Urcevel, 250 mg capsules 100 pcs

Pharmacotherapeutic group: hepatoprotective agent

ATC code: A05AA02

Pharmacological properties

Pharmacodynamics

Hepatoprotective drug, has choleretic effect. It reduces the synthesis of cholesterol in the liver, its absorption in the intestine and its concentration in bile, increases the solubility of cholesterol in the biliary system, stimulates the formation and excretion of bile. It decreases bile lithogenicity and increases bile acids content; it causes intensification of gastric and pancreatic secretion, increases lipase activity and has hypoglycemic effect. Causes partial or complete dissolution of cholesterol stones in enteral administration, reduces bile saturation with cholesterol, which promotes mobilization of cholesterol from gallstones. It has immunomodulatory effects and influences immunological reactions in the liver: it decreases the expression of some antigens on the membrane of hepatocytes, affects the number of T-lymphocytes, interleukin-2 formation, decreases the number of eosinophils.

Pediatric population

Mucoviscidosis (cystic fibrosis)

. According to clinical reports, there is a long history (up to 10 years or more) of treatment with ursodeoxycholic acid in pediatric patients with hepatobiliary disease associated with cystic fibrosis (CFAHD). There is evidence that therapy with ursodeoxycholic acid can decrease bile duct proliferation, slow down the development of lesions detected by histological examination, and even promote reversal of hepatobiliary changes if therapy is started at early stages of CFAHD. In order to optimize treatment efficacy, ursodeoxycholic acid therapy should be initiated as early as possible after the diagnosis of CFAHD.

Pharmacokinetics

After oral administration, ursodeoxycholic acid is rapidly absorbed in the jejunum and proximal ileum by passive diffusion and in the distal ileum by active transport. Approximately 60-80 % of the administered dose is absorbed. After absorption ursodeoxycholic acid almost completely conjugates in the liver with glycine and taurine and is excreted with bile. During the first passage through the liver it is metabolized up to 60%.

Depending on the daily dose, type of disease and liver condition, more or less ursodeoxycholic acid accumulates in the bile. At the same time, there is a relative decrease in other, more lipophilic bile acids.

In the action of intestinal bacteria ursodeoxycholic acid is partially broken down to form 7-keto-lithocholic acid and lithocholic acid. Lithocholic acid is hepatotoxic; in some animal species it causes damage to the liver parenchyma. In humans it is absorbed only in small amounts. During metabolism it is sulfated in the liver, due to which it is neutralized before it is excreted into bile and excreted with feces. The half-life of ursodeoxycholic acid is from 3.5 to 5.8 days.

Indications

Cholesterol gallstones dissolution, biliary reflux gastritis, primary biliary cirrhosis in the absence of decompensation signs, chronic hepatitis of various genesis, primary sclerosing cholangitis, cystic fibrosis, nonalcoholic steatohepatitis, alcoholic liver disease, biliary dyskinesia.

Active ingredient

Composition

Active ingredient: ursodeoxycholic acid – 250.0 mg.

Excipients: corn starch, colloidal silica (aerosil), magnesium stearate.

Composition of gelatin capsule: titanium dioxide, gelatin.

How to take, the dosage

Children and adults with a body weight less than 47 kg are recommended to use ursodeoxycholic acid in suspension.

Dissolution of cholesterol gallstones

The recommended dose is 10 mg of ursodeoxycholic acid per 1 kg of body weight per day, which corresponds to:

Body weight, kg

2

60-69

22-25

2

70-79

22-25

2

2

3

80-89

22-25

2

3

3

Non-alcoholic steatohepatitis – average daily dose is 10-15 mg/kg in 2-3 doses. The duration of therapy is 6-12 months and longer.

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

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.

Interaction

Colestyramine, colestipol, and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce absorption of ursodeoxycholic acid in the intestine and thus reduce its absorption and effectiveness. If the use of drugs containing at least one of these substances is still necessary, they should be taken at least 2 hours before taking ursodeoxycholic acid.

Ursodeoxycholic acid can affect the absorption of cyclosporine from the intestine. Therefore, in patients taking cyclosporine, the physician should check the blood concentration of cyclosporine and adjust the dose if necessary.

In individual cases ursodeoxycholic acid may decrease absorption of ciprofloxacin.

In a clinical study with healthy volunteers, concomitant use of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) resulted in a slight increase in plasma levels of rosuvastatin. The clinical significance of this interaction, including for other statins, is unknown. In healthy volunteers ursodeoxycholic acid has been shown to decrease peak plasma concentrations (Cmax) and the area under the curve “concentration – time” (AUC) of slow calcium channel blocker – nitrendipine. In case of concomitant use of nitrendipine and ursodeoxycholic acid, close monitoring is recommended. The dose of nitrendipine may need to be increased. There are also reports of interaction with dapsone, which led to a decrease in the therapeutic effect of the latter. These observations, along with data from in vitro experiments, suggest that ursodeoxycholic acid is capable of inducing cytochrome P450 3A enzymes. However, in a planned interaction study with budesonide, which is a known cytochrome P450 3A substrate, no induction was noted.

