Holudeksan

General characteristics. Structure:

Active agent: ursodezoksikholevy acid - 300,0 mg;

Excipients: starch corn (granulated) - 10,364 mg, starch corn - 66,016 mg (including additional 4,00 mg for moisture compensation), silicon dioxide colloid (aerosil 200) - 5,50 mg, magnesium stearate - 2,0 mg, potassium sorbate - 0,34245 mg;
Structure of a gelatin capsule: gelatin - 96,254 mg, titanium dioxide - 1,585 mg, dye an azoruby - 0,116 mg, dye crimson [Ponso 4R] (only for a lid) - 0,044 mg.

Pharmacological properties:

Pharmacodynamics. Holudeksan - hepatoprotective means, renders also cholagogue, cholelitholytic, hypolipidemic, gipokholesterinemichesky and some immunomodulatory action.
Having high polar properties, ursodezoksikholevy acid (UDHK) forms the non-toxic mixed micelles with non-polar (toxic) bile acids that reduces ability of a gastric reflyuktat to damage cellular membranes at biliary a reflux gastritis and a reflux esophagitis. Besides, UDHK forms the double molecules capable to be included cellular membranes (hepatocytes, holangiotsit, epithelial cells of a GIT (digestive tract)), to stabilize them and to do unreceptive to action of cytotoxic micelles. Reducing concentration of bile acids, toxic for a hepatic cell, and stimulating the cholepoiesis rich with bicarbonates, UDHK effectively promotes permission of an intra hepatic cholestasia. Reduces a bile saturation cholesterol due to oppression of absorption by it in intestines, suppression of synthesis in a liver and decreases in secretion in bile; increases solubility of cholesterol in bile, forming with it liquid crystals; reduces a litogenny index of bile. Dissolution of cholesteric gallstones and the prevention of formation of new concrements is result. The immunopromoting effect is caused by oppression of an expression of HLA-1 antigens on membranes of hepatocytes and HLA-2 on holangiotsita, normalization of a natural killerny lymphocyte activity, etc. Authentically progressing of fibrosis at patients with primary biliary cirrhosis, a mucoviscidosis and alcoholic steatogepatit detains; reduces risk of development of a varicosity of a gullet. UDHK slows down processes of a senilism and death of cells (hepatocytes, holangnotsit, etc.).

Pharmacokinetics. UDHK is absorbed in a small bowel due to passive diffusion (about 90%), and in an ileal gut by means of active transport. The maximum concentration in a blood plasma (Cmax) at intake of 50 mg in 30, 60, 90 min. - 3,8 mmol/l, 5,5 mmol/l and 3,7 mmol/l respectively. Cmax is reached in 1-3 h. Communication with proteins high - to 96-99%. Gets through a placental barrier. At systematic reception of Holudeksan of UDHK becomes the main bile acid in blood serum and makes about 48% of total quantity of bile acids in blood. The therapeutic effect of drug depends on concentration of UDHK in bile.
It is metabolized in a liver (clearance at primary passing through a liver) in taurinovy and glycine conjugates. The formed conjugates cosecrete in bile. About 50-70% of the general dose of drug are removed by bile. The insignificant quantity of not soaked up UDHK 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, but sulphated in a liver and quickly removed in the form of a sulfolitokholilglitsinovy or sulfolitokholiltaurinovy conjugate.

Indications to use:

Uncomplicated cholelithiasis (biliary сладж; dissolution of cholesteric gallstones in a gall bladder at impossibility of their removal surgical or endoscopic by methods; prevention of a recurrence of a lithogenesis after a cholecystectomia).

- Chronic active hepatitis
- Toxic (including medicinal) damages of a liver
- Alcoholic Liver Disease (ALD)
- Not alcoholic steatogepatit
- Primary biliary cirrhosis
- Primary sclerosing holazhit
- Mucoviscidosis
- Atresia of intra hepatic bilious ways, inborn atresia of a bilious channel
- Dyskinesia of biliary tract
- Biliary reflux gastritis and reflux esophagitis.

Route of administration and doses:

Holudeksan accept inside, washing down with enough water, at biliary a reflux gastritis and a reflux esophagitis of-1 times a day, before going to bed, at diffusion diseases of a liver - 2-3 times a day together with the ode.
Chronic diseases of a liver, cholelithiasis (cholesteric gallstones and biliary сладж) - continuously for a long time (from several months to several years) in a daily dose - from 10 mg/kg to 12-15 mg/kg (2-5 capsules). Reception duration for dissolution of stones - before full dissolution plus 3 more months for prevention of a recurrence of a lithogenesis.
At biliary a reflux gastritis and a reflux esophagitis - on 300 mg (1 capsule) a day, before going to bed. A course of treatment - from 10-14 days to 6 months, if necessary - up to 2 years.
After a holetsistekgomiya, for prevention of a repeated cholelithiasis - 300 mg 2 times a day within several months.
Toxic, medicinal damages of a liver, ABP and atresia of bilious ways of-10-15 mg/kg/days within 6-12 months and more. Primary biliary cirrhosis - 10-15 mg/kg/days (if necessary - to 20 mg/kg) from 6 months to several years.
Primary sclerosing cholangitis of-12-15 mg/kg/days (to 20 mg/kg) from 6 months to several years.
Not alcoholic steatogepatit-13-15 mg/kg/days from 6 months to several years.
Mucoviscidosis - 20-30 mg/kg/days (to 20 mg/kg) from 6 months to several years.
To children is more senior than 3 years of UDHK appoint individually, at the rate of 10-20 mg/kg/days.

Features of use:

At administration of drug for the purpose of dissolution of gallstones observance of the following conditions is necessary: stones have to be cholesteric (X-ray negative), their size should not exceed 15-20 mm, the gall bladder has to remain functional and has to be filled with stones no more than half, passability of a vesical and general bilious channel has to be kept. At long (more than 1 month) administration of drug each 4 weeks in the first 3 months of treatment, further - each 3 months to carry out biochemical analysis of blood for definition of activity of "hepatic" transaminases. Control of efficiency of treatment it is necessary to spend each 6 months according to ultrasonic and X-ray inspection of biliary tract.
After full dissolution of stones it is recommended to continue Holudeksan's use within at least 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.
If within 6 months after the beginning of therapy of partial dissolution of stones did not occur, it is improbable that treatment will be effective.

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

Side effects:

Dorsodynia, nausea, vomiting, diarrhea (can be dozozavisimy), locks, passing (tranzitorny) increase in activity of "hepatic" transaminases, allergic reactions, it is rare - calcination of gallstones, an exacerbation of earlier being available psoriasis, an alopecia.

Interaction with other medicines:

The antacids containing aluminum and ion-exchange resins (Colestyraminum) reduce drug absorption. Hypolipidemic medicines (especially Clofibratum), are oestrogenic, Neomycinum or progestins increase bile saturation by cholesterol and can reduce ability to dissolve cholesteric bilious concrements. Increases effect of peroral hypoglycemic drugs.

Contraindications:

Giperchuvstvitepnost to drug, rentgenpolozhitelny (with the high content of calcium) gallstones, a nonfunctioning gall bladder, bilious and gastric fistula, acute cholecystitis, an acute cholangitis, cirrhosis in decompensation stages, acute infectious diseases of a gall bladder, bilious channels and intestines, the expressed liver and/or renal failure, obturation of biliary tract, an empyema of a gall bladder, children's age up to 3 years.

With care
Though UDHK has no age restrictions in use, with care use capsules Holudeksan at children aged from the 3rd up to 4 years since difficulty at a proglatyvaniye of capsules is possible.

Pregnancy and period of a lactation
To women of childbearing age during use of drug recommend to apply non-hormonal contraceptives. Use of UDHK at pregnancy is possible only in that case when the expected advantage for mother exceeds potential risk for a fruit (adequate strictly controlled researches of use of UDHK for pregnant women were not conducted). Data on allocation of UDHK with breast milk are absent now. In need of use of UDHK in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Use in pediatrics
As difficulty at a proglatyvaniye of capsules is possible, drug should not be used in this dosage form at children under 3 years; at children aged from the 3rd up to 4 years it is applied with care.

Overdose:

Cases of overdose of UDHK are not known.

Storage conditions:

To store at a temperature from 15 to 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Capsules of 300 mg.
10 capsules in the blister from aluminum foil and a polyvinyl chloride film.
2 blisters place in a cardboard pack together with the application instruction.