Urorek

General characteristics. Structure:

Active agent: силодозин 4 mg

Excipients: Mannitolum - 132.4 mg, starch prezhelatinizirovanny (starch of 1500 - 9 mg, PCS PC-10 starch - 26 mg), sodium lauryl sulfate - 1.8 mg, magnesium stearate - 1.8 mg.

Structure of a gelatin capsule: gelatin - 47.434 mg, titanium dioxide - 480 mkg, dye ferrous oxide yellow (E172) - 86 mkg.

Active agent: силодозин 8 mg

Excipients: Mannitolum - 264.8 mg, starch prezhelatinizirovanny (starch of 1500 - 18 mg, PCS PC-10 starch - 52 mg), sodium lauryl sulfate - 3.6 mg, magnesium stearate - 3.6 mg.

Structure of a gelatin capsule: gelatin - 98 mg, titanium dioxide - 2 mg, dye ferrous oxide yellow (E172) - 86 mkg.

Pharmacological properties:

Pharmacodynamics. Silodozin is drug of selective action, the antagonist α1А-адренорецепторов which contain preferential in a prostate, day of a bladder, in a bladder neck, the capsule of a prostate and prostatic part of an urethra. Blockade of data α1А-адренорецепторов provides relaxation of unstriated muscles of this department which, in turn, increases the speed of outflow of urine (Qmax), owing to what the symptoms of irritation and obstruction caused by the benign hyperplasia of a prostate (BHP) disappear.
Silodozin is characterized much more by smaller affinity to α1B-адренорецепторам which are localized preferential in fabrics of cardiovascular system. The researches in vitro showed that ability of a silodozin to communicate with α1А-and α1B - adrenoceptors corresponds as 162:1. It is authentically known that improvement of symptomatology on a scale of the American urological association is provided at reception of a silodozin in a dose of 4 or 8 mg much better, than at placebo reception.

Pharmacokinetics. Pharmacokinetic characteristics of a silodozin were estimated at administration of drug by the male adult patients healthy or sick DGPZh after one-time and/or reusable reception in doses of 0,1-48 mg/days. In the specified range of doses pharmacokinetic characteristics of a silodozin change linearly.
Absorption
Silodozin in case of peroral introduction is well acquired by an organism, value of absorption is proportional to the entered dose. Absolute biological availability of drug makes about 32%. In case of administration of drug with food Cmax value decreases approximately by 30%, Tmax increases approximately by 1 h, change of AUC value is not observed. After oral administration of 8 mg of drug of 1 times a day right after a breakfast such indicators are defined: Cmax — 87±51 mg/ml (3), Tmax — 2,5 h (range 1,0–3,0), AUC — 433±286 нг/ч/мл, T½ — 11 h (range of 7-17 h).

Distribution. The volume of distribution of a silodozin makes 49,5 l, drug for 96,6% contacts proteins of a blood plasma.
Biological transformation
Metabolism of a silodozin is carried out due to processes of a glyukuronidation and oxidation, with the participation of enzymes of alcohol dehydrogenase and an aldegiddegidrogenaza. The main metabolite in a blood plasma — the conjugated glucuronide of a silodozin (KMD-3213G) which activity is confirmed to in vitro — is characterized by more long T½ (about 24 h), its concentration in a blood plasma approximately by 4 times exceeds value of concentration of the silodozin. Silodozin has no the inhibiting or potentiating effect on isoenzymes of system of P450 cytochrome.

Removal. After oral administration of a silodozin about 33,5% also 54,9% — with a stake are removed with urine. The general clearance of a silodozin makes about 23,1 l/h Silodozin is brought preferential in the form of metabolites, and only extremely insignificant percent of drug in not changed look is removed with urine. Terminal T½ of drug makes about 11 h.

Pharmacokinetics in special groups of patients. Patients of advanced age
Characteristics of influence of a silodozin and its main metabolites do not depend on age of the patient. The general clearance of a silodozin remains invariable and in case of administration of drug by patients of 85-year age.
Abnormal liver function
Pharmacokinetic characteristics of a silodozin are identical as at patients with an abnormal liver function of moderate severity (assessment on a scale of Child-Pugh of 7-9 points), and at healthy patients. Researches of pharmacokinetic characteristics in case of abnormal liver functions of high severity were not conducted.

Renal failure. The research of results of use of a single dose showed that Cmax and AUC value of a silodozin (untied) at reception by patients with a renal failure with insignificant or moderate severity raise in 1,6 and 1,7 times respectively in comparison with indicators at patients with normally functioning kidneys. At patients with a renal failure of high severity increase in indicators of Cmax by 2,2 times and AUC — by 3,7 times was observed. Value of pharmacokinetic characteristics of the main metabolites of drug, a silodozin of a glucuronide and KMD3293, increased in proportion to degree of a renal failure, T½ also raised in proportion to extent of disturbance.
The general concentration of a silodozin after 4 weeks of reception by patients with a renal failure of low severity same as at patients with normally functioning kidneys, and at patients with a renal failure of moderate severity concentration of drug increases twice.
Viewing of all data on safety of drug demonstrates that therapy silodoziny in case of a renal failure of low severity is not associated with growth of risk of dizzinesses or orthostatic hypotension in comparison with therapy at patients with normally functioning kidneys. So, dose adjustment for patients with a renal failure of easy severity is not required. Due to the limitation of data on results of administration of drug by patients with a renal failure of moderate severity the initial recommended dose of drug makes 4 mg. Use of a silodozin in therapy of patients with a renal failure of heavy degree is contraindicated.