Estrogenic hormones and blood cholesterol-lowering drugs, such as clofibrate, increase cholesterol secretion in the liver and therefore may stimulate gallstone formation, offsetting the effect of ursodeoxycholic acid, which is used to dissolve gallstones.

Special Instructions

Administration of ursodeoxycholic acid should be under medical supervision.

In the first 3 months of treatment, functional liver parameters: transaminases, alkaline phosphatase and gamma-glutamyl transpeptidase in serum every 4 weeks, and then every 3 months. Monitoring of these parameters allows early detection of liver dysfunction. This also applies to patients in the later stages of primary biliary cirrhosis. In addition, this allows us to quickly determine if a patient with primary biliary cirrhosis is responding to ongoing treatment.

When used to dissolve cholesterol gallstones

In order to evaluate the progress of treatment and for early detection of signs of gallstone calcinosis depending on the gallstone size, the gallbladder must be imaged (oral cholecystography) with observation of darkening in standing and supine positions (ultrasound) 6-10 months after the start of treatment.

If the gallbladder cannot be visualized on X-rays or in cases of calcification of the stones, poor gallbladder contractility or frequent attacks of colic, ursodeoxycholic acid should not be used.

Patients taking ursodeoxycholic acid to dissolve gallstones should use effective non-hormonal contraception, because hormonal contraceptives may increase gallstone formation (see sections “Interaction with other medicinal products” and “Administration during pregnancy and lactation”).

When treating patients in advanced stages of primary biliary cirrhosis

Cases of decompensation of liver cirrhosis were extremely rarely observed. After discontinuation of therapy, a partial reversal of decompensation manifestations was observed.

In patients with primary biliary cirrhosis in rare cases at the beginning of treatment it is possible to increase clinical symptoms, for example, itching may intensify. In this case, the dose of the drug should be reduced, and then gradually increased again, as described in the section “Dosage and administration”.

When used in patients with primary sclerosing cholangitis

Long-term therapy with high doses of ursodeoxycholic acid (28-30 mg/kg/day) in patients with this pathology may cause serious adverse events.

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

The effect on the ability to drive vehicles, mechanisms Ursodeoxycholic acid has no effect on the ability to drive vehicles and mechanisms or this effect is minimal.

Synopsis

Contraindications

Radiopositive (high calcium content) gallstones; impaired gallbladder contractility, biliary tract obstruction (blockage of common bile duct or vesicular duct), frequent episodes of biliary colic; acute inflammatory diseases of gallbladder and bile ducts; decompensated liver cirrhosis; marked liver and/or renal failure, hypersensitivity to the drug components or other bile acids.

Pediatric population

Failure of portoenterostomy or cases of absence of restoration of normal bile flow in children with biliary atresia.

Ursodeoxycholic acid has no age restrictions for use, but in children under 3 years of age, it is recommended that ursodeoxycholic acid be used in suspension, as there may be difficulty in swallowing the capsules.

Side effects

Classification of the incidence of adverse reactions according to the recommendations of the World Health Organization (WHO): very common ≥ 1/10; common ≥ 1/100 to < 1/10; infrequent ≥ 1/1000 to < 1/100; rare ≥ 1/10000 to < 1/1000; very rare < 1/10000, including individual reports; frequency is unknown – based on available data it is impossible to determine the frequency of occurrence.

Gastrointestinal disorders

In clinical studies, loose stools or diarrhea were common during treatment with ursodeoxycholic acid.

In treatment of primary biliary cirrhosis, acute right upper abdominal pain was very rarely observed.

Liver and biliary tract disorders

In very rare cases, calcification of gallstones may occur during treatment with ursodeoxycholic acid.

When treating advanced stages of primary biliary cirrhosis in very rare cases decompensation of liver cirrhosis has been observed, which disappears after discontinuation of the drug.

Skin and subcutaneous tissue disorders

In very rare cases allergic reactions, including urticaria, may be observed.

If any of the side effects listed in the instructions worsen, or if you notice other side effects not listed in the instructions, please tell your doctor.

Overdose

In case of overdose, diarrhea is possible. As a rule, other symptoms of overdose are unlikely, since with increasing dose absorption of ursodeoxycholic acid decreases and, accordingly, more of it is excreted in the feces. There is no need for specific measures in case of overdose. Treatment of the consequences of diarrhea is symptomatic, aimed at replenishment of fluid volume and restoration of electrolyte balance.

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