Урсолив

General characteristics. Structure:

Active agent: ursodezoksikholevy acid of 250 mg

Excipients: lactulose, cellulose microcrystallic, povidone low-molecular, magnesium stearate, talc.

Structure of the capsule: gelatin, titanium dioxide, dye azoruby.

Pharmacological properties:

Drug renders hepatoprotective, cholagogue, cholelitholytic, hypolipidemic, gipokholesterinemichesky and some immunomodulatory action.
In the researches in vitro it is shown that ursodezoksikholevy acid (UDHK) has direct tire-tread effect on cells of a liver and reduces a hepatotoxic of hydrophobic salts of bile acids.
The main effects of UDHK on exchange of cholesterol include: decrease in secretion of cholesterol, reduction of its intestinal absorption and stimulation of an exit of cholesterol from cholesteric stones in bile. UDHK, braking GMK-KOA-reduktazu, renders also moderate overwhelming effect on synthesis of cholesterol in a liver, increases solubility of cholesterol in bile-excreting system. Causes partial or full dissolution of cholesteric gallstones at enteral use, reduces a bile saturation cholesterol. Stimulates education and biliation, accelerates removal of toxic bile acids through intestines.
At oral administration UDHK share in a common pool of bile acids considerably increases. UDHK competes with other bile acids in the course of absorption in a small bowel, and also at penetration through a hepatocyte membrane that leads to reduction of absorption of toxic bile acids in intestines and receipts them in a liver, preventing their cytopathic action. Reduces a bile litogennost, increases in it concentration of bile acids, causes strengthening of gastric and pancreatic secretion, increases activity of a lipase, has hypoglycemic effect.
Exerts impact on immunological reactions, reducing a pathological expression of antigens of the main complex of histocompatability of HLA І on hepatocytes and HLA II on holangiotsita, suppresses products interleykina-2, reduces quantity of eosinophils.

Pharmacokinetics. Absorption. UDHK is absorbed in a small bowel (about 90%), at this Cmax in a blood plasma at administration of drug inside in a dose of 250 mg makes about 3.3 mkg/ml, Tmax is about 2 h.

Distribution. Linkng with proteins of plasma of not conjugated UDHK at healthy people makes not less than 70%. Gets through a placental barrier. At systematic reception in doses of 13-15 mg/kg / UDHK becomes the main bile acid in serum and makes from 30 to 50% of the general content of bile acids in blood. The therapeutic effect of drug depends on concentration of UDHK in bile.

Metabolism and removal. It is metabolized in a liver with transformation into taurinovy and glycine conjugates which cosecrete in bile. About 50-70% of the dose of drug accepted inside are removed with bile. Removal with urine does not exceed 1%. The insignificant quantity of UDHK which is not soaked up after oral administration comes to a large intestine where is exposed to splitting by bacteria (7 dehydroxylation); the formed lithocholic acid partially is soaked up from a large intestine, sulphated in a liver and quickly removed in the form of a sulfolitokholilglitsinovy or sulfolitokholiltaurinovy conjugate.

Indications to use:

— primary biliary cirrhosis in the absence of decompensation signs (symptomatic therapy);
— dissolution of small and average cholesteric stones at the functioning gall bladder;
— biliary reflux gastritis.

Route of administration and doses:

Drug is appointed inside.
At dissolution of cholesteric gallstones of the capsule accept in the evening, before going to bed, without chewing and washing down with a small amount of liquid.
Dose of 10 mg/kg of body weight daily that corresponds:
To 2 capsules of the drug Ursoliv® at patients with body weight to 60 kg;
To 3 capsules - at patients with body weight to 80 kg;
To 4 capsules - at patients with body weight to 100 kg;
To 5 capsules - patients with body weight have over 100 kg.
Treatment duration - 6-12 months.
For prevention of repeated formation of stones administration of drug within several more months after dissolution of stones is recommended.
At a symptomatic treatment of primary biliary cirrhosis the daily dose depends on body weight and makes from 2 to 6 capsules (from 10 to 15 mg/kg of body weight).
Drug is accepted with food, washing down with enough water.

