Instructions Ursis tablets 250 mg No. 50
Composition
active ingredient: ursodeoxycholic acid;
1 tablet contains ursodeoxycholic acid 250 mg;
excipients: microcrystalline cellulose, crospovidone, povidone, polysorbate 80, talc, colloidal anhydrous silicon dioxide, magnesium stearate;
shell: Opadry Clear film coating mixture: hypromellose (hydroxypropylmethylcellulose), talc, polyethylene glycol (macrogol).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, coated with a white or almost white film coating.
Pharmacotherapeutic group
Drugs used to treat the liver and biliary tract. Drugs used in case of biliary pathology.
ATX code A05A A02.
Drugs used in cases of liver disease are 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 the 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
For the dissolution of radiopaque cholesterol gallstones up to 15 mm in diameter in patients with a functioning gallbladder, despite the presence of gallstone(s).
For the 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.
Liver cirrhosis in the decompensation stage.
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
Ursodeoxycholic acid may increase the absorption of cyclosporine from the intestine. In patients taking cyclosporine, the doctor should check the concentration of this substance in the blood and, if necessary, adjust the dose of cyclosporine.
In some cases, ursodeoxycholic acid may reduce the absorption of ciprofloxacin.
It is known that in a clinical study in healthy volunteers, the combined use of ursodeoxycholic acid (500 mg per day) and rosuvastatin (20 mg per day) resulted in a slight increase in the plasma concentration of rosuvastatin. The clinical significance of this interaction, as well as its significance for other statins, is unknown.
Ursodeoxycholic acid has been shown to reduce the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of the calcium antagonist nitrendipine in healthy volunteers. Careful monitoring of the effect of the 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 in vitro data, 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 levels, such as clofibrate, can increase the secretion of cholesterol by the liver and thus cause gallstone formation, which is the opposite effect of ursodeoxycholic acid, which is used to dissolve them.
Therefore, in the case of concomitant use of drugs that are metabolized by the P450 3A enzyme, special caution should be exercised and it should be borne in mind that dose adjustment is possible if necessary.
Application features
Taking the drug Ursis® should be carried out under the supervision of a physician.
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 determination of the response or non-response in patients with PBC 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 to detect any signs of calcification of stones in a timely manner, 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.
Ursis® 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 using Ursis® 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 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 Ursis® should be reduced to 1 tablet 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
Pregnancy. There are insufficient data from the use of ursodeoxycholic acid in pregnant women. Animal studies have shown reproductive toxicity in early pregnancy. The drug 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 using Ursis® 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.
Breastfeeding. According to several reported cases of use of the drug in breastfeeding women, the content of ursodeoxycholic acid in breast milk was very low, so no adverse effects should be expected in children receiving such milk.
Fertility: Animal studies have not shown any effect of ursodeoxycholic acid on fertility. There are no data on the effect on fertility in humans.
Ability to influence reaction speed when driving vehicles or other mechanisms
No effects on the ability to drive or use other mechanisms were observed.
Method of administration and doses
For patients weighing less than 47 kg or who have difficulty swallowing tablets, it is recommended to use ursodeoxycholic acid in another dosage form, such as a suspension.
To dissolve cholesterol gallstones
Approximately 10 mg ursodeoxycholic acid/kg body weight.
| Body weight | Number of tablets |
up to 60 kg 61‒80 kg 81‒100 kg over 100 kg | 2 3 4 5 |
The tablets should be swallowed whole with water, once a day in the evening before bedtime.
The tablets must 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 symptomatic treatment of primary biliary cirrhosis (PBC)
The daily dose depends on body weight and varies from 3 to 7 tablets (14 ± 2 mg ursodeoxycholic acid/kg body weight).
During the first 3 months of treatment, the drug should be taken throughout the day, dividing the daily dose into 3 doses. If liver function indicators improve, the daily dose can be taken once a day, in the evening.
| Body weight (kg) | Daily dose (mg/kg body weight) | Tablets |
| 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 | |
The tablets should be swallowed whole with liquid. It is necessary to adhere to the regularity of administration.
The use of the drug Ursis® in primary biliary cirrhosis may be unlimited in time.
In patients with primary biliary cirrhosis, a rare worsening of clinical symptoms, such as increased itching, may occur at the beginning of treatment. In this case, therapy should be continued at 1 tablet of 250 mg per day, then the dose should be gradually increased (increase the daily dose by 1 tablet every week) until the prescribed dosage regimen is reached.
Use in children
For children aged 6 to 18 years with cystic fibrosis, the dosage is 20 mg/kg/day, divided into 2–3 doses, with a subsequent increase in dose to 30 mg/kg/day if necessary.
Body weight (kg) | Daily dose (mg/kg) | tablets of 250 mg |
| 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 biliary reflux gastritis and symptomatic treatment of PBC: there are no fundamental age restrictions for the use of Ursis® 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 suspension.
For the treatment of hepatobiliary disorders in cystic fibrosis: use in children aged 6 to 18 years.
Overdose
In case of overdose, diarrhea is possible. Other symptoms of overdose are unlikely, since the absorption of ursodeoxycholic acid decreases with increasing dose, so 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. 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 reactions.
Side effects
Gastrointestinal: During treatment with ursodeoxycholic acid, pasty stools or diarrhea have been reported frequently.
During the treatment of primary biliary cirrhosis, severe abdominal pain localized in the right hypochondrium was noted.
During the treatment of advanced stages of primary biliary cirrhosis, decompensation of liver cirrhosis is observed, which partially regressed after discontinuation of treatment.
Hypersensitivity reactions: Allergic reactions, including rash, urticaria, are possible.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a pack.
10 tablets in a blister; 5 blisters in a pack.
10 tablets in a blister; 10 blisters in a pack.
Vacation category
According to the recipe.
Producer
JSC "KYIV VITAMIN FACTORY".
Location of the manufacturer and address of its place of business
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua
