Instructions for Ursohol capsules 250 mg No. 50
Composition
active ingredient: ursodeoxycholic acid;
1 capsule contains 250 mg of ursodeoxycholic acid;
Excipients: potato starch, methylcellulose, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Capsules.
Main physicochemical properties: hard opaque gelatin capsules with a white cap and body, containing white powder or granules.
Pharmacotherapeutic group
Drugs used in biliary pathology.
ATX code A05A A02.
Drugs used for liver diseases are lipotropic substances.
ATX code A05B.
Pharmacological properties
Pharmacodynamics
Small amounts of ursodeoxycholic acid have been found in human bile. After oral administration, ursodeoxycholic acid reduces the cholesterol saturation of bile by inhibiting its absorption in the intestine and reducing cholesterol secretion into the bile. It is possible that due to the dispersion of cholesterol and the formation of liquid crystals, the gradual dissolution of gallstones occurs.
According to current data, it is believed that the effect of ursodeoxycholic acid in liver diseases and cholestasis is due to the relative replacement of lipophilic, detergent-like toxic bile acids with hydrophilic cytoprotective non-toxic ursodeoxycholic acid, improvement of the secretory capacity of hepatocytes, and immunoregulatory processes.
Use in children
Cystic fibrosis
There is information available from clinical reports regarding the long-term use of ursodeoxycholic acid (up to 10 years) in the treatment of children with hepatobiliary disorders associated with cystic fibrosis. There is evidence that the use of ursodeoxycholic acid can reduce proliferation in the bile ducts, stop the progression of histological changes, and even eliminate hepatobiliary changes if therapy is started in the early stages of cystic fibrosis. For best effectiveness, treatment with ursodeoxycholic acid should be started immediately after the diagnosis of cystic fibrosis is clarified.
Pharmacokinetics
After oral administration, the drug is rapidly and completely absorbed: in the small intestine and upper ileum - by passive transport, and in the terminal ileum - by active transport. Bioavailability is on average 60-80%. The time to reach maximum concentration in blood plasma is 30-60 minutes. Penetrates the placental barrier. Metabolized in the liver by conjugation with the amino acids glycine and taurine. The clearance of the first passage through the liver is up to 60%. Excreted from the body with bile. Depending on the daily dose and the underlying disorder or condition of the liver, the more hydrophilic ursodeoxycholic acid accumulates in bile. At the same time, there is a relative decrease in other more lipophilic bile acids. Under the influence of intestinal bacteria, partial degradation to 7-ketolithocholic and lithocholic acids occurs. Lithocholic acid is hepatotoxic and causes liver parenchymal damage in some animal species. In humans, only a small amount is absorbed, which is sulfated in the liver and thus detoxified before being excreted in the bile and finally in the feces.
The biological half-life of ursodeoxycholic acid is 3.5-5.8 days.
Indication
Dissolution of radiopaque cholesterol gallstones no larger than 15 mm in diameter in patients with a functioning gallbladder, despite the presence of gallstone(s) in it.
Treatment of gastritis with bile reflux.
Symptomatic treatment of primary biliary cirrhosis (PBC) in the absence of decompensated liver cirrhosis.
For the treatment of hepatobiliary disorders in cystic fibrosis in children aged 6 to 18 years.
Contraindication
Hypersensitivity to any substance included in the medicinal product.
Acute inflammation of the gallbladder or bile ducts.
Bile duct obstruction (blockage of the common bile duct or gallbladder duct).
Frequent episodes of hepatic colic.
Radiopaque calcified gallbladder stones.
Violation of gallbladder contractility.
Unsuccessful outcome of portoenterostomy or lack of adequate biliary outflow in children with biliary atresia.
Interaction with other medicinal products and other types of interactions
When using the drug simultaneously with other medications, it is possible:
with antacids containing aluminum; cholestyramine, colestipol - reduced absorption of ursodeoxycholic acid in the intestine. Do not use these drugs simultaneously. If the use of drugs containing one of these substances is necessary, they should be used at least 2 hours before or after taking UrsocholÒ capsules;
with cyclosporine - increased absorption of the latter in the intestine. Periodic monitoring of cyclosporine levels in the blood is necessary and, if necessary, its dose should be adjusted;
with ciprofloxacin – decreased absorption of the latter in the intestine;
with hypolipidemic drugs (clofibrate, bezafibrate, probucol), estrogens - weakening of the effect of ursodeoxycholic acid due to increased cholesterol levels in bile.
