The instruction for medical use of URSOTSID® medicine Trade name УРСОЦИД® the International unlicensed name Ursodezoksikholevaya acid the Dosage form of the Capsule of 250 mg Structure One capsule contains active agent – ursodezoksikholevy acid of 250 mg, excipients – starch prezhelatinizirovanny, cellulose microcrystalline PH 101, silicon dioxide colloidal (Aerosil 200), magnesium stearate, structure of a cover of the capsule: gelatin, caramel (E150), ferrous oxide red (E172), titan dioxide (E 171). The description Solid gelatin capsules with the transparent light brown body and an opaque lid of red-brown color. Capsule contents – white powder. Pharmacotherapeutic group Drugs for treatment of diseases of a liver and biliary tract. Drugs for treatment of a disease of a gall bladder. Drugs of bile acids. Ursodezoksikholevy acid. The ATX A05AA02 code the Pharmacological Pharmacokinetics Later properties of intake ursodezoksikholevy acid is quickly soaked up in a small intestine due to passive diffusion, and in an ileal gut due to active diffusion. Speed of absorption is 60-80%. Ursodezoksikholevy acid is metabolized mainly in a liver in taurinovy and glycine conjugates and removed in the conjugated form with bile by enterogepatichesky recirculation (50 – 70%) and partially – with excrements. The pharmacodynamics of Ursodezoksikholevaya acid reduces synthesis of cholesterol in a liver, its absorption in intestines and concentration in bile, increases solubility of cholesterol in a bile-excreting system, stimulates education and removal of bile. The therapeutic effectiveness of drug is caused by its ability to normalize holepoetichesky function, to reduce a bile litogennost, to prevent formation of bilious concrements and to promote dissolution of already available cholesteric gallstones. Ursodezoksikholevy acid eliminates the dispeptic symptoms accompanying gepatobiliarny pathologies and is applied in cholestatic diseases of a liver. Indications – for dissolution of cholesteric stones of a gall bladder – a biliary reflux gastritis – the gepato-biliary disturbances connected with a mucoviscidosis at children from 6 to 18 years as a part of complex therapy: – primary biliary cirrhosis in the absence of signs of a decompensation the Route of administration and doses УРСОЦИД® is accepted inside, without chewing and washing down with a small amount of water. To apply regularly. Before use consult with your attending physician. Dissolution of cholesteric gallstones: In a daily dose 10mg/kg body weights daily that corresponds: 2 URSOTsIDa® capsules at patients with body weight to 60 kg to 3 URSOTsIDa® capsules at patients with body weight to 80 kg to 4 URSOTsIDa® capsules at patients with body weight to 100 kg to 5 URSOTsIDa® capsules at patients with body weight need to accept over 100 kg of the Capsule once a day before going to bed. Duration of process of dissolution of gallstones at use of drug is from 6 months to 2 years. If in 12 months from the beginning of use the reduction of gallstones is not observed, then it is inexpedient to continue treatment. Control of efficiency of treatment is exercised by an ultrasonic method of a research or by means of X-ray analyses each 6 months. At the subsequent survey it is necessary to check whether there was no calcification of stones. In case it occurred, treatment has to be stopped. Biliary reflux gastritis: On 1 capsule in the evening before going to bed. The course of treatment makes 10-14 days. In general, duration of use depends on the course of the disease. Primary biliary cirrhosis: The daily dose of drug depends on the body weight of the patient, and varies from 3 to 7 capsules (14±2 mg of ursodezoksikholevy acid on 1 kg of body weight). In the first 3 months of treatment the administration of drug should be divided for day. After improvement of indicators of a liver it is possible to accept a daily dose of drug once, in the evening before going to bed. Body weight (kg) УРСОЦИД®, capsules of 250 mg the First three months further (1raz/put) Morning Midday Evening 47-62 1 1 1 3 63-78 1 1 2 4 79-93 1 2 2 5 94-109 2 2 2 6 Over 100 2 2 3 7 Use of capsules can be continued during unlimited time. At patients with primary biliary cirrhosis in rare instances clinical symptoms can worsen in an initiation of treatment, for example, the itching can become more frequent. In this case treatment should be continued, accepting on one capsule daily, further it is necessary to raise gradually a dosage (increasing a daily dose weekly by one capsule) until again the recommended dosing mode is not reached. Children at the age of 6-18 years the Daily dose depends on body weight and makes 20мг/кг/сутки, with further increase up to 30 mg/kg/days, if necessary. The body weight (kg) the Daily dose (mg/kg) УРСОЦИД®, capsules of 250 mg Morning Put Evening 20 – 29 17-25 1 – 1 30 – 39 19-25 1 1 1 40 – 49 20-25 1 1 2 50 – 59 21-25 1 2 2 60 – 69 22-25 2 2 2 70 – 79 22-25 2 2 3 80 – 89 22-25 2 3 3 90 – 99 23-25 3 3 3 100 – 109 23-25 3 3 4 & gt, 110 3 4 4 Side effects Often (≥1/100, but & lt, 1/10): – a pasty chair – diarrhea Very seldom (& lt, 1/10ˈ000): – severe pains in a stomach, on the right side during treatment of primary biliary cirrhosis – calcination of gallstones – a cirrhosis decompensation, at treatment of late stages of primary biliary cirrhosis which regresses partially after drug withdrawal. – a small tortoiseshell of the Contraindication – hypersensitivity to components of drug or bile acids – acute inflammatory diseases of a gall bladder or bile ducts, an empyema of a gall bladder – impassability of bile ducts (the general bile ducts or vesical channels) – frequent episodes of hepatic gripes – X-ray positive (with the high content of calcium) gallstones – disturbances of contractility of a gall bladder – children with an atresia of biliary tract: unsuccessful porto-enterostomy, normal current of bile is not restored – Medicinal interactions УРСОЦИД® it is not necessary to appoint children’s age up to 6 years along with Colestyraminum, kolestipoly or the antacids containing hydroxide or aluminum oxide as these drugs in intestines connect ursodezoksikholevy acid inhibit its absorption and reduce efficiency of therapy. If necessary these drugs need to be taken, at least, with a 2-hour interval to or after administration of drug. Ursodezoksikholevy acid can increase intestinal absorption of cyclosporine. Therefore when performing such combination therapy it is necessary to control the serumal level of cyclosporine and if necessary to regulate its dose. In some cases ursodezoksikholevy acid can reduce ciprofloxacin absorption. Ursodezoksikholevy acid reduces values of the maximum concentration in blood plasma and values of the area under curve (AUC) of the calcic antagonist of a nitrendipin and also reduces therapeutic effectiveness of dapsone. These data indicate possible induction by ursodezoksikholevy acid cytochrome of P450-dependent enzymes 3A. Estrogen and some hypolipidemic drugs, such as Clofibratum, can promote formation of bilious concrements, reduce efficiency of ursodezoksikholevy acid at dissolution of gallstones. The special indications URSOTSID® of the capsule of 250 mg should be accepted under observation of the doctor. Within the first 3 months of treatment every 4 week it is necessary to control functional parameters of a liver and to determine activity of aspartate aminotransferase (nuclear heating plant), alaninaminotranspherase (ALT) and gamma glutamiltransferazy (GGT), further such tests are recommended to be carried out every 3 month. Such monitoring allows to establish the patients with primary biliary cirrhosis responding to performing therapy and also to carry out early identification of possible deterioration in hepatic function, especially patients with primary biliary cirrhosis in an advanced stage have diseases. For assessment of therapeutic effect and early detection of possible calcination of concrements in 6 months after an initiation of treatment, depending on the size of stones, it is necessary to conduct a research of a general view of a gall bladder (oral cholecystography) and diagnostics of possible occlusion of bile ducts in a standing position and lying on spin (ultrasonic inspection). After full dissolution of stones it is recommended to continue use of drug within 3 months to promote dissolution of the remains of stones which sizes are too small for their detection and for prevention of a recurrence of a lithogenesis. УРСОЦИД® it is not necessary to appoint at impossibility of receiving a holetsistogramma of a gall bladder, in the presence of the calcinated concrements, in disorders of motor activity of a gall bladder or frequent biliary gripes. At use of ursodezoksikholevy acid for treatment of primary biliary cirrhosis in an advanced stage of a disease cirrhosis decompensation cases which partially regressed after drug withdrawal very seldom were observed. In case of development of diarrhea it is necessary to lower a drug dose, and in case of persistent diarrhea the treatment should be stopped. Pregnancy and a lactation of Sufficient data on use of ursodezoksikholevy acid during pregnancy, especially in the first trimester, it is not received. Researches on animals demonstrate teratogenic action at an early stage of pregnancy. УРСОЦИД® it is not necessary to apply during pregnancy without obvious need. Prior to drug treatment it is necessary to exclude pregnancy. Women of childbearing age can appoint drug only at the condition of application of reliable means of contraception – use of non-hormonal contraceptives or the estrogen containing low doses as oral hormonal contraceptives can promote formation of gallstones is recommended. Data on discharge of ursodezoksikholevy acid breast milk are absent now. In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination. The feature of influence on ability to run the vehicle or potentially dangerous mechanisms does not influence. Overdose Symptoms: in case of overdose of drug the development of diarrhea is possible. In general, development of other symptoms of overdose is improbable since at increase in the accepted dose the absorption of ursodezoksikholevy acid decreases and increases its removal with excrements. Treatment: at overdose performing specific therapy is not required, consequences of diarrhea it is necessary to treat symptomatic with completion of volume of liquid and electrolytic balance. The form of release and packing On 5 or 15 capsules place in blister strip packaging from a white opaque film of PVH/PE/PVDH and printing aluminum foil. On 2, 10, 20 (for 5 capsules) or on 2, 4, 6 (for 15 capsules) planimetric packings together with the instruction for medical use in the state and Russian languages place in a pack cardboard with the hologram of manufacturing firm. To Store storage conditions at a temperature not over 25 of 0C, in the dry, protected from light place. To store out of children’s reach! 2 years not to apply a period of storage after an expiration date. Prescription status According to the prescription the Producer/owner of the registration certificate of JSC Nobel Almatinskaya Pharmatsevticheskaya Fabrika Republic of Kazakhstan Almaty, Shevchenko St. 162 E. The address and a contact information (phone, the fax, e-mail) of the organization in the territory of the Republic of Kazakhstan accepting claims (offer) on quality of medicines from consumers and responsible for post-registration observation of safety of medicine: JSC Nobel Almatinskaya Pharmatsevticheskaya Fabrika Republic of Kazakhstan, Almaty, Shevchenko St. 162 E.