Grinterol, 250 mg capsules 100 pcs

Pharmacodynamics

Hepatoprotective agent, also has choleretic, cholestolytic, hypolipidemic, hypocholesterolemic and some immunomodulatory action.

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

Competitively reduces absorption of lipophilic bile acids in the intestine, increases their “fractional” turnover in enterohepatic circulation, induces choleresis, stimulates bile passage and excretion of toxic bile acids through the intestine. It shields non-polar bile acids (chenodeoxycholic acid), due to which mixed (non-toxic) micelles are formed.

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

Enhances the solubility of cholesterol in the biliary system, stimulates the formation and excretion of bile. It decreases lithogenicity of bile, increases concentration of bile acids in it; it causes intensification of gastric and pancreatic secretion, increases lipase activity and has hypoglycemic effect. Causes partial or complete dissolution of cholesterol gallstones when administered orally, reduces the saturation of bile with cholesterol, which promotes its mobilization from the gallstones.

It has immunomodulatory effect, influences immunological reactions in the liver: it decreases the expression of some histocompatibility antigens – HLA-1 on membrane of hepatocytes and HLA-2 on cholangiocytes, affects the number of T-lymphocytes, interleukin 2 formation, decreases the number of eosinophils, suppresses immunocompetent Ig (first of all IgM).

Pharmacokinetics

Absorption from the small intestine is high (about 90%). It penetrates through the placental barrier. Cmax in oral administration of 50 mg in 30, 60, 90 minutes is 3.8; 5.5; 3.7 mmol/l, respectively. ÒCmax is 1-3 hours. The binding to plasma proteins is high.

Metabolized in the liver (clearance during “primary passage” through the liver) to taurine and glycine conjugates, which are secreted into the bile. The excretion is 50? 70% via the intestine. A small amount of unabsorbed 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 rapidly excreted as a sulfolithocholylglycine or sulfolithocholyltaurine conjugate.

Indications

The 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),

– non-alcoholic steatohepatitis,

– alcoholic liver disease (ALD),

– biliary dyskinesia.

Active ingredient

Composition

One capsule contains:

active ingredient:

ursodeoxycholic acid – 250.0 mg;

excipients:

corn starch – 73.0 mg,

silicon dioxide – 5.0 mg,

How to take, the dosage

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

The dissolution of cholesterol gallstones: 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. To prevent recurrent stone formation it is recommended to continue taking the drug for several months after the stones have dissolved.

The 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 (up to 20 mg/kg if necessary) per day in 2?3 intakes during the first 3 months of treatment. After improvement of hepatic indices the daily dose can be administered once in the evening.

The following regimen is recommended:

Body weight

(kg)

Daily dose

(number of capsules)

In the morning

During the day

p> In the evening

47-62

3

1

1

/p>

1

63-78

4

1

1

2

79-93

5

1

2

p> 2

94-109

6

2

2

p> 2

Above 100

7

2

2

3

The duration of treatment is not limited. In rare cases, at the beginning of treatment, clinical symptoms may worsen (increased itching). If this occurs, use 1 capsule daily; then the dosage should be gradually increased (increasing the daily dose by 1 capsule weekly) until the recommended dosage regimen is reached.

The symptomatic treatment of chronic hepatitis of different genesis: daily dose is 10-15 mg/kg in 2-3 doses. 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 doses. Duration of use – from 6 months to several years.

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

Non-alcoholic steatohepatitis: average daily dose is 10-15 mg/kg in 2?3 doses. Duration of use – from 6-12 months and longer.

Children over 3 years of age are prescribed individually at the rate of 10-20 mg/kg per day.

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

Biliary dyskinesia: average daily dose is 10 mg/kg in 2 doses for 2 weeks to 2 months. It is recommended to repeat the treatment course if necessary.

Children and adults with body weight less than 47 kg are recommended to use the drug in suspension of other manufacturers.

Interaction

Antacids containing aluminum hydroxide, aluminum oxide and ion exchange resins (colestyramine, colestipol) reduce absorption of ursodeoxycholic acid in the intestine, thus reducing its effectiveness; therefore, these drugs should be used 2 hours before taking ursodeoxycholic acid.

Ursodeoxycholic acid may enhance intestinal absorption of cyclosporine; therefore, the dose of cyclosporine should be adjusted if used concomitantly.

Ursodeoxycholic acid may decrease absorption of ciprofloxacin.

Hypolipidemic drugs (especially clofibrate), estrogens, neomycin or progestins, and oral contraceptives increase bile cholesterol saturation and may decrease the ability to dissolve cholesterol-containing bile concretions.

Special Instructions

The treatment should be carried out under the supervision of a physician.

When prescribing for dissolution of gallstones it is necessary to monitor the activity of “hepatic” transaminases and chelonic phosphatase, gamma-glutamyl transpeptidase, bilirubin concentration. Cholecystography should be performed every 4 weeks during the first 3 months of treatment, and then – every 3 months. Control of treatment efficacy should be carried out every 6 months by ultrasound investigation (USI) during the first year of therapy.

If elevated values persist, the drug should be discontinued.

For successful dissolution, it is necessary that the stones are pure cholesterol stones not more than 15-20 mm in size, the gallbladder is not more than half filled with stones and the biliary tract completely retains its function.

After complete dissolution of the concrements, it is recommended to continue use for at least 3 months, in order to promote dissolution of the remaining concrements, which are too small to be detected.

If partial dissolution has not occurred within 6 to 12 months of initiating therapy, it is unlikely that treatment will be effective.

The detection of an unvisualized gallbladder during treatment is an indication that complete dissolution of the concrements has not occurred, and treatment should be stopped.

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

Long-term therapy with high doses of ursodeoxycholic acid (28-30 mg/kg/day) may lead to serious adverse events in patients with primary sclerosing cholangitis.

The effect on the ability to drive vehicles, mechanisms:

The effect on the ability to drive vehicles, mechanisms has not been identified.

Contraindications

– Hypersensitivity to the components of the drug;

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

– non-functioning gallbladder;

– acute inflammatory disease of the gallbladder, bile ducts, and intestines;

– decompensated cirrhosis of the liver;

– expressed hepatic and/or renal failure;

– pancreatitis;

– children under 3 years of age (for capsules).

With caution

Children aged 3 to 4 years should use with caution, because it may be difficult to swallow the capsules.

Side effects

Gastrointestinal disorders: loose stools or diarrhea. In treatment of primary biliary cirrhosis, acute pain in the right upper abdomen may be observed.

Liver and biliary tract disorders: calcification of gallstones. During treatment of primary biliary cirrhosis transient decompensation of liver cirrhosis may be observed (passes after discontinuation of the drug).

Skin and subcutaneous tissue disorders: allergic reactions (including urticaria).

Overdose

There are no known cases of ursodeoxycholic acid overdose.

Similarities