Urcevel capsules 250mg, 100pcs

Composition

Per capsule:

Active ingredient: ursodeoxycholic acid – 250.0 mg.

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

Gelatin capsule composition: titanium dioxide, gelatin.

Pharmacological action

Pharmacotherapeutic group: hepatoprotective agent

ATX code: A 05 AA 02

Pharmacological properties

Pharmacodynamics

Hepatoprotective agent, has a choleretic effect. Reduces the synthesis of cholesterol in the liver, its absorption in the intestines and concentration in bile, increases the solubility of cholesterol in the biliary system, stimulates the formation and excretion of bile. Reduces the lithogenicity of bile, increases the content of bile acids in it; causes increased gastric and pancreatic secretion, increases the activity of lipase, has a hypoglycemic effect. Causes partial or complete dissolution of cholesterol stones with enteral application, reduces the saturation of bile with cholesterol, which contributes to the mobilization of cholesterol from gallstones. It has an immunomodulatory effect, affects immunological reactions in the liver: reduces the expression of certain antigens on the hepatocyte membrane, affects the number of T-lymphocytes, interleukin-2 formation, reduces the number of eosinophils.

Pediatric population

Cystic fibrosis (cystic fibrosis)

According to clinical reports, there is a long-term experience (up to 10 years or more) in the treatment of pediatric patients suffering from cystic fibrosis-related hepatobiliary disease (CFAHD) with ursodeoxycholic acid. There is evidence that ursodeoxycholic acid therapy can reduce the proliferation of bile ducts, slow the development of lesions detected by histological examination, and even contribute to the reverse development of changes in the hepatobiliary system if therapy begins in the early stages of CFAHD. In order to optimize the effectiveness of treatment, ursodeoxycholic acid therapy should be initiated as early as possible after the diagnosis

of CFAHD.

After oral use, 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 dose is absorbed. After absorption, ursodeoxycholic acid is almost completely conjugated in the liver with glycine and taurine and is excreted in the bile. At the first passage through the liver, up to 60% is metabolized.

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 the content of other, more lipophilic bile acids.

Under the action of intestinal bacteria, ursodeoxycholic acid partially decomposes to form 7-keto-litocholic and litocholic acid. Litocholic acid is hepatotoxic; in some animal species, it causes damage to the liver parenchyma. In the human body, it is absorbed only in small amounts. In the process of metabolism, it is sulfated in the liver, due to which it is neutralized even before it is excreted into the bile, and is excreted from the body with feces. The half-life of ursodeoxycholic acid is from 3.5 to 5.8 days.

Indications

Dissolution of cholesterol gallstones, biliary reflux gastritis, primary biliary cirrhosis in the absence of signs of decompensation, chronic hepatitis of various origins, primary sclerosing cholangitis, cystic fibrosis, non-alcoholic steatohepatitis, alcoholic liver disease, biliary dyskinesia.

Contraindications

X-ray positive (with high calcium content) gallstones; impaired contractility of the gallbladder, blockage of the biliary tract (blockage of the common bile duct or cystic duct), frequent episodes of biliary colic; acute inflammatory diseases of the gallbladder and bile ducts; cirrhosis of the liver in the decompensation stage; severe hepatic and/or renal failure, hypersensitivity to the components of the drug or other bile acids.

Pediatric population

Unsuccessful portoenterostomy or cases of failure to restore normal bile flow in children with biliary tract atresia.

Ursodeoxycholic acid has no age restrictions on its use, but children under 3 years of age are recommended to use ursodeoxycholic acid in suspension, as it may be difficult to swallow capsules.

Side effects

Classification of the frequency of adverse reactions according to the recommendations of the World Health Organization (WHO): very common ≥ 1/10; often from ≥ 1/100 to < 1/10; infrequently from ≥ 1/1000 to < 1/100; rarely from ≥ 1/10000 to < 1/1000; very rare

Disorders of the gastrointestinal tract

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

Acute pain in the right upper abdomen was very rarely observed in the treatment of primary biliary cirrhosis.

Liver and biliary tract disorders

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

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

Skin and subcutaneous tissue disorders

In very rare cases, allergic reactions may occur, including urticaria.

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

Interaction

Colestyramine, colestipol and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce the 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 may affect the absorption of cyclosporine from the intestine. Therefore, in patients taking cyclosporine, the doctor should check the concentration of cyclosporine in the blood and, if necessary, adjust its dose.

In some cases, ursodeoxycholic acid may reduce the absorption of ciprofloxacin.

