Ursaklin

General characteristics. Structure:

Active ingredient: 250 mg of ursodeoksikholevy acid.

Excipients: starch corn, starch corn prezhelatinizirovanny, silicon dioxide colloid anhydrous, magnesium stearate.

Capsule cover: gelatin, titanium dioxide (Е 171).

Hepatoprotective means, renders also cholagogue, cholelitholytic, hypolipidemic, gipokholesterinemichesky and immunomodulatory action.

Pharmacological properties:

Pharmacodynamics. Ursodeoksikholevy acid (UDHK) represents the tertiary, hydrophilic, not having cytotoxicity bile acid.

UDHK is built in a hepatocyte membrane, stabilizes its structure and protects a hepatocyte from the damaging effect of salts of bile acids, reducing their cytotoxic effect. At a cholestasia activates Ca2+-dependent alpha protease and stimulates an exocytosis, reduces concentration of toxic bile acids (chenodesoxycholic, lithocholic, deoxycholic, etc.) which concentration at patients with chronic diseases of a liver are increased.

Competitively reduces absorption of lipophilic bile acids in intestines, induces a cholepoiesis, stimulates a passage of bile and removal of toxic bile acids through intestines. Shields unpolar bile acids (chenodesoxycholic) thanks to what the mixed (non-toxic) micelles form. It reduces ability of a gastric reflyuktat to damage cellular membranes at gastritis with a gastroduodenal reflux. Besides, UDHK forms the double molecules capable to be included cellular membranes (hepatocytes, holangiotsit, GIT epithelial cells), to stabilize them and to do unreceptive to action of cytotoxic micelles — the cytoprotective, gepatoprotektivny effect.

Reduces bile saturation by cholesterol by reduction of synthesis and secretion of cholesterol in a liver and inhibition of its absorption in intestines. Forms liquid crystals with cholesterol molecules, reducing a bile litogennost, a holato-cholesteric index; promotes dissolution of cholesteric gallstones and prevents formation of new crystals – litolitichesky effect.

Has immunomodulatory effect, influences immunological reactions in a liver: reduces an expression of some histocompatibility antigens - HLA-1 on a membrane of hepatocytes and HLA-2 on holangiotsita, reduces formation of cytotoxic T lymphocytes, reduces quantity of eosinophils, suppresses immunocompetent Ig (first of all IgM).

Authentically progressing of fibrosis at patients with primary biliary cirrhosis, a mucoviscidosis and alcoholic steatogepatit – antifibrolitichesky effect detains.

Pharmacokinetics. Absorption. At oral administration of UDHK it is absorbed in a jejunum due to passive diffusion, and in an ileal gut – by means of active transport. Level of absorption makes 60-80%. The maximum concentration in plasma is reached in 1-3 hours after reception.

Distribution. Linkng with proteins of a blood plasma high - to 96-99%. At systematic reception acid ursodeoksikholevy becomes the main bile acid of blood serum and makes about 48% of total quantity of bile acids in blood. The therapeutic effect depends on concentration of UDHK in bile; against the background of therapy there is a dozozavisimy increase in its share in a bullet of bile acids up to 50-75% (at daily doses of 10-20 mg/kg). Ursodeoksikholevy acid gets through a placental barrier.

Metabolism. About 50-75% of the dose of drug which came to an organism are exposed to "effect of the first passing" through a liver on system of a portal vein. In a liver of UDHK contacts glycine and taurine; the formed conjugates cosecrete in bile. The insignificant quantity of not soaked up UDHK in a large intestine is exposed to splitting by bacteria (7 dehydroxylation) to lithocholic acid which is partially soaked up from a large intestine, is sulphated in a liver and quickly removed with excrements in the form of sulfolitokholilglitsinovy or sulfolitokholiltaurinovy conjugates.

Removal. About 50-70% of a dose are removed with bile, very small quantity (less than 1%) - with urine. T1/2 of ursodeoksikholevy acid makes 3,5-5,8 days.

Indications to use:

- patients with high risk factor of carrying out operation and at patients have a dissolution of cholesteric stones of a gall bladder after a lithotripsy. A condition of success of treatment is normally functioning gall bladder and presence of the pure, seen on x-ray films cholesteric stones which diameter does not exceed 1,5 cm;
- primary biliary cirrhosis of I and II stages;
- primary sclerosing cholangitis;
- hepatitis of various etiology with a cholestatic syndrome;
- reactive gastritis with a gastroduodenal reflux.

Route of administration and doses:

Capsules Ursaklin accept inside, swallowing entirely, not chewing, irrespective of meal and washing down with enough water. Drug is accepted once a day before going to bed or two - three times a day. The mode of dosing and duration of treatment are established individually and weights of a condition of the patient depend on indications.

For various indications the following daily modes of dosing are recommended for use:
• For dissolution of cholesteric gallstones. The usual dose from 2nd to 5 capsules a day, depending on the body weight of the patient (10 mg/kg/days) is recommended. For convenience of dosing it is possible to use the following data:

Body weight	UDHK dose	Number of capsules
to 60 kg to 80 kg to 100 kg over 100 kg	500 mg 750 mg 1000 mg 1250 mg	2 3 4 5

Duration of treatment and its efficiency depends on the size of stones and usually makes 6-12 months. If the size of stones after 12 months does not decrease, then treatment is not recommended to be continued. It is necessary to control success of treatment by means of ultrasonic or radiological researches each 6 months. After dissolution of stones it is reasonable to continue treatment within the next 3 months for the purpose of ensuring full dissolution of concrements.

