Instructions for use Ukrliv tablets 500 mg blister No. 100
Composition
active ingredient: ursodeoxycholic acid;
1 tablet contains ursodeoxycholic acid 500 mg;
excipients: microcrystalline cellulose, sodium starch glycolate (type A), povidone K-30, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: round biconvex tablets of white color, smooth on both sides.
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. ATC code A05B.
Pharmacological properties
Pharmacodynamics.
A small amount of ursodeoxycholic acid (UDCA) is normally found in human bile.
After oral administration, it reduces the cholesterol saturation of bile by inhibiting its absorption in the small intestine and reducing cholesterol secretion into bile. As a result of cholesterol dispersion and the formation of liquid crystals, gallstones gradually dissolve.
The effect of UDCA in liver diseases and cholestatic diseases is believed to be due to the relative replacement of lipophilic, detergent-like toxic bile acids with hydrophilic cytoprotective non-toxic UDCA, as well as to the improvement of the secretory capacity of hepatocytes and immunoregulatory processes.
Application to children.
Cystic fibrosis.
There is evidence of long-term use of UDCA (up to 10 years) in the treatment of children with hepatobiliary disorders associated with cystic fibrosis. In particular, the use of UDCA 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 UDCA should be started immediately after the diagnosis of cystic fibrosis is clarified.
Pharmacokinetics.
When administered orally, UDCA is rapidly absorbed in the small intestine and upper ileum by passive transport and in the terminal ileum by active transport. The extent of absorption is usually 60-80%. After absorption, the bile acid undergoes almost complete conjugation in the liver with the amino acids glycine and taurine, after which it is 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 UDCA 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 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 UDCA 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.
Biliary obstruction (blockage of the common bile duct or cystic duct).
Frequent attacks of biliary (hepatic) colic.
The presence of radiopaque calcified gallstones.
The contractility of the gallbladder is impaired.
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
The drug Ukrliv® should not be used simultaneously with cholestyramine, colestipol or antacids containing aluminum hydroxide and/or smectite, since these drugs bind UDCA in the intestine and, thus, prevent its absorption and reduce its effectiveness. If the use of a drug containing one of these substances is necessary, it should be taken at least 2 hours before or 2 hours after taking the drug Ukrliv®.
UDCA may increase the absorption of cyclosporine from the intestine. In this regard, patients taking cyclosporine should check the concentration of this substance in the blood and adjust the dose if necessary.
In some cases, UDCA may reduce the absorption of ciprofloxacin.
UDCA 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 nitrendipine and UDCA is recommended. An increase in the dose of nitrendipine 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 UDCA has the potential to induce cytochrome P450 3A enzymes. However, a well-designed interaction study of UDCA with budesonide, a proven substrate of cytochrome P450 3A, did not show this effect.
Estrogen hormones, as well as drugs to reduce blood cholesterol concentrations, such as clofibrate, can increase cholesterol secretion by the liver and thus contribute to the formation of gallstones, which is the opposite effect of UDCA, used to dissolve them.
Application features
The drug Ukrliv® should be taken under the supervision of a physician.
During the first three months of treatment, the following liver function parameters should be monitored: AST (SGOT), ALT (SGPT) and g-GT 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.
Use 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 gallstones, depending on the size of the stones, visualization of the gallbladder (oral cholecystography) should be performed with an examination of the obscurations in the patient's standing and supine positions (under ultrasound guidance) through
6-10 months after the start of treatment.
Ukrliv® should not be used if the gallbladder is not visualized on X-rays or in case of calcification of stones, impaired gallbladder contractility, or frequent hepatic colic.
Patients taking Ukrliv® 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 late-stage PBC.
Extremely rare cases of decompensated liver cirrhosis have been reported, 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 Ukrliv® should be reduced to one Ukrliv 250 mg tablet per day; then the dose should be gradually increased as described in the section "Method of administration and dosage".
If diarrhea occurs, it is recommended to reduce the dose of the drug, and in case of persistent diarrhea, treatment should be discontinued.
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy
Animal studies have not shown any effect of UDCA on fertility. There are no data on the effect on fertility in humans.
There are insufficient data on the use of UDCA in pregnant women. Animal studies have shown reproductive toxicity in early pregnancy. Ukrliv® should not be used during pregnancy unless clearly necessary. Women of childbearing potential should only take the drug if they use reliable contraception.
Women of reproductive age
It is recommended to use non-hormonal contraceptives or oral contraceptives with a low estrogen content. Patients receiving Ukrliv® 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.
Breast-feeding.
According to several recorded cases of use of the drug in breastfeeding women, the content of UDCA 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 machines was observed.
Method of administration and doses
For patients whose body weight is less than 47 kg or who have difficulty swallowing Ukrliv® tablets, another dosage form is available - Ukrliv®, oral suspension.