Indications to use:

Symptomatic treatment at DGPZh.

Route of administration and doses:

Adults. Apply inside. The recommended dose makes 8 mg of 1 times a day. Drug should be accepted together with food, it is desirable at the same time days. The capsule to break, swallow chewing, washing down with a glass of water.
Patients of advanced age
Silodozin appoint with care to patients of advanced age in connection with the increased risk of developing of arterial hypotension. Dose adjustment for patients of advanced age is not required (see Pharmacokinetics).
Patients with a renal failure
Dose adjustment for patients with an insignificant renal failure (clearance of creatinine ≥50 — <80 ml/min.) is not required. In case of a renal failure of moderate severity (clearance of creatinine ≥30 — <50 ml/min.) therapy begin with a dose 4 mg of a silodozin of 1 times a day then, considering individual reaction of an organism, in 1 week the dose can be raised to 8 mg of 1 times a day. Use of drug in therapy of patients with a heavy renal failure (clearance of creatinine <30 ml/min.) it is contraindicated.
Patients with an abnormal liver function
Dose adjustment for patients with insignificant or moderated to abnormal liver functions is not required. As there is no clinical experience of use of drug in therapy of patients with a heavy abnormal liver function, prescription of medicine is contraindicated to patients of this category.

Features of use:

Monotherapy silodoziny is not recommended to patients with coronary insufficiency. Specific treatment of coronary insufficiency should be continued. In case of resuming or deterioration in stenocardia therapy silodoziny needs to be stopped.
The intraoperative syndrome of a flabby iris of the eye (option of a syndrome of sluggish reaction of a pupil) was observed during surgery in connection with a cataract at some patients accepting blockers α1-адренорецепторов or accepting them earlier. Such phenomenon can increase risk of procedural complications during operation.
Patients are not recommended to carry out therapy silodoziny before planned operation in connection with a cataract. The termination of therapy using blockers α1-адренорецепторов one week prior to surgery on removal of a cataract is obligatory.
In the period of a preparation for surgery ophthalmologists have to find out whether the patient accepts or accepted силодозин earlier to apply appropriate measures to avoidance of an intraoperative syndrome of a flabby iris of the eye in a case of its manifestation.

Orthostatic phenomena
At some patients the ABP can decrease that leads to a loss of consciousness. At the first symptoms of orthostatic hypotension (for example orthostatic dizziness) the patient it is necessary to seat or help to adopt horizontal provisions before disappearance of symptoms. Therapy silodoziny is not recommended to patients who have orthostatic hypotension. With care appoint силодозин to patients who have in the anamnesis the expressed arterial hypotension after use of other blocker α1-адренорецептора.

Renal failure
Dose adjustment for patients with an insignificant renal failure (the clearance of creatinine ≥50-<80 ml/min.) is not required. In case of a moderate renal failure (≥30– <50 ml/min.) therapy begin with a dose 4 mg of 1 times a day which taking into account individual reaction of an organism in 1 week can be raised to 8 mg of 1 times a day. Use of drug in therapy of patients with a heavy renal failure (clearance of creatinine <30 ml/min.) it is contraindicated.

Abnormal liver function
Dose adjustment for patients with an abnormal liver function from low to moderate severity is not required. Use of a silodozin in therapy of patients with a heavy abnormal liver function is contraindicated as there is no necessary information.
Prostate carcinoma
Because DGPZh and a carcinoma of a prostate are followed by identical symptoms, and both of these diseases can proceed at the same time before appointing to the patient therapy silodoziny in connection with DGPZh, it is necessary to exclude existence of a carcinoma of a prostate.

Reproductive ability
At patients cases of a retrograde ejaculation (approach of an orgasm with a limited ejaculation or without ejaculation) against the background of therapy silodoziny are noted. It is necessary to report to the patient about a possibility of cases of a retrograde ejaculation prior to performing therapy.
In case of surgical intervention
The anesthesiologist should be informed on what the patient accepts or accepted силодозин.

Use during pregnancy and feeding by a breast. Silodozin is intended only for therapy of male patients.
Children. Do not apply in pediatric practice.
Ability to influence speed of response at control of vehicles or work with other mechanisms. Specialized researches for definition of influence of drug on ability to manage vehicles, by other equipment were not conducted. Patients should be warned about possibility of the phenomena caused by orthostatic hypotension and also dizzinesses, losses of consciousness and to warn against control of vehicles or other equipment.