Ursodeoxycholic acid reduces the maximum plasma concentration (Cmax) and the area under the curve (AUC) for the calcium antagonist nitrendipine. Based on this, as well as on the single report of interaction with the substance dapsone (reduction of the therapeutic effect) and on in vitro studies, it can be assumed that the drug induces the activity of the cytochrome P450 3A4 enzyme, which is involved in drug metabolism.
Therefore, in the case of simultaneous use of drugs that are metabolized with the participation of this enzyme, caution should be exercised and it should be taken into account that dose adjustment may be required.
Estrogen hormones, as well as drugs to reduce blood cholesterol levels, can increase the secretion of cholesterol by the liver and thus contribute to the formation of gallstones, which is the opposite effect of ursodeoxycholic acid, which is used to dissolve them.
In a clinical study in healthy volunteers, concomitant administration of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) resulted in a slight increase in rosuvastatin plasma concentrations. The clinical significance of this interaction, as well as its significance for other statins, is unknown.
Application features
Taking the drug Ursochol should be done under the supervision of a doctor.
Liver function tests (AST, ALT and GGT) should be monitored every 4 weeks during the first 3 months of treatment and every 3 months thereafter. This allows for the assessment of response or non-response in PBC patients and the early detection of potential liver dysfunction, particularly in patients with advanced PBC.
Uses for dissolving cholesterol gallstones
In order to assess the progress of treatment, as well as for timely detection of any signs of calcification of stones, depending on the size of the stones, visualization of the gallbladder (oral cholecystography) with examination of the obscurations in the patient's standing and supine positions (under ultrasound guidance) should be performed 6-10 months after the start of treatment.
Ursochol should not be used if the gallbladder cannot be visualized on X-rays or in the case of calcification of stones, impaired gallbladder contractility, or frequent hepatic colic.
Women taking Ursochol to dissolve gallstones should use an effective non-hormonal method of contraception, as hormonal contraceptives may increase the formation of gallstones.
Treatment of patients with advanced stage PBC
Decompensated liver cirrhosis has been reported extremely rarely, which may partially regress after discontinuation of therapy.
In patients with PBC, very rarely, symptoms may worsen at the beginning of treatment, for example, itching may increase. In such cases, the dose of Ursochol should be reduced to 1 capsule per day; then the dose should be gradually increased as described in the section "Method of administration and dosage".
If diarrhea occurs, the dosage should be reduced; if diarrhea persists, treatment should be discontinued.
Use during pregnancy or breastfeeding
Animal studies have not shown any effect of ursodeoxycholic acid on fertility. There are no data on the effect on fertility in humans.
There are insufficient data on the use of ursodeoxycholic acid in pregnant women. Animal studies have shown reproductive toxicity in early pregnancy. Ursochol should not be used during pregnancy unless clearly necessary. Women of childbearing potential should only take the drug if they are using reliable contraception.
It is recommended to use non-hormonal contraceptives or oral contraceptives with a low estrogen content. Patients receiving Ursochol for the dissolution of gallstones should use effective non-hormonal contraceptives, since hormonal oral contraceptives may increase the formation of gallstones. Pregnancy should be excluded before starting treatment.
According to several recorded cases of use of the drug in breastfeeding women, the content of ursodeoxycholic acid in breast milk was extremely low, therefore, no adverse effects should be expected in children receiving such milk.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug does not affect the reaction speed when driving or working with other mechanisms.
Method of administration and doses
There are no age restrictions for the use of Ursochol. The drug should be administered orally to patients weighing more than 47 kg. For patients weighing less than 47 kg or who have difficulty swallowing capsules, the drug should be administered in the form of a suspension.
To dissolve cholesterol gallstones.
The drug should be administered once a day in the evening before bedtime at a dose of approximately 10 mg/kg of body weight.
| Body weight (kg) | |
| 47-60 kg | 2 | |
| 61-80 kg | 3 | |
| 81-100 kg | 4 | |
| over 100 kg | 5 | |
Swallow the capsules whole with a small amount of liquid. Take them regularly.
The duration of treatment is usually 6-24 months. If a reduction in the size of the gallstones is not observed after 12 months, drug therapy should be discontinued.
The effectiveness of the treatment should be checked by ultrasound or X-ray every 6 months. Additional studies should be performed to detect possible calcification of the stones. If this occurs, treatment should be discontinued.
For the treatment of gastritis with bile reflux.
The drug should be used once a day in the evening before bedtime in a dose of 1 capsule. Swallow the capsules whole, with a small amount of liquid.
