active ingredient: 1 capsule contains 4mg or 8mg of silodosin;
auxiliary substances: mannitol (E 421), peptisation starch corn, purified water, sodium lauryl sulfate, magnesium stearate, gelatin, titanium dioxide (E 171), for dosing 4 mg iron oxide yellow (e 172).
Basic physico-chemical properties:
hard capsules containing 4 mg silodosin,
hard capsules containing 8 mg silodosin.
Antagonists of ?-adrenergic receptors. Silodosin.
Code ATX G04С A04, collect statistical agencies.
Silodosin is a drug of high selective action, an antagonist of ? 1A-adrenoreceptors, contained mainly in the prostate gland, at the bottom of the bladder, in the bladder neck, in a capsule of the prostate and prostate urethra. The blockade of ? 1A-adrenoreceptor data provides relaxation of the smooth muscle of this Department, which, in turn, increases the rate of urine outflow without affecting the contractility of the smooth muscles of the detrusor. As a result, symptoms of irritation and obstruction caused by benign prostatic hyperplasia (BPH) disappear.
Silodosin is characterized by a much lower affinity to ? 1 B -adrenergic receptors, which are localized mainly in tissues of the cardiovascular system.
Studies in vitro have shown that the ability silodosin to contact the adrenergic receptors ? 1A and ? 1 B corresponds to 162: 1.
It is known that the improvement of symptoms on a scale of the American urological Association (AUA) is provided at the reception silodosin at a dose of 4 mg or 8 mg significantly better than when taking a placebo. Clinical studies conducted in the United States and Europe with silodosin at a dose of 8 mg once a day showed a significant decrease in the symptoms of BPH both accumulation (irritation) and release (obstruction) compared to placebo, according to the International scale of prostate symptoms assessment (international Prostate Symptom Score, IPSS) after 12 weeks of treatment. During clinical trials conducted in Europe, silodosin at a dose of 8 mg once a day proved to be no less effective at a dose of tamsulosin 0.4 mg once a day. The rate of positive response to treatment, that is, an improvement in the overall assessment of IPSS, was significantly higher in the group taking silodosin and tamsulosin, compared to placebo.
In the long-term open extended phase of these clinical trials, in which patients received silodosin up to 1 year, improvement in symptoms influenced by silodosin in the 12th week of treatment persisted for more than 1 year.
In phase IV of the clinical trial, which was conducted in Europe according to the International scale of prostatic symptoms evaluation, 77.1% of patients had a response to treatment. Approximately half of the patients with the most annoying symptoms, namely, nocturia, increased frequency of urination, weak stream, urgent need to urinate, leakage of urine at the end of urination and incomplete emptying of the bladder, reported improvement, as specified in the questionnaire of the International organization on problems of incontinence of urine (International Continence Society, ICS) for men.
In all clinical studies, was carried out under the condition of taking silodosin, there was no significant decrease in blood pressure in the patient in a horizontal position.
Silodosin at a dose of 8 mg and 24 mg per day compared with placebo has no statistically significant effect on ECG intervals or heart repolarization.
Pharmacokinetic characteristics silodosin and its major metabolites were evaluated when the drug in adult male patients, healthy or sick BPH after single and/or repeated administration in doses of from 0.1 mg to 48 mg per day. In the specified dose range pharmacokinetic characteristics of silodosin vary linearly.
Exposure of the main metabolite, silodosin glucuronide (KMD-3213G), in plasma at steady state is 3 times greater than the initial drug. Silodosin and glucuronide reach a state of equilibrium after 3 days and 5 days of treatment, respectively.
Silodosin when administered orally, well absorbed by the body, the value of absorption in proportion to the administered dose. The absolute bioavailability of the drug is about 32%.
In vitro studies with cells Caco-2 showed that silodosin is a substrate of P-glycoprotein.
In the case of taking the drug with food, the value of max decreases by about 30%, t max increases by about 1:00, the change in the value of AUC is not observed. After taking 8 mg 1 time a day immediately after Breakfast for 7 days, the following pharmacokinetic parameters were determined: with max-87 ± 51 ng/ml (SW), t max-2.5 hours (range 1.0-3, 0), AUC-433 ± 286 ng/h/ml.
The volume of distribution is silodosin of 0.81 l/kg. Silodosin 96.6% is associated with blood plasma proteins. It is not distributed in red blood cells.
Protein binding silodosin glucuronide is 91%.
