Ursodeoxycholic acid capsules 250mg, 100pcs

Composition

One capsule contains:

Active ingredient: ursodeoxycholic acid-250 mg;

excipients: corn starch-63 mg, povidone K-30-10 mg, colloidal silicon dioxide-5 mg, magnesium stearate-2 mg;

solid gelatin capsules: titanium dioxide-2.0%; gelatin – up to 100%.

Pharmacological action

Pharmacotherapeutic group: Hepatoprotective agent ATX code: A 05 AA 02 Pharmacological Properties Pharmacodynamics

Ursodeoxycholic acid is a hepatoprotective agent that 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. It has a hypoglycemic effect, causes partial or complete dissolution of cholesterol stones when taken orally, 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 in the proximal part of the ileum due to passive diffusion, and in the distal part of the ileum – due to active transport. Approximately 60-80% 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, the type of disease and the state of the liver, 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 influence of intestinal bacteria, ursodeoxycholic acid is partially destroyed with the formation of 7-keto-litocholic and litocholic acids. Litocholic acid is hepatotoxic, and in some animal species it causes damage to the liver parenchyma. In the human body, it is absorbed only in a small amount. 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 excreted through the intestines. The elimination half-life of ursodeoxycholic acid is 3.5-5.8 days.

Indications

-dissolution of cholesterol gallstones;

– biliary reflux gastritis;

– primary biliary cirrhosis of the liver 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.

Use during pregnancy and lactation

Pregnancy

Data on the use of ursodeoxycholic acid during pregnancy are limited or absent. Animal studies have shown the presence of reproductive toxicity at an early stage of pregnancy.

During pregnancy, ursodeoxycholic acid should not be used, except in cases where it is clearly necessary.

Fertility

According to animal studies, ursodeoxycholic acid has no effect on fertility. There are no data on the effect of ursodeoxycholic acid treatment on human fertility.

The use of the drug in women of childbearing age is possible only if reliable methods of contraception are used. It is recommended to use non-hormonal contraceptives, or oral contraceptives with a low content of estrogens. However, patients taking ursodeoxycholic acid to dissolve gallstones should use effective non-hormonal contraceptives, as hormonal oral contraceptives can increase the formation of gallstones. Possible pregnancy should be ruled out before starting treatment.

Breast-feeding

According to several documented cases, the level of ursodeoxycholic acid in breast milk in women is very low, and therefore the occurrence of adverse reactions in children who are breastfed is not expected.

Contraindications

– hypersensitivity to the drug and other bile acids;

– roentgenologically (high in calcium) gallstones;

– violation of the contractility of the gall bladder;

– obstruction of the biliary tract (obstruction 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 stage of decompensation;

– severe hepatic and/or renal failure;

– children’s age up to 3 years (not recommended for use in this dosage form).

Pediatric population

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

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

With caution

Children over 3 years of age (may have difficulty swallowing capsules).

Side effects

Classification of the frequency of side effects according to the recommendations of the World Health Organization (WHO):

very common ≥ 1/10;

common ≥ 1/100 to < 1/10; uncommon ≥ 1/1000 to < 1/100;

rare ≥ 1/10000 to < 1/1000;

very rare < 1/10000, including individual reports;

frequency unknown – it is not possible to determine the frequency of occurrence according to available data.

Gastrointestinal disorders:

often-unformed stools or diarrhea;

very rarely-acute pain in the right upper abdomen (in the treatment of primary biliary cirrhosis).

Liver and biliary tract disorders:

very rarely – calcification of gallstones, decompensation of cirrhosis of the liver, which disappears after discontinuation of the drug (in the treatment of advanced stages of primary biliary cirrhosis).

Skin and subcutaneous tissue disorders:

very rarely – allergic reactions, including urticaria.

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.

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 was shown to reduce the maximum plasma concentration and area under

the concentration-time pharmacokinetic curve 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 P4503a system. However, in a planned interaction study with budesonide, which is a known cytochrome P4503a 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 eliminates the effect of ursodeoxycholic acid, which is used to dissolve gallstones in the gallbladder.

How to take, course of use and dosage

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

Dissolving cholesterol gallstones

The recommended dose of ursodeoxycholic acid depends on body weight and is 10 mg / kg / day (see Table 1).

Table 1 Calculation of the daily number of capsules of the drug depending on body weight

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 the drug daily in the evening, before going to bed (capsules are not chewed), washed down 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 / kg of ursodeoxycholic acid).

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

The following dosage regimen is recommended (Table 2).

Table 2

Mode of use of the drug depending on body weight

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

The use of the drug 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 dose (increasing the daily dose weekly by 1 capsule) until the recommended dosage regimen is reached again.

Symptomatic treatment of chronic hepatitis of various origins

The daily dose is 10-15 mg / kg in 2-3 divided doses. The duration of treatment is 6-12 months or more.

Primary sclerosing cholangitis

The daily dose is 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)

The daily dose is 20 mg / kg / day in 2-3 divided doses, with a further increase to 30 mg/kg/day if necessary.

Table 3

Mode of use of the drug depending on body weight

Non-alcoholic steatohepatitis

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

Alcoholic liver disease

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

Biliary dyskinesia

The average daily dose is 10 mg / kg in 2 divided 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 through the intestine. 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 capsules are a mixture of powder and granules or a compacted mass of white or almost white color.

Special instructions

The drug should be taken under the supervision of a doctor.

During the first 3 months of treatment, liver function parameters should be monitored: transaminase, alkaline phosphatase and gamma-glutamyltranspeptidase in blood plasma 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 using the drug to dissolve cholesterol gallstones

In order to assess progress in treatment and in order to detect signs of calcification of stones in a timely manner, 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, as well as in cases of calcification of stones, weak contractility of the gallbladder or frequent attacks of colic, the drug 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 use”.

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 dose of the drug 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

Store in a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Ursodeoxycholic acid

Conditions of release from pharmacies

By prescription

Dosage form

Capsules