Instructions Ursoker capsules 250 mg blister No. 100
Composition
active ingredient: ursodeoxycholic acid;
1 capsule contains ursodeoxycholic acid 250 mg;
excipients: corn starch, colloidal anhydrous silicon dioxide, magnesium stearate, titanium dioxide (E 171), gelatin.
Dosage form
The capsules are hard.
Main physicochemical properties:
250 mg capsules: hard gelatin capsules, size “0”, white body and cap.
Pharmacotherapeutic group
Drugs used for the treatment of the liver and biliary tract. Drugs used in biliary pathology. ATX code A05A A02.
Drugs used in liver diseases, lipotropic substances. ATX code A05B.
Pharmacological properties
Pharmacodynamics.
A small amount of ursodeoxycholic acid has been found in human bile.
After oral administration, it reduces the cholesterol saturation of bile by inhibiting its absorption in the intestine and reducing cholesterol secretion into the bile. Perhaps due to the dispersion of cholesterol and the formation of liquid crystals, the gradual dissolution of gallstones occurs.
According to current knowledge, 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, provided that 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.
When administered orally, ursodeoxycholic acid is rapidly absorbed in the jejunum and upper ileum by passive transport, and in the terminal ileum by active transport. The absorption rate is usually 60-80%. After absorption, the bile acid undergoes almost complete conjugation in the liver with the amino acids glycine and taurine and is then excreted in the bile. The first-pass clearance through the liver is up to 60%.
Depending on the daily dose and the underlying liver disorder or condition, the more hydrophilic ursodeoxycholic acid accumulates in the bile. At the same time, there is a relative decrease in other more lipophilic bile acids.
Under the influence of intestinal bacteria, partial degradation occurs to 7-ketolithocholic and lithocholic acids. Lithocholic acid is hepatotoxic and causes damage to the liver parenchyma 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 then in the feces.
The biological half-life of ursodeoxycholic acid is 3.5–5.8 days.
Indication
¾ For the 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.
¾ For the treatment of biliary reflux gastritis.
¾ For symptomatic treatment of primary biliary cirrhosis (PBC) in the absence of decompensated liver cirrhosis.
¾ For the treatment of hepatobiliary disorders in cystic fibrosis in children aged 6 to 18 years.
Contraindication
¾ Hypersensitivity to the active substance, bile acids or to any other excipients of the medicinal product.
¾ Acute inflammation of the gallbladder or bile ducts.
¾ Bile duct obstruction (blockage of the common bile duct or the gallbladder duct).
¾ Frequent episodes of hepatic colic.
¾ Radiopaque calcified gallstones.
¾ Violation of gallbladder contractility.
¾ Unsuccessful outcome of portoenterostomy or lack of adequate biliary outflow in children with biliary atresia.
Interaction with other drugs and other types of interactions.
Ursocare® capsules should not be used simultaneously with cholestyramine, colestipol or antacids containing aluminum hydroxide and/or smectite (aluminum oxide), as these drugs bind ursodeoxycholic acid in the intestine and thus prevent its absorption and reduce its effectiveness. If the use of drugs containing one of the listed substances is necessary, they should be taken at least 2 hours before or 2 hours after taking Ursocare®.
In some cases, ursodeoxycholic acid may reduce the absorption of ciprofloxacin.
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 plasma concentrations of rosuvastatin. The clinical significance of this interaction, as well as its relevance to other statins, is unknown.
Ursodeoxycholic acid has been shown to reduce the peak plasma concentration (Cmax) and area under the curve (AUC) of the calcium antagonist nitrendipine in healthy volunteers. Careful monitoring of the outcome of concomitant use of nifedipine and ursodeoxycholic acid is recommended. An increase in the dose of nifedipine may be required.
In addition, a weakening of the therapeutic effect of dapsone has been reported.
These data, as well as data from in vitro studies, suggest that ursodeoxycholic acid has the potential to induce cytochrome P450 3A enzymes. However, in a well-designed interaction study with budesonide, a proven substrate of cytochrome P450 3A, no such effect was observed.
Estrogen hormones, as well as drugs to reduce blood cholesterol concentrations, such as clofibrate, 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.
Application features
Taking the drug Ursocare® should be carried out under the supervision of a physician.
Liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT)] should be monitored every 4 weeks during the first 3 months of treatment and every 3 months thereafter. This allows for the determination of the response or non-response in patients with PBC and the early detection of potential liver dysfunction, especially in patients with advanced PBC.
Uses for dissolving cholesterol gallstones
In order to assess the progress of treatment, as well as to timely detect 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.
Ursocare® capsules should not be used if the gallbladder cannot be visualized on X-rays, as well as in the case of calcification of stones, impaired gallbladder contractility, or frequent hepatic colic.
Women taking Ursocare® capsules 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 primary biliary cirrhosis (PBC)
Decompensated liver cirrhosis has been reported very 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 Ursocare® capsules should be reduced to one 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. Ursocare® capsules 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 Ursocare® capsules for the dissolution of gallstones should use effective non-hormonal contraceptives, since hormonal oral contraceptives may increase the risk of gallstone formation. Pregnancy should be excluded before starting treatment.
According to several recorded cases of use of the drug in nursing mothers, the content of ursodeoxycholic acid in breast milk was extremely low, so no adverse effects should be expected in children receiving such milk.
Ability to influence reaction speed when driving vehicles or other mechanisms
No effect on the ability to drive or use other mechanisms was observed.
Method of administration and doses
For patients whose body weight is less than 47 kg or who have difficulty swallowing Ursocare® capsules, it is recommended to use ursodeoxycholic acid in the form of a suspension.