Metabolism of silodosin is carried out by glucuronization processes (UGT2B7), alcohol and aldehyde dehydrogenase and oxidation, mainly CYP3A4. The major metabolite in plasma - conjugated silodosin glucuronide (KMD-3213G), the activity of which is confirmed by W vitrо is characterized by a longer half-life (approximately 24 hours), its concentration in plasma is about 4 times larger than the value of the concentration of silodosin. The data in vitro indicate that silodosin has no potenziruet or inhibitory effect on the isozymes of cytochrome P450.
After taking silodosin after 7 days approximately of 33.5% is excreted in urine and 54.9% in feces. Total clearance is approximately silodosin 0,28 l/h/kg. Silodosin is excreted predominantly as metabolites, and only an extremely small percentage of the drug in unchanged form excreted in the urine. The terminal half-life of the unchanged drug and its glucuronides is approximately 11:00 and 18 hours, respectively.
Pharmacokinetics in special groups of patients.
Patients of advanced age.
Characteristics of exposure to silodosin and its main metabolites do not depend on the age of the patient. The overall clearance of silodosin remains unchanged in the case of patients over 75 years of age.
The effect of silodosin was evaluated in patients under the age of 18.
Impaired liver function.
Pharmacokinetic characteristics silodosin are the same both in patients with impaired liver function of moderate severity (rating on the scale of child-Pugh 7-9 points) and in healthy volunteers. The results of this study should be interpreted with caution because the patients had normal biochemical parameters, indicating normal metabolic function, and they were classified as patients with impaired liver moderate taking into account ascites and hepatic encephalopathy. Silodosin pharmacokinetics in patients with severely impaired hepatic function have not been studied.
The impairment of renal function.
A study of the results of the application of a single dose showed that the value of C max and AUC silodosin (unbound) in patients with impaired renal function with mild or moderate severity increased 1.6 and 1.7 fold, respectively, compared to indicators in patients with normally functioning kidneys. In patients with severe impairment of renal function was observed improvement in performance With max 2.2-fold and AUC by 3.7 times. The value of the pharmacokinetic characteristics of the main metabolites of the drug, silodosin glucuronide and KMD3293 also increased.
The concentration of silodosin in blood plasma after 4 weeks of taking patients with impaired renal function of moderate severity is the same as in patients with well-functioning kidneys, and in patients with impaired renal function of moderate severity concentration increases by half.
A review of all data on the safety of the drug indicates that therapy with silodosin in violation of renal function of moderate severity is not associated with increased risk of dizziness or orthostatic hypotension compared with therapy in patients with well-functioning kidneys. So, dose correction for patients with impaired renal function of moderate severity is not required. Due to the limited data on the results of taking the drug in patients with impaired renal function of moderate severity, the initial recommended dose of the drug is 4 mg. The use of silodosin in the treatment of patients with impaired renal function is not recommended.
Symptomatic treatment of benign prostatic hyperplasia (BPH).
Hypersensitivity to silodosin or any of the auxiliary substances in the preparation.
Interaction with other medicinal products and other forms of interaction
Silodosin is actively metabolized, especially CYP3A4, alcohol dehydrogenase and UGT2B7. Silodosin also acts as a substrate for P-glycoprotein. Substances that inhibit or induce these enzymes and carriers may affect plasma concentrations of silodosin and its active metabolites.
There is no adequate information about the safety of silodosin use in simultaneous therapy with ?-adrenoreceptor antagonists. In this regard, simultaneous use with other antagonists of ?-adrenoreceptors is not recommended (see section "peculiarities of application").
Inhibitors of the isoenzyme system СУРЗА4.
According to the results of the study of drug interactions it was found that the maximum concentration of silodosin in blood plasma increases by 3.7 times, while the use of isozain inhibitors of the SURZA4 system (ketoconazole, 400 mg), and the effect of silodosin (AUC) increases by 3.1 times. The simultaneous use with inhibitors of isoenzyme system СУРЗА4 (such as ketoconazole, Itraconazole or ritonavir) not recommend.
With the simultaneous use of silodosin with moderate isozymes inhibitors SURZA4 system, such as diltiazem, there was an increase in the value of AUC by about 30%, but the value of the max and the half-life remained unchanged. This change is not of clinical importance, therefore, dose adjustment is not required.
Inhibitors of phosphodiesterase type 5 (РDЕ-5).
With simultaneous use of sildenafil at a dose of 100 mg of tadalafil at a dose of 20 mg, minimal pharmacodynamic interaction was observed, it did not cause a clinically significant decrease in systolic or diastolic blood pressure according to the results of an orthostatic test (in a vertical position against a horizontal position). In patients older than 65 years the mean reduction at different time points were between 5 and 15 mm Hg.art. (Systolic) and 0 and 10 mm Hg.art. (Diastolic). While the use of drugs positive orthostatic samples were not much more frequent; however, cases of symptomatic orthostatic hypotension or dizziness was not. Should monitor patients taking the drug Urorec simultaneously with inhibitors of PDE-5, to avoid possible adverse reactions.
