazole, ritonavir) is not recommended because it increases the plasma concentration of sildosine.

Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) when used together may increase the risk of dizziness.

Hypotensive drugs beta-adrenoblockers, calcium antagonists, drugs acting on the renin-angiotensin aldosterone system, diuretics when used together increase orthostatic hypotension.

Special Instructions

As with other alpha1-adrenoblockers, a decrease in BP, orthostatic hypotension may be observed during treatment with 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.

Because benign prostatic hyperplasia and prostate tumors have similar symptoms and may occur together, patients with suspected benign prostatic hyperplasia should be evaluated to rule out prostate tumors before the drug is prescribed.

In patients who are taking or have taken alpha1-adrenoblockers, “flabby” iris syndrome may occur during cataract surgery, which may lead to complications during surgery. Treatment with alpha1-adrenoblockers should be discontinued 1-2 weeks prior to such surgery. Patients who are scheduled for cataract surgery are not recommended to start treatment with Urorek.

Impact on the ability to drive vehicles and operate machinery: No studies have been conducted on the effect on the ability to operate vehicles and equipment. However, patients should be informed about possible manifestations of symptoms associated with orthostatic hypotension (e.g. dizziness) and warned not to drive vehicles and equipment until the patient’s individual tolerance to Urorek has been established.

Contraindications

Side effects

Unwanted reactions by frequency are as follows: very common: >10, common: > 1/100 to < 1/10, infrequent: > 1/1000 to < 1/100, rare: > 1/10 000 to < 1/1000, frequency unknown (available data do not allow to determine frequency).

Nervous system

Often: dizziness.

Frequency unknown: syncope

Cardiovascular system

Often: orthostatic hypotension.

Respiratory system

Often: nasal congestion.

Gastrointestinal tract

Often: diarrhea.

Infrequent: nausea, dry mouth.

Reproductive system

Very common: Retrograde ejaculation, anejaculation

Infrequent; decreased libido, erectile dysfunction

Intraoperative syndrome

Frequency unknown:

Intraoperative “flabby” iris syndrome during cataract surgery.

Overdose

Symptoms: marked BP decrease, compensatory tachycardia.

Treatment: gastric lavage, administration of activated charcoal or osmotic laxative, symptomatic therapy to increase circulating blood volume (RBC), vasoconstrictor drugs. Control of renal function. Dialysis is ineffective due to intense binding of the drug to plasma proteins.

Pregnancy use

Urorek is contraindicated in children under 18 years of age, pregnant women and during lactation.