In a clinical study involving healthy volunteers, concomitant use of ursodeoxycholic acid (500 mg / day) and rosuvastatin (20 mg/day) resulted in a slight increase in rosuvastatin plasma levels. The clinical significance of this interaction, including with respect to other statins, is unknown. Ursodeoxycholic acid has been shown to reduce peak plasma concentrations (Cmax) and the area under the concentration ‒ time curve (AUC) of the slow calcium channel blocker nitrendipine in healthy volunteers. Careful monitoring is recommended for concomitant use of nitrendipine and ursodeoxycholic acid. You may need to increase the dose of nitrendipine. 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 enzymes of the cytochrome P450-3A system. However, in a planned interaction study with budesonide, which is a known cytochrome P450-3A substrate, induction was not observed.

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

How to take, course of use and dosage

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

Dissolving cholesterol gallstones

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

The drug should be taken daily in the evening, before going to bed (capsules are not chewed), washed down with a small amount of liquid.

The duration of treatment is 6-12 months.  To prevent recurrent cholelithiasis, it is recommended to take the drug for several months after the dissolution of the stones. Treatment of biliary reflux gastritis

1 capsule of ursodeoxycholic acid daily in the evening before going to bed, without chewing and with a small amount of water.

The course of treatment is from 10-14 days to 6 months, if necessary-up to 2 years.

Treatment of primary biliary cirrhosis

The daily dose depends on body weight and ranges from 3 to 7 capsules (approximately 14 ± 2 mg of ursodeoxycholic acid per 1 kg of body weight).

In the first 3 months of treatment, ursodeoxycholic acid should be divided into several doses during the day. After improving liver parameters, the daily dose of the drug can be taken 1 time in the evening.

The following application mode is recommended:

250 mg capsules

Capsules should be taken regularly, without chewing, with a small amount of liquid.

The use of ursodeoxycholic acid for the treatment of primary biliary cirrhosis can be continued indefinitely.

In patients with primary biliary cirrhosis, in rare cases, clinical symptoms may worsen at the beginning of treatment, for example, pruritus may become more frequent. In this case, treatment should be continued, taking 1 capsule daily, then gradually increase the dosage, increasing the daily dose weekly by 1 capsule, until the recommended dosage regimen is reached again.

Symptomatic treatment of chronic hepatitis of various origins – a daily dose of 10-15 mg / kg in 2-3 doses. The duration of treatment is 6-12 months or more.

Primary sclerosing cholangitis ‒ a daily dose of 12-15 mg / kg; if necessary, the dose can be increased to 20-30 mg/kg in 2-3 doses. The duration of therapy is from 6 months to several years (see the section “Special instructions”).

Cystic fibrosis (cystic fibrosis) ‒ a daily dose of 20 mg / kg / day in 2-3 doses, with a further increase to 30 mg/kg/day if necessary.

Non-alcoholic steatohepatitis ‒ an average daily dose of 10-15 mg / kg in 2-3 doses. The duration of therapy is from 6-12 months or more.

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

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

Overdose

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

Description

Solid gelatin capsules No. 0 are white in color. The contents of the capsules are white or almost white powder.

Special instructions

Ursodeoxycholic acid should be administered under medical supervision.

During the first 3 months of treatment, liver function parameters should be monitored: transaminase, alkaline phosphatase, and gamma-glutamyltranspeptidase in the blood serum every 4 weeks, and then every 3 months. Monitoring of these parameters allows detecting liver function disorders in the early stages. This also applies to patients in the late stages of primary biliary cirrhosis. In addition, it can quickly determine whether a patient with primary biliary cirrhosis is responding to treatment.

When used to dissolve cholesterol gallstones

In order to assess progress in treatment and to timely detect signs of calcification of stones, depending on their size, the gallbladder should be visualized (oral cholecystography) with examination of darkening in the 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 stones, weak contractility of the gallbladder or frequent attacks of colic, ursodeoxycholic acid should not be used.

Patients taking ursodeoxycholic acid to dissolve gallstones should use effective non-hormonal methods of contraception, as hormonal contraceptives can increase the formation of gallstones (see the sections “Interaction with other medications” and “Use during pregnancy and lactation”).

In the treatment of patients in the late stages of primary biliary cirrhosis

Cases of decompensation of cirrhosis of the liver were extremely rare. After discontinuation of therapy, there was a partial reversal of decompensation symptoms.

In patients with primary biliary cirrhosis, in rare cases, clinical symptoms may increase at the beginning of treatment, for example, pruritus may increase. 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 can cause serious side effects.

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

Effect on the ability to drive vehicles and mechanisms Ursodeoxycholic acid does not affect the ability to drive vehicles and mechanisms, or this effect is minimal.

Storage conditions

In a place protected from light at a temperature of no more than 25 degrees. Keep out of reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Ursodeoxycholic acid

Conditions of release from pharmacies

By prescription

Dosage form

Capsules