To dissolve cholesterol gallstones.
Approximately 10 mg UDCA per kilogram of body weight per day (see Table 1).
Table 1
Body weight (kg) | Number of tablets |
| up to 60 | 1 |
| 61-80 | 1 ½ * |
| 81-100 | 2 |
| more than 100 | 2 ½ * |
*Instead of ½ tablet of the drug Ukrliv® 500 mg, you can use 1 tablet of the drug Ukrliv®, 250 mg.
The tablets must 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 occurs, treatment should be discontinued.
For the symptomatic treatment of primary biliary cirrhosis (PBC).
The daily dose depends on body weight and varies from 1 ½ to 3 ½ * tablets (14±2 mg UDCA per kilogram of body weight).
In the first 3 months of treatment, the drug Ukrliv® should be taken during the day, dividing the daily dose into several doses. If liver function indicators improve, the daily dose can be taken once a day, in the evening.
Table 2
| Body weight (kg) | Daily dose (mg/kg b.w.) | Ukrliv®, 500 mg tablets |
| first 3 months | in the future |
| morning | day | evening | evening (1 time per day) |
| 47-62 | 12–16 | ½ * | ½ * | ½ * | 1 ½ * |
| 63-78 | 13–16 | ½ * | ½ * | 1 | 2 |
| 79-93 | 13–16 | ½ * | 1 | 1 | 2 ½ * |
| 94-109 | 14–16 | 1 | 1 | 1 | 3 |
| more than 110 | 1 | 1 | 1 ½ * | 3 ½ * | |
*Instead of ½ tablet of the drug Ukrliv®, 500 mg, you can use 1 tablet of the drug Ukrliv®, 250 mg.
The tablets should be swallowed without chewing, with liquid. The drug should be used regularly.
The use of the drug Ukrliv® in PBC can be unlimited in time.
In patients with PBC, clinical symptoms such as pruritus may rarely worsen at the beginning of treatment. If this occurs, therapy should be continued at 1 tablet of Ukrliva 250 mg per day, then the dose should be gradually increased (increase the daily dose by 250 mg each week) until the indicated dosage regimen is reached.
Application to 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) | Ukrliv®, 500 mg tablets |
| Morning | Day | Evening |
| 20–29 | 17-25 | ½ * | - | ½ * |
| 30–39 | 19-25 | ½ * | ½ * | ½ * |
| 40–49 | 20-25 | ½ * | ½ * | 1 |
| 50–59 | 21-25 | ½ * | 1 | 1 |
| 60–69 | 22-25 | 1 | 1 | 1 |
| 70–79 | 22-25 | 1 | 1 | 1 ½ * |
| 80–89 | 22-25 | 1 | 1 ½ * | 1 ½ * |
| 90–99 | 23-25 | 1 ½ * | 1 ½ * | 1 ½ * |
| 100–109 | 23-25 | 1 ½ * | 1 ½ * | 2 |
| >110 | 1 ½ * | 2 | 2 | |
*Instead of ½ tablet of the drug Ukrliv®, 500 mg, you can use 1 tablet of the drug Ukrliv®, 250 mg.
Children
For the dissolution of cholesterol gallstones and symptomatic treatment of PBC
There are no fundamental age restrictions for the use of the drug Ukrliv® in children, but children weighing less than 47 kg and/or children who have difficulty swallowing are recommended to use the drug 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 case of overdose, diarrhea is possible. Other symptoms of overdose are unlikely, since the absorption of UDCA decreases with increasing dose and therefore the majority of the dose taken 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. Treatment of the consequences of diarrhea is symptomatic and involves restoring fluid and electrolyte balance.
Additional information regarding special patient groups.
Long-term therapy with high doses of UDCA (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
Adverse reactions are listed below by system organ class and frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000, including isolated cases), unknown (frequency cannot be estimated from the available data).
On the part of the gastrointestinal tract: often - pasty stools, diarrhea; very rarely - severe pain in the right upper abdomen.
On the part of the liver and gallbladder: very rarely - calcification of gallstones, decompensation of liver cirrhosis, which partially regressed after discontinuation of treatment.
On the part of the immune system: very rarely - hypersensitivity reactions, including rash (urticaria).
Reporting suspected adverse reactions after registration of a medicinal product is an important procedure. This allows for continued monitoring of the benefit/risk balance when using this medicinal product. Healthcare professionals should report all suspected adverse reactions to the State Expert Center of the Ministry of Health of Ukraine and to the applicant via the feedback form on the website: https://kusum.ua/pharmacovigilance/.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 or 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
"KUSUM FARM" LLC.
Location of the manufacturer and address of its place of business
40020, Ukraine, Sumy region, Sumy city, Skryabina st., 54.