The duration of treatment depends on the patient's condition and is usually 10-14 days. The doctor must decide on the duration of treatment in each case individually.
For the symptomatic treatment of primary biliary cirrhosis (PBC).
The daily dose of the drug depends on body weight and is approximately 14 ± 2 mg/kg body weight. In the first 3 months of treatment, divide the daily dose into 3 doses, then, when liver function indicators improve, use the drug once a day in the evening.
| Body weight (kg) | Daily dose (mg/kg body weight) | Capsules | | | |
| first 3 months | in the future | | | | |
| morning | day | evening | evening (1 time per day) | | |
| 47-62 | 12-16 | 1 | 1 | 1 | 3 |
| 63-78 | 13-16 | 1 | 1 | 2 | 4 |
| 79-93 | 13-16 | 1 | 2 | 2 | 5 |
| 94-109 | 14-16 | 2 | 2 | 2 | 6 |
| over 110 | | 2 | 2 | 3 | 7 |
Swallow the capsules whole with a small amount of liquid. Take them regularly.
The duration of treatment with the drug for primary biliary cirrhosis may be unlimited in time.
In patients with primary biliary cirrhosis, at the beginning of treatment, a worsening of clinical symptoms, for example, increased itching, is possible. If this occurs, therapy should be continued at a dose of 1 capsule per day, then the dose should be gradually increased (increasing the daily dose by 1 capsule every week) until the prescribed dosage regimen is reached.
Use in children
For children with cystic fibrosis aged 6 to 18 years, the dosage is 20 mg/kg/day and is divided into 2-3 doses, with a subsequent increase in the dose to 30 mg/kg/day if necessary.
Body weight (kg) | Daily dose (mg/kg) | Ursohol, 250 mg capsules | | |
| Morning | Day | Evening | | |
| 20-29 | 17-25 | 1 | - | 1 |
| 30-39 | 19-25 | 1 | 1 | 1 |
| 40-49 | 20-25 | 1 | 1 | 2 |
| 50-59 | 21-25 | 1 | 2 | 2 |
| 60-69 | 22-25 | 2 | 2 | 2 |
| 70-79 | 22-25 | 2 | 2 | 3 |
| 80-89 | 22-25 | 2 | 3 | 3 |
| 90-99 | 23-25 | 3 | 3 | 3 |
| 100-109 | 23-25 | 3 | 3 | 4 |
| >110 | | 3 | 4 | 4 |
Children.
For the dissolution of cholesterol gallstones, treatment of gastritis with bile reflux, and symptomatic treatment of PBC
There are no fundamental age restrictions for the use of Ursochol in children, but if the child weighs less than 47 kg and/or if the child has difficulty swallowing, it is recommended to use the drug in suspension form.
For the treatment of hepatobiliary disorders in cystic fibrosis
Apply to children aged 6 to 18 years.
Overdose
In cases of overdose, diarrhea is possible. Other symptoms of overdose are unlikely, since the absorption of ursodeoxycholic acid decreases with increasing dose and therefore its main amount is excreted with feces.
If diarrhea occurs, the dose should be reduced, and if diarrhea is persistent, therapy should be discontinued.
There is no need for specific measures. The consequences of diarrhea should be treated symptomatically, with restoration of fluid and electrolyte balance.
Additional information regarding special patient groups.
Long-term therapy with high doses of ursodeoxycholic acid (28-30 mg/kg/day) in patients with primary sclerosing cholangitis (off-label use) was associated with a higher incidence of serious adverse events.
Adverse reactions
The assessment of the frequency of adverse reactions is based on the following data:
Very common: >1/10.
Common: >1/100 and <1/10.
Uncommon: >1/1000 and <1/100.
Rare: >1/10,000 and <1/1,000.
Very rare: <1/10,000, including isolated cases.
Gastrointestinal: In clinical trials, pasty stools or diarrhea were commonly reported during treatment with ursodeoxycholic acid.
On the part of the liver and biliary tract: very rarely, calcification of gallstones is possible during treatment with ursodeoxycholic acid.
During the treatment of advanced stages of primary biliary cirrhosis, decompensation of liver cirrhosis was very rarely observed, which partially regressed after discontinuation of treatment.
On the part of the immune system: very rarely, allergic reactions are possible, including rash, urticaria.
Skin and subcutaneous tissue disorders: Very rarely, allergic reactions are possible, including rash and urticaria.
Expiration date
3 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25 °C.
Packaging
10 capsules in a contour blister pack; 5 or 10 contour blister packs in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
