Instructions Ursoliv capsules 250 mg blister No. 50
Composition
active ingredient: ursodeoxycholic acid;
1 capsule contains ursodeoxycholic acid 250 mg;
Excipients: corn starch, pregelatinized starch, magnesium stearate, colloidal anhydrous silicon dioxide.
Dosage form
Capsules.
Main physicochemical properties: opaque oblong white or almost white hard gelatin capsules of size “0” containing white or almost white granular powder.
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.
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 a number of 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 ultimately 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 treatment of biliary reflux gastritis.
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.
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
The drug should not be used simultaneously with cholestyramine, colestipol or antacids containing aluminum hydroxide and/or smectite, as these drugs bind ursodeoxycholic acid in the intestine and thus prevent its absorption and effectiveness. If the use of drugs containing one of the substances is necessary, they should be taken at least 2 hours before or 2 hours after taking Ursoliv capsules.
The drug may increase the absorption of cyclosporine from the intestine. In patients treated with cyclosporine, the doctor should check the concentration of this substance in the blood and, if necessary, adjust the dose of cyclosporine.
In some cases, the drug may reduce the absorption of ciprofloxacin.
In a clinical study in healthy volunteers, co-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 and area under the concentration-time curve of the calcium antagonist nitrendipine in healthy volunteers.
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 concentrations, 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 Ursoliv 250 mg capsules should be done under the supervision of a physician.
During the first 3 months of treatment, liver function tests (AST, ALT and GGT) should be monitored every 4 weeks, and then every 3 months. This allows for the determination of the presence or absence of response to treatment in patients with PBC, as well as for the timely 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 for the 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.
Ursoliv 250 mg capsules should not be used if the gallbladder cannot be visualized on X-rays or in case of calcification of stones, impaired gallbladder contractility or frequent hepatic colic.
Women taking Ursoliv 250 mg 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 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 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. 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 receiving Ursoliv 250 mg 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 breastfeeding women, the content of ursodeoxycholic acid in milk was very 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 speed of driving or using other mechanisms was observed.
Method of administration and doses
To dissolve cholesterol gallstones
Approximately 10 mg ursodeoxycholic acid/kg body weight (see Table 1)
Table 1
| Body weight (kg) | Number of capsules |
up to 60 61-80 81-100 over 100 | 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 the size of the gallstones 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 has occurred, treatment should be discontinued.
For the treatment of biliary reflux gastritis
Usually, for the treatment of gastritis with reflux, bile capsules are taken for 10-14 days. The duration of use depends on the patient's condition. The doctor must decide on the duration of treatment in each case individually.
For symptomatic treatment of 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, the daily dose should be divided 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) | Capsules |
| first 3 months | in the future |
| morning | day | evening | evening (once a 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 capsules should be swallowed whole with liquid. It is necessary to adhere to the regularity of administration.
The use of the drug 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 capsule per day, then the dose should be gradually increased (increase the daily dose by 1 capsule per 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.
Table 3
Body weight (kg) | Daily dose (mg/kg) | Ursoliv, capsules, 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 Ursoliv in children, but the capsules are not used in children weighing less than 47 kg and/or if the child has difficulty swallowing.
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, 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 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: > 1/10 00 and < 1/100.
Rare: > 1/10,000 and < 1/1,000.
Very rare: <1/10,000, including isolated cases.
Gastrointestinal tract
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
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 is 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.
The drug cannot be used after the expiration date indicated on the package.
Storage conditions
Store in the original packaging out of the reach of children at a temperature not exceeding 25 °C.
Packaging
10 capsules in a blister; 5 or 10 blisters in a cardboard box
Vacation category
According to the recipe.
Producer
Mega Lifesciences Public Company Limited.
Plant 2 515/1 Moo 4, Soi 8, Bangpoo Industrial Estate, Pattana 3 Road, Phraeksa, Mueang, 10280 Samutprakarn Thailand/Plant 2 515/1 Moo 4, Soi 8, Bangpoo Industrial Estate, Pattana 3 Road, Phraeksa, Mueang, 10280 Samutprakarn Thailand.
