Grinterol - instructions for use, dose, side effects, contraindications

It is built into the membrane of the hepatocyte, stabilizes its structure and protects the hepatocyte from damaging effects of bile salts, thus reducing their cytotoxic effect. When cholestasis activates Ca²⁺-dependent alpha protease and stimulates exocytosis, reduces the concentration of toxic bile acids (chenodeoxycholic, lithocholic, deoxycholic, etc.), whose concentrations in patients with chronic liver diseases are increased.

Competitive reduces the absorption of lipophilic bile acids in the intestine, increases their "Fractional" turnover under enterohepatic circulation cholepoiesis induces, promotes the passage of bile and excretion of toxic bile acids across the gut. It screens nonpolar bile acids (chenodeoxycholic), due to which mixed (non-toxic) micelles are formed.

Reduces the saturation of bile with cholesterol by reducing the synthesis and secretion of cholesterol in the liver and inhibiting its absorption in the intestine.

Increases the solubility of cholesterol in the bile excretory system, stimulates the formation and secretion of bile. It reduces the lithogenicity of bile, increases the concentration of bile acids in it, causes an increase in gastric and pancreatic secretion, increases lipase activity, and has a hypoglycemic effect. It causes partial or complete dissolution of cholesterol gallstones when applied orally, reduces the saturation of bile with cholesterol, which contributes to its mobilization from gallstones.

Has an immunomodulatory effect, affects immunological reactions in the liver: reduces the expression of certain histocompatibility antigens - HLA-1 on the membrane of hepatocytes and HLA-2 on cholangiocytes, affects the number of T-lymphocytes, the formation of interleukin 2, reduces the number of eosinophils, suppresses immunocompetent Ig (Firstly IgM).

Pharmacokinetics:

Absorption from the small intestine is high (about 90%). Penetrates through the placental barrier. FROM_m_Oh when administered 50 mg after 30, 60, 90 minutes - 3.8; 5.5; 3.7 mmol / l, respectively. TS_m_Oh - 1-3 hours. The connection with plasma proteins is high.

Metabolised in the liver (clearance during "primary passage" through the liver) into the taurine and glycine conjugates, which are secreted in bile. It is deduced on 50-70% through an intestine. A small amount of unsweetened ursodeoxycholic acid enters the large intestine, where it undergoes cleavage by bacteria (7-dehydroxylation); the resulting lithocholic acid is partially absorbed from the colon but is sulfated in the liver and is rapidly excreted as a sulfolithocholylglycine or sulfolithocholyltaurine conjugate.

Indications:

- Dissolution of small and medium cholesterol stones with a functioning gallbladder,

- biliary reflux-gastritis,

- primary biliary cirrhosis in the absence of signs of decompensation (symptomatic therapy),

- chronic hepatitis of various genesis,

- primary sclerosing cholangitis, cystic fibrosis (cystic fibrosis),

- nonalcoholic steatohepatitis,

- alcoholic liver disease (ABP),

- biliary dyskinesia.

Contraindications:

- Hypersensitivity to the components of the drug;

- X-ray positive (high in Ca²⁺) gallstones;

- non-functioning gallbladder;

- acute inflammatory diseases of the gallbladder, bile ducts and intestines;

- cirrhosis of the liver in the stage of decompensation;

- marked hepatic and / or renal insufficiency;

- pancreatitis;

- children under 3 years (for capsules).

Carefully:

Children aged 3 to 4 years should be used with caution, because it is difficult to swallow capsules.

Pregnancy and lactation:

In animal studies, mutagenic and carcinogenic effects have not been identified, however, due to the lack of clinical studies in pregnant women, use during pregnancy is only possible if the expected benefit to the mother exceeds the potential risk to the fetus.

Data on excretion with breast milk are not available, so if you need to use during lactation, you should stop breastfeeding.

Dosing and Administration:

Inside. Capsules are taken in the evening, without chewing, with a small amount of water.

Dissolution of gallstones cholesterol stones: the average daily dose is 10 mg / kg, which corresponds to:

Body weight (kg)	Number of capsules
Up to 60	2
61-80	3
81-100	4
Over 100	5

The course of treatment is 6-12 months. For the prevention of repeated formation of stones, it is recommended to take the drug for several months after the dissolution of the stones.

Treatment of biliary reflux gastritis: one capsule 250 mg once a day in the evening. The course of treatment - from 10-14 days to 6 months, if necessary - up to 2 years.

Symptomatic treatment of primary biliary cirrhosis in the absence of signs of decompensation: 10-15 mg / kg (if necessary - up to 20 mg / kg) per day in 2-3 doses in the first 3 months of treatment. After improving liver function, the daily dose can be applied once in the evening.