Side effects:

In the table below side reactions taking into account a system and organ class of their manifestation and frequency are specified: very often (≥1/10); often (≥1/100, <1/10); sometimes (≥1/1000, <1/100); seldom (≥1/10 000, <1/1000); very seldom (<1/10 000) and unspecified frequency (in cases when the frequency of reaction cannot be calculated according to the available data). In each group of reaction are specified in process of reduction of gravity of the phenomenon.

System	Very often	Often	Sometimes	Frequency is not established
Disturbances from TsNS		Govokruzheniye		Potyar of consciousness
Disturbances from vascular system		Orthostatic hypotension
Respiratory, thoracic, mediastinal disturbances		Nose congestion
Disturbances from a GIT		Diarrhea	Nausea Dryness in a mouth
Disturbances from reproductive system and mammary glands	Retrograde ejaculation
Injuries, poisonings, procedural complications				Intraoperative syndrome of a flabby iris of the eye

In cases of orthostatic hypotension the loss of consciousness is possible (see. Special INSTRUCTIONS).
The intraoperative syndrome of a flabby iris of the eye (option of a syndrome of sluggish reaction of a pupil) was observed during surgery in connection with a cataract (see. Special INSTRUCTIONS).

Interaction with other medicines:

Blockers of α-adrenoceptors
There is no appropriate information on safety of use of a silodozin in simultaneous therapy with antagonists of α-adrenoceptors. In this regard simultaneous use with other antagonists of α-adrenoceptors is not recommended (see. Special INSTRUCTIONS).

Inhibitors of isoenzymes of the CYP 3A4 system
By results of a research of medicinal interactions it is established that at simultaneous use with strong inhibitors of isoenzymes of the CYP 3A4 system (кетоконазол, 400 mg) Cmax of a silodozin in a blood plasma raises by 3,7 times, and influence of a silodozin (AUC value) — by 3,1 times. Simultaneous use with strong inhibitors of isoenzymes of the CYP 3A4 system (for example кетоконазол, итраконазол or ритонавир) is contraindicated.
At simultaneous use of a silodozin with moderate inhibitors of isoenzymes of the CYP 3A4 system, such as diltiazem, increase in AUC value approximately by 30% was observed, but Cmax and T½ values were left without changes. This change has no clinical value, dose adjustment is not required.

FDE-5 inhibitors
At simultaneous use of a silodozin and sildenafil in a dose of 100 mg or the tadalafila in a dose of 20 mg is observed the minimum pharmakodinamichesky interaction. It is necessary to provide monitoring of patients who accept силодозин combined with FDE-5 inhibitors, in connection with risk of development of postural hypotension, especially at elderly people. Treatment needs to be begun with the lowest recommended dose and to raise gradually in case of need.

Anti-hypertensive drugs
Simultaneous therapy with anti-hypertensive drugs using preferential substances influencing system a renin angiotensin, blockers of β-adrenoceptors, antagonists of calcium and diuretics it is necessary to carry out carefully, having provided monitoring of patients, for early detection of possible side reactions in connection with probability of potentiation of hypotensive action.

Digoxin
Level of concentration of digoxin in a stable state at a concomitant use with silodoziny in a dose of 8 mg of 1 times a day changes slightly. It is necessary to apply with care силодозин at patients who receive therapy by cardiac glycosides. Treatment silodoziny needs to be carried out with simultaneous control of the ABP; therapy of such patients should be begun with the lowest recommended dose and to gradually raise it in case of need. In case of individual hypersensitivity at patients emergence of dizziness is possible.

Contraindications:

• hypersensitivity to a silodozin or any of drug excipients;
• heavy renal failures (clearance of creatinine <30 ml/min.);
• heavy abnormal liver functions;
• the combined use with strong inhibitors of the CYP 3A4 system (for example кетоконазол, итраконазол or ритонавир);
• one week prior to carrying out surgery on removal of a cataract;
• dekompensirovanny heart failure.

Overdose:

Symptom of overdose is orthostatic hypotension.
Treatment: to immediately cause vomiting or to carry out a gastric lavage. In cases when the overdose silodoziny is followed by hypotonia, it is necessary to provide to the patient support of work of cardiovascular system. For normalization of the ABP and ChSS of the patient it is necessary to put on a back. If it appeared insufficiently, it is necessary in/in administration of physiological solution. It is in case of need allowed uses of vasoconstrictive drugs on condition of continuous monitoring of function of kidneys and its support. Carrying out dialysis is inexpedient because силодозин in an organism almost completely (97%) contacts proteins.

Storage conditions:

Drug should be stored in dry, protected from light, the place, unavailable to children, at a temperature not above 30 °C.

Issue conditions:

According to the recipe

Packaging:

In packagings of planimetric cell PVC / PVDH / aluminum foil on 5 or 10 pieces; in a pack of cardboard 1, 2, 3, 5, 9 or 10 packagings of planimetric cell.