The following mode of use is recommended:

Body weight	Daily dose	In the morning	In the afternoon	In the evening
34-50 kg	2 capsules	1	-	1
51-65 kg	3 capsules	1	1	1
66-85 kg	4 capsules	1	1	2
86-110 kg	5 capsules	1	2	2
More than 110 kg	6 capsules	2	2	2

For treatment biliary the reflux gastritis is appointed on 1 capsule of 1 time/days before going to bed. A course of treatment - from 10-14 days to 6 months, if necessary - up to 2 years.

Features of use:

For dissolution of gallstones of UDHK concrements have to be cholesteric (not X-ray contrast), no more than 15-20 mm in size. At the same time the gall bladder has to remain functional, and passability vesical and the general bilious channels has to be kept.

At appointment for the purpose of dissolution of gallstones it is necessary monthly, and then - each 3 months to carry out biochemical analysis of blood for definition of activity of hepatic transaminases, ShchF, GGT, and also concentration of bilirubin. At preservation of the raised indicators drug should be cancelled.

For control of efficiency of treatment it is recommended to spend each 6 months radiological and ultrasound examination of biliary tract.

At calcification of gallstones, disturbance of sokratitelny ability of a gall bladder or frequent attacks of bilious colic treatment should be stopped. If within 6-12 months after the beginning of therapy of partial dissolution of concrements did not occur, it is improbable that treatment will be effective. Detection during treatment of not visualized gall bladder is the certificate that full dissolution of concrements did not happen, and treatment should be stopped.

After full dissolution of stones, for an exception of a recurrence, it is recommended to continue use of UDHK, within 3 months.

Influence on ability to driving of motor transport and to control of mechanisms
Drug does not exert a negative impact on ability to manage vehicles, and/or other mechanisms.

Side effects:

From the alimentary system: nausea, vomiting, pain in epigastric area and the right hypochondrium, a lock, tranzitorny increase in activity of hepatic transaminases; seldom - diarrhea (can be dozozavisimy), calcination of gallstones.
At treatment of primary biliary cirrhosis the passing decompensation of cirrhosis which disappears after drug withdrawal can be observed.
From TsNS: headache, dizziness.
Allergic reactions: skin itch, small tortoiseshell, Quincke's disease.
Others: an indisposition, a mialgiya, an exacerbation of earlier being available psoriasis, an alopecia.

Interaction with other medicines:

At combined use the antacids containing aluminum, and ion-exchange resins (Colestyraminum) reduce absorption of UDHK.

At simultaneous use hypolipidemic medicines (especially Clofibratum), are oestrogenic, Neomycinum or progestogens (oral contraceptives) increase bile saturation by cholesterol and can reduce ability of ursodezoksikholevy acid to dissolve cholesteric gallstones.

At simultaneous use of UDHK can increase cyclosporine absorption.

Contraindications:

— the size of cholesteric stones in a gall bladder more than 20 mm;
— existence X-ray contrast (with the high content of calcium) stones of a gall bladder and the general bilious channel;
— an atrophy of a gall bladder at cholelithiasis, a nonfunctioning gall bladder;
— obstruction of biliary tract;
— acute inflammatory diseases of a gall bladder, bilious channels and intestines;
— cirrhosis in a decompensation stage;
— the expressed liver failure;
— the expressed renal failure;
— pancreatitis (active phase);
— pregnancy;
— lactation period;
— adults and children with body weight to 34 kg (for this dosage form);
— hypersensitivity to drug components.

Use of the drug URSOLIV® at pregnancy and feeding by a breast
Drug is contraindicated at pregnancy and during breastfeeding.

Use at abnormal liver functions
Contraindication: the expressed liver failure.

Use at renal failures
Contraindication: the expressed renal failure.

Use for children
Contraindication: children with body weight to 34 kg (for this dosage form).

Overdose:

Cases of overdose of UDHK are not described so far.

Storage conditions:

Drug should be stored in the unavailable to children, dry, protected from light place at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Капс. 250 mg: 10, 20, 30, 50 or 100 pieces.