In the clinical trial program, many patients received simultaneous therapy with antihypertensive drugs (mainly substances affecting the renin-angiotensin system, beta-blockers, calcium antagonists and diuretics) without increasing the likelihood of orthostatic hypotension. However, caution should be exercised when taking antihypertensive drugs at the same time; patient monitoring should be ensured to identify possible side effects.
At simultaneous reception with silodosin at a dose of 8 mg once a day, the concentration level of digoxin, a substrate of P-glycoprotein, in a state of equilibrium changed slightly. Dose adjustment is not required.
Intraoperative flaccid iris syndrome.
Intraoperative flaccid iris syndrome (a variant of the syndrome of sluggish reaction of the pupil) was observed during surgery in connection with cataract in some patients who take ? 1-blockers or were taking them before. This complication can increase the risk of procedural complications during surgery.
Patients are not recommended to start drug treatment has Urorec before planned operation in connection with cataracts. It is recommended to discontinue therapy using ? 1 blockers 1-2 weeks before the surgical operation to remove cataracts, but the duration of cessation of therapy in surgical operation in connection with cataracts and the benefits from this have not yet been established.
In preparation for surgery in connection with cataract surgeons and ophthalmologists should find out whether the patient or took earlier drug Urorec, in order to take appropriate measures to prevent syndrome intraoperative flaccid iris during surgery.
Orthostatic phenomena during treatment Urorec are very rare. However, in some patients may decrease blood pressure, in some cases, may lead to loss of consciousness. At the first signs of orthostatic hypotension (for example, in the case of orthostatic dizziness), the patient should be planted or put until the symptoms disappear. Patients suffering from orthostatic hypotension, drug therapy has Urorec is not recommended.
The impairment of renal function.
The use of the drug has Urorec for the treatment of patients with severe impairment of renal function (CL WITH R
Impaired liver function.
The use of the drug has Urorec for the treatment of patients with severe hepatic impairment is not recommended, as there isn't enough information.
Carcinoma of the prostate.
Due to the fact that BPH and prostate carcinoma are accompanied by the same symptoms, and both these diseases can occur simultaneously, and before you assign patient treatment Urorec in connection with BPH, should be ruled out the presence of prostate cancer. You should conduct a digital rectal examination. Also, if necessary, to determine the prostatic specific antigen (PSA) prior to treatment and at regular intervals thereafter.
Drug treatment was Urorec leads to restriction the ejaculation during orgasm and may affect the reproductive ability of men. Cases of retrograde ejaculation (orgasm with a limited ejaculation or no ejaculation) were recorded in patients taking silodosin. This effect disappears after discontinuation of the drug was Urorec.
Before starting therapy, the patient should be informed about the possibility of retrograde ejaculation.
Use during pregnancy or breast-feeding.
Silodosin is intended only for the treatment of male patients.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms.
Specialized studies to determine the effect of the drug on the ability to drive vehicles, other equipment was not carried out. Patients should be warned of the possibility of phenomena caused orthostatic hypotension (such as dizziness), as well as to warn against driving an automobile or other machinery until they know how Urorec effect on their condition.
Method of application and doses
Adult. To apply inside. The recommended dose is 8 mg once a day. For certain groups of patients it is recommended that 1 capsule of the drug was Urorec 4 mg 1 once a day (see Below).
The drug should be taken with food, preferably at the same time of the day. The capsule should be broken, it should be swallowed whole, without chewing, drinking a glass of water.
Patients of advanced age.
Dose adjustment for elderly patients is not required (see section "Pharmacokinetics") .
Patients with impaired renal function.
Dose adjustment for patients with moderate impairment of renal function (CL WITH R from ?50 to < 80 ml/min) is required. In case of violation of renal function moderate (CL WITH R from ?30 to CR
Patients with impaired liver function.
Dose adjustment for patients with moderate to moderate hepatic impairment is not required. Since there is no clinical experience of the drug in the treatment of patients with severe hepatic impairment, the appointment of the drug in this category of patients is not recommended.
Children. Do not use in pediatric practice.
Silodosin was evaluated at doses up to 48 mg/day, which were taken by healthy volunteers of human sex. The dose-limiting adverse reaction was orthostatic hypotension.