The following application mode is recommended:

Body weight (kg)	Daily dose (number of capsules)	In the morning	In the afternoon	In the evening
47-62	3	1	1	1
63-78	4	1	1	2
79-93	5	1	2	2
94-109	6	2	2	2
Over 100	7	2	2	3

The duration of the course of treatment is not limited. In rare cases, clinical symptoms may worsen at the beginning of treatment (itching may occur). In this case, one capsule should be used daily,then gradually increase the dosage (weekly increasing the daily dose per capsule) until the recommended dosing regimen is reached.

Symptomatic treatment of chronic hepatitis of different genesis: The daily dose is 10-15 mg / kg in 2-3 doses. The duration of treatment is 6-12 months or more. Primary sclerosing cholangitis: 12-15 mg / kg (up to 20 mg / kg) of body weight per day in 2-3 divided doses. Duration of use - from 6 months to several years.

Cystic fibrosis (cystic fibrosis): 20-30 mg / kg per day in 2-3 divided doses. Duration of use - from 6 months to several years.

Nonalcoholic steatohepatitis: the average daily dose is 10-15 mg / kg in 2-3 doses. Duration of use - from 6-12 months or more.

Children aged 3 years appoint individually, at a rate of 10-20 mg / kg per day.

Alcoholic liver disease: the average daily dose is 10-15 mg / kg in 2-3 doses. The duration of therapy is 6-12 months or more.

Biliary dyskinesia: an average daily dose of 10 mg / kg in 2 divided doses for 2 weeks to 2 months. If necessary, the course of treatment is recommended to be repeated.

Children and adults weighing less than 47 kg it is recommended to apply the drug in suspension of other manufacturers.

Side effects:

Disorders from the gastrointestinal tract: unformed stools or diarrhea. In the treatment of primary biliary cirrhosis, acute pain in the right upper abdomen can be observed.

Disorders from the liver and bile ducts: calcification of gallstones. In the treatment of primary biliary cirrhosis, transient decompensation of liver cirrhosis can occur (after the drug is withdrawn).

Disturbances from the skin and subcutaneous tissues: allergic reactions (including urticaria).

Overdose:

Cases of overdose of ursodeoxycholic acid are not known.

Interaction:

Antacids containing aluminum hydroxide, aluminum oxide and ion exchange resins (colestramine, colestipol), reduce the absorption of ursodeoxycholic acid in the intestines, thus reducing its effectiveness; therefore the listed preparations should be applied 2 hours prior to the reception of ursodeoxycholic acid. Ursodeoxycholic acid can enhance the absorption of cyclosporine from the intestine, so with simultaneous use, the dose of cyclosporin should be adjusted. Ursodeoxycholic acid can reduce the absorption of ciprofloxacin.Lipid-lowering drugs (especially clofibrate), estrogens, neomycin or progestins, oral contraceptives increase the saturation of bile with cholesterol and may reduce the ability to dissolve cholesterol bile stones.

Special instructions:

Treatment should be under the supervision of a physician.

When assigning to dissolve gallstones is necessary to monitor the activity of "liver" transaminases and alkaline phosphatases, gamma-glutamyl transpeptidase, bilirubin concentration. Cholecystography should be performed every 4 weeks in the first 3 months of treatment, then every 3 months. Control the effectiveness of treatment every 6 months during ultrasound (ultrasound) during the first year of therapy.

If the increased indices remain, the drug should be discontinued.

To successfully dissolve it is necessary that the stones are pure cholesterol, with a size not exceeding 15-20 mm, the gallbladder is filled with stones no more than half and the bile ducts fully retained their function.

After complete dissolution of the calculus, it is recommended to continue use for at least 3 months,in order to promote the dissolution of stone residues, the dimensions of which are too small for their detection.

If within 6-12 months after the beginning of therapy of partial dissolution of concrements did not occur, it is unlikely that the treatment will be effective.

Detection during treatment of a non-visualizable gallbladder is evidence that no complete dissolution of the calculi has occurred, and treatment should be discontinued.

In patients with diarrhea, the dosage of ursodeoxycholic acid should be reduced. With persistent diarrhea, treatment should be discontinued.

Long-term therapy with high doses of ursodeoxycholic acid (28-30 mg / kg / day) can lead to the development of serious side effects in patients with primary sclerosing cholangitis.

Effect on the ability to drive transp. cf. and fur:

Influence on ability to drive vehicles, mechanisms is not revealed.

Form release / dosage:

Capsules 250 mg.

Packaging:

10 capsules in a contour cell box made of polyvinylchloride film and aluminum foil.

For 5 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002649

Date of registration:08.10.2014 / 11.02.2016

Expiration Date:08.10.2019

The owner of the registration certificate:Grindeks Rus, Open CompanyGrindeks Rus, Open Company Russia

Manufacturer: & nbsp

GRINDEX, AO Latvia

Representation: & nbspGrindeks Rus, Open CompanyGrindeks Rus, Open CompanyRussia

Information update date: & nbsp10.05.2017

Illustrated instructions

Instructions

Grinterol® (Grinterol®)