• For treatment of primary biliary cirrhosis of I and II. Drug is appointed at the rate of 10-15 mg/kg/days (2-6 capsules) in 2-3 receptions. Duration of therapy makes from 6 months to several years.
• For treatment of primary sclerosing cholangitis. The recommended dose makes 12-15 mg/kg/days (to 20 mg) in 2-3 receptions. Duration of therapy makes from 6 months to several years.
• For treatment of hepatitis. Drug appoint in a daily dose 10 mg/kg in 2-3 receptions. Duration of therapy makes from 6 months to several years.
• For treatment of reactive gastritis with a gastroduodenal reflux. Drug is appointed on 250 mg (1 capsule) a day. A course of treatment - 10-14 days (if necessary - up to 2 years).
• For children over 6 years dosing individual at the rate of 10-20 mg/kg/days.

Features of use:

Drug use Ursaklin at cholelithiasis is effective only in the presence of cholesteric (X-ray negative) gallstones no more than 15-20 mm in size, at the kept function of a gall bladder and its fullness stones no more than on a half, at the kept passability vesical and the general bilious channels.

Control of efficiency of treatment is exercised each 6 months by carrying out radiological and ultrasound examination of biliary tract for the purpose of prevention of a recurrence of a cholelithiasis.

At long (more than 1 month) Ursaklin's reception each 4 weeks in the first 3 months of treatment, further - each 3 months it is necessary to carry out biochemical analysis of blood for definition of activity of hepatic transaminases, an alkaline phosphatase, gamma глутамилтрансферазы and bilirubin. At preservation of the raised indicators administration of drug should be cancelled.

After full dissolution of concrements it is recommended to continue treatment within, at least, 3 months, for dissolution of the remains of concrements which sizes are too small for their detection.

Drug is not recommended to be used in cases if the gall bladder cannot be visualized on x-ray films or in cases of calcification of stones, weak contractility of a gall bladder or frequent attacks of biliary gripes.

In spite of the fact that Ursaklin has no age restrictions in use, to children under 6 years drug is not appointed because of possible difficulties at a proglatyvaniye of capsules.

During treatment of the woman of childbearing age have to apply non-hormonal methods of contraception or contraceptives with the low content of estrogen.

Use at pregnancy and in the period of a lactation. Ursaklin's use by women during pregnancy perhaps only in that case when the expected advantage for mother exceeds potential risk for a fruit. The decision on Ursaklin's use is made by the attending physician.

Data on release of ursodeoksikholevy acid with breast milk are absent now. In need of purpose of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Influence on ability to drive the car and potentially dangerous mechanisms. Does not exert impact on ability of control of vehicles or mechanisms.

Side effects:

Ursaklin is rather well had by patients.
Frequency of side effects: very often (> 1/10); often (> 1/100, but <1/10); infrequently (> 1/1000, but <1/100); seldom (> 1/10000, but <1/1000), it is very rare (<1/10000). At use of ursodeoksikholevy acid the following side effects are possible:

Disturbances from digestive tract: often – diarrhea, dyspepsia, it is rare - pain in epigastric area and the right hypochondrium.

Disturbances from a liver and biliary tract: very seldom - calcination of stones, a cirrhosis decompensation which disappears after drug withdrawal.

Hypersensitivity reactions: very seldom – an itch, allergic rash (urticaria).

At treatment of primary biliary cirrhosis the passing decompensation of cirrhosis which disappears after drug withdrawal can be observed.

In case of any unusual reactions it is necessary to stop administration of drug and to consult with the doctor.

Interaction with other medicines:

Colestyraminum, колестипол and the antacids containing aluminum hydroxide connect ursodeoksikholevy acid in intestines, reduce its absorption and weaken efficiency. In case of need simultaneous treatment above-mentioned drugs recommend to apply them in 2 hours prior to or after Ursaklin's reception.

Hypolipidemic medicines (especially Clofibratum), are oestrogenic, Neomycinum, progestins can increase bile saturation by cholesterol and reduce ability of acid ursodeoksikholevy to dissolve cholesteric bilious concrements.

Drug can increase absorption of cyclosporine in intestines. Therefore at the patients who are at the same time accepting this drug it is necessary to control the level of cyclosporine and to adjust its doses.

Peroral contraceptives, estrogen or diet with the low content of cellulose and big the content of cholesterol reduce perspective of success of treatment.

Contraindications:

- hypersensitivity to the active agent or other ingredients which are a part of this medicine;
- rentgenpolozhitelny (with the high content of calcium) gallstones;
- nonfunctioning gall bladder;
- acute inflammatory diseases of a gall bladder, bilious channels and intestines;
- cirrhosis in a decompensation stage;
- the expressed liver and/or renal failure;
- pancreatitis;
- first trimester of pregnancy;
- lactation period;
- the children's age is younger than 6 years.

Overdose:

Overdose symptoms are not known for ursodeoksikholevy acid. Absorption of ursodeoksikholevy acid decreases in process of increase in a dose. In case of developing of diarrhea it is necessary to reduce a dose if diarrhea proceeds, treatment has to be stopped. At use of supermeasured number of capsules the gastric lavage, if necessary - performing symptomatic therapy is recommended.

Storage conditions:

In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

Solid gelatin capsules on 250 mg. 14 capsules in a blister strip packaging. On 2 or 4 blister strip packagings with the instruction on a medical use place in a pack cardboard.