If the drug was taken recently, it is recommended that the patient induce vomiting or gastric lavage. If the overdose was Urorec accompanied by hypotension, it is necessary to provide the patient support of the cardiovascular system. Carrying out dialysis is impractical, since silodosin in the body almost completely binds to blood proteins (96.6%).
Common adverse reactions reported during therapy silodosin during placebo-controlled clinical trials and during long-term use, there have been violations of ejaculation, such as retrograde ejaculation, and anejaculation (decrease or absence of ejaculation), with a frequency of 23%. This can temporarily affect a man's reproductive ability. And it is restored a few days after the termination of treatment.
The table below shows adverse reactions reported during all clinical studies in the period poslerevoljutsionnyh of the drug, in accordance with the system-organ class and MedDRA frequency: very often (?1/10); often (?1/100 to <1/10); rare (?1/1,000 to <1/100); rare (from ?1/10,000 to <1/1000); very rare (<1/10000), and unknown frequency (in cases where the frequency of reactions cannot be calculated from available data). In each group, the reactions indicated as the severity of the phenomenon decreases.
system organisating часточастыередкиеодиночныередкиечастота not installed
The immune system Reaction of allergic type, including swelling of the face, swelling of the tongue and pharyngeal-Eden 1
mental disorders decreased libido
From the nervous system Zapatero tion Loss of consciousness of 1 Narita ness
Heart 1Сильное tachycardia palpitations 1
From the vascular system Artistic political hypotensionhypotension 1
Respiratory, thoracic and mediastinal disorders will Lay the nose
The gastro-intestinal tract
diarrhea tract, dry mouth
From the liver and biliary tract Deviation from the norm of the results of studies of liver function 1
The skin and subcutaneous tissue Skin rash 1 itching 1 ,
Nettle-ka 1 , medikamen-side rash 1
From the reproductive system and mammary ultramara ejaculation,
Anacostia erectile dysfunction
Injuries, poisoning and procedural complications Intraoperative flabby iris syndrome
1 - data on adverse reactions received from spontaneous reports during post-registration use in the world (frequency calculated taking into account the cases reported in the I-IV phase of clinical trials and non-interventional studies).
Orthostatic hypotension: the incidence of orthostatic hypotension in placebo-controlled clinical trials was 1.2% in the treatment of silodosin and 1.0% in the treatment of placebo. Orthostatic hypotension can lead to syncope (see Section "Peculiarities of use" ).
Intraoperative syndrome of flabby iris (a variant of sluggish pupil reaction syndrome) was observed during surgical operation in connection with cataract (see section "Peculiarities of application").
Store in the original packaging to protect from light at a temperature not exceeding 30 ° C. Keep out of reach of children.
For dosing of 4 mg: 10 capsules in a blister, 1 or 3 or 5 or 9 blisters in a carton.
For dosing 8 mg: 10 capsules in a blister, 1 or 3 or 5, or 9 blisters in a cardboard bundle.
Category home away from home
Group rate of Industria Chemist e Farmaceutica S. p. A./
Recordati Industria Chimica e Farmaceutica SpA
Manufacturer's location and address of the place of business
Via M. Civitali 1, 20148, Milan, Italy/
Via M. Civitali 1, 20148 Milan, Italy.
Group Rate Ailand Ltd/
Recordati Ireland Ltd.
The location of the applicant
Regins East, Ringaskiddy, Ko. Cork, Ireland/
Raheens East, Ringaskiddy, Co. Cork, Ireland.
HAVE UROREC HARD CAPSULES 4MG
Urorec was part of a group of antagonists of alpha-adrenergic receptors containing the active substance silodosin. The drug is released in the form of solid capsules of gelatin, with a content of 4 milligrams of silodosin in each. In a package of 3 blisters, each 10 capsules.
Effect on the body, indications
Silodosin acts as a substance with a high selective effect. It is the antagonist of alpha1-adrenoreceptors located in the prostate, the bladder (at the bottom and in the neck), as well as in the prostate region of the urethra. Due to the blockade of these recipes there is a relaxation of smooth tissues of these departments, so the outflow of urine becomes better. During the administration of the drug eliminates irritation and obstruction caused by BPH.
Features of the tool:
The drug is indicated for the symptomatic treatment of BPH.
It is not recommended to take the medicine with high sensitivity to the elements of the composition (active or auxiliary).
Intake and dosage
Uretek consumed orally. The normal daily dose is two capsules 1 time/day with a possible decrease in dosage if necessary.
The medicine is taken during a meal. Swallow the capsule whole with some liquid. During therapy, it is recommended to observe the regimen of administration, namely the same time of use.