Approximately 10 mg ursodeoxycholic acid/kg body weight (see Table 1).
Table 1
| Body weight | Number of capsules |
up to 60 kg 61‒80 kg 81‒100 kg over 100 kg | 2 3 4 5 |
The capsules should be swallowed whole with water, once a day in the evening before bedtime.
Capsules should be taken regularly.
The time required for gallstones to dissolve is usually 6–24 months. If a reduction in gallstone size is not observed after 12 months of treatment, therapy should not be continued.
The success of the treatment should be checked every 6 months by ultrasound or X-ray. Additional tests should be performed to check whether calcification of the stones has occurred over time. If this occurs, treatment should be discontinued.
For the treatment of biliary reflux gastritis
1 capsule of Ursocare® once a day with some liquid in the evening before bedtime.
Usually, for the treatment of gastritis with reflux, Ursocare® bile capsules are taken for 10-14 days. The duration of use depends on the patient's condition. The doctor should decide on the duration of treatment in each case individually.
For the symptomatic treatment of primary biliary cirrhosis (PBC)
The daily dose depends on body weight and varies from 3 to 7 capsules (14 ± 2 mg ursodeoxycholic acid/kg body weight).
During the first 3 months of treatment, Ursoker® should be taken throughout the day, dividing the daily dose into 3 doses. If liver function improves, the daily dose can be taken once a day in the evening.
Table 2
| Body weight (kg) | Daily dose (mg/kg body weight) | Ursoker®, 250 mg capsules | | | |
| first 3 months | in the future | | | | |
| morning | day | evening | evening (1 time per day) | | |
| 47‒62 | 12-16 | 250 mg | 250 mg | 250 mg | 750 mg |
| 63‒78 | 13-16 | 250 mg | 250 mg | 500 mg | 1000 mg |
| 79‒93 | 13-16 | 250 mg | 500 mg | 500 mg | 1250 mg |
| 94‒109 | 14‒16 | 500 mg | 500 mg | 500 mg | 1500 mg |
| over 110 | 500 mg | 500 mg | 750 mg | 1750 mg | |
The capsules should be swallowed whole with liquid. It is necessary to adhere to the regularity of administration.
The use of ursodeoxycholic acid in primary biliary cirrhosis may be unlimited in time.
In patients with primary biliary cirrhosis, a worsening of clinical symptoms, such as increased itching, may occur rarely at the beginning of treatment. In this case, therapy should be continued by taking 1 capsule of Ursocare® per day, then gradually increasing the dose (increasing the daily dose by 1 capsule each week) until the prescribed dosage regimen is reached.
Use in children
For children with cystic fibrosis aged 6 to 18 years, the dose is 20 mg/kg/day divided into 2–3 doses, with a subsequent increase to 30 mg/kg/day if necessary.
| Body weight (kg) | Daily dose (mg/kg) | Ursoker®, 250 mg capsules | | |
| morning | day | evening | | |
| 20–29 | 17–25 | 250 mg | --- | 250 mg |
| 30–39 | 19–25 | 250 mg | 250 mg | 250 mg |
| 40–49 | 20–25 | 250 mg | 250 mg | 500 mg |
| 50–59 | 21–25 | 250 mg | 500 mg | 500 mg |
| 60–69 | 22–25 | 500 mg | 500 mg | 500 mg |
| 70–79 | 22–25 | 500 mg | 500 mg | 750 mg |
| 80–89 | 22–25 | 500 mg | 750 mg | 750 mg |
| 90–99 | 23–25 | 750 mg | 750 mg | 750 mg |
| 100–109 | 23–25 | 750 mg | 750 mg | 1000 mg |
| >110 | 750 mg | 1000 mg | 1000 mg | |
Children.
For the dissolution of cholesterol gallstones, treatment of biliary reflux gastritis, and symptomatic treatment of PBC.
There are no fundamental age restrictions for the use of ursodeoxycholic acid in children, but if the child weighs less than 47 kg and/or if the child has difficulty swallowing, it is recommended to use ursodeoxycholic acid in the form of a suspension.
For the treatment of hepatobiliary disorders in cystic fibrosis.
Apply to children aged 6 to 18 years.
Overdose
In cases of overdose, diarrhea may occur. Other symptoms of overdose are unlikely, since the absorption of ursodeoxycholic acid decreases with increasing dose and therefore most of it is excreted in the 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, and the effects 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
Within each group, adverse events are presented in order of decreasing severity.
Gastrointestinal disorders
In clinical trials, pasty stools or diarrhea were commonly reported during treatment with ursodeoxycholic acid.
Very rarely, severe abdominal pain localized in the right hypochondrium was noted during the treatment of primary biliary cirrhosis.
Liver and gallbladder disorders
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.
Hypersensitivity reactions
Very rarely, allergic reactions are possible, including rash and urticaria.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
20 capsules in a blister; 1 blister in a cardboard box; 25 capsules in a blister; 2 or 4 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
A. B. C. PHARMACY S. P. A.
ABC PHARMACEUTICALS SPA
Location of the manufacturer and address of its place of business
Via Cantone Moretti, 29 (locality Localita San Bernardo) - 10015 Ivrea (TO), Italy.
Via Cantone Moretti, 29 (Loc. Localita' San Bernardo) - 10015 Ivrea (TO), Italy.
Applicant
EURODRAG LABORATORIES.
EURODRUG LABORATORIES.
Applicant's location
Kortrijkzesteenweg 214 bus 2, 9830 Sint-Martens-Latem, Belgium.
Kortrijksesteenweg 214 bus 2, 9830 Sint-Martens-Latem, Belgium.
