Ukrliv oral suspension 250 mg/5 ml bottle 200 ml

Instructions for use Ukrliv oral suspension 250 mg/5 ml bottle 200 ml

Composition

active ingredient: ursodeoxycholic acid;

5 ml of suspension contain 250 mg of ursodeoxycholic acid;

excipients: microcrystalline cellulose-sodium carboxymethylcellulose, benzoic acid (E 210), xylitol, glycerin, sodium saccharin, sodium chloride, citric acid, monohydrate; sodium citrate, lemon flavor, purified water.

Dosage form

Oral suspension.

Main physicochemical properties: viscous white suspension with a lemon odor.

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 is normally found in human bile.

After oral administration, it reduces the cholesterol saturation of bile by slowing cholesterol absorption in the small intestine and reducing cholesterol secretion into bile. Apparently, as a result of cholesterol dispersion and the formation of liquid crystals, there is a gradual dissolution of gallstones.

According to modern ideas, the effect of ursodeoxycholic acid in liver diseases and cholestatic diseases is due to the relative replacement of lipophilic, detergent-like toxic bile acids with hydrophilic cytoprotective non-toxic ursodeoxycholic acid, as well as improving the secretory capacity of hepatocytes and immunoregulatory processes.

Application to children.

Cystic fibrosis.

There is evidence of long-term use of ursodeoxycholic acid (up to 10 years) in the treatment of children with hepatobiliary disorders associated with cystic fibrosis. In particular, 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 better effectiveness, treatment with ursodeoxycholic acid should be started immediately after the diagnosis of cystic fibrosis is clarified.

Pharmacokinetics

When taken orally, ursodeoxycholic acid 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 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 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 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

Symptomatic treatment of primary biliary cirrhosis (PBC) in the absence of decompensated liver cirrhosis.

For the dissolution of radiopaque cholesterol gallstones up to 15 mm in diameter in patients with a functioning gallbladder, regardless of the presence of gallstone(s).

For the treatment of hepatobiliary disorders in cystic fibrosis in children aged 1 month to 18 years.

Contraindication

Hypersensitivity to bile acids or to any of the excipients included in the preparation. Acute cholecystitis or acute cholangitis. Obstruction of the biliary tract (blockage of the common bile duct or the duct of the gallbladder). Frequent attacks of biliary (hepatic) colic. The presence of radiopaque calcified gallstones. Impaired gallbladder contractility. Unsuccessful outcome of portoenterostomy or lack of adequate bile outflow in children with biliary atresia.

Interaction with other medicinal products and other types of interactions

Ukrliv®, oral suspension, 250 mg/5 ml should not be used simultaneously with cholestyramine, colestipol or antacids containing aluminum hydroxide 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 a drug containing one of these substances is necessary, it should be taken at least 2 hours before or 2 hours after taking Ukrliv®, oral suspension, 250 mg/5 ml.

In some cases, Ukrliv®, oral suspension, 250 mg/5 ml may reduce the absorption of ciprofloxacin.

There is clinical evidence that concomitant administration of ursodeoxycholic acid (500 mg/day) and rosuvastatin (20 mg/day) to healthy volunteers resulted in a slight increase in rosuvastatin plasma concentrations. The clinical significance of this interaction, as well as its significance for other statins, has not been established.

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 the concomitant use of nifedipine and ursodeoxycholic acid is recommended. An increase in the dose of nifedipine may be necessary. In addition, a decrease in 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, no such effect was observed when ursodeoxycholic acid was studied in the interaction with budesonide, a proven substrate of cytochrome P450 3A.

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, used to dissolve them.

Application features

Ukrliv® suspension should be taken under the supervision of a physician.

During the first three months of treatment, liver function parameters AST (SGOT), ALT (SGPT) and g-GT should be checked every 4 weeks, and then every 3 months. This also allows to determine the presence or absence of response to treatment in patients with PBC, as well as to timely identify potential liver dysfunction, especially in patients with PBC in the late stages.

Use for dissolving cholesterol gallstones.

To assess the effectiveness of treatment and detect any calcification of gallstones in advance, depending on the size of the stone, it is necessary to conduct an examination of the general appearance of the gallbladder (oral cholecystography) and possible obstruction in the patient's standing and supine positions (ultrasound control) 6-10 months after the start of treatment.

It is not recommended to use Ukrliv®, oral suspension, 250 mg/5 ml, if the gallbladder is not visualized on X-rays or in case of calcification of stones, impaired gallbladder contractility, or frequent hepatic colic.

Women taking Ukrliv®, oral suspension, 250 mg/5 ml for the dissolution of 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, it is extremely rare for symptoms to worsen at the beginning of treatment, for example, itching may increase. In such cases, the dose of Ukrliva, oral suspension, 250 mg/5 ml should be reduced to 5 ml per day; then the dose should be gradually increased as described in the section “Method of administration and dosage”.

In case of diarrhea, it is recommended to reduce the dose of the drug, and in case of persistent diarrhea, treatment should be discontinued.

One measuring spoon (equivalent to 5 ml) of Ukrliva, oral suspension, 250 mg/5 ml contains 0.43 mmol (9.87 mg) sodium. This should be taken into account by patients on a controlled sodium diet.

Ability to influence reaction speed when driving vehicles or other mechanisms

No effect on the ability to drive and use machines was observed.

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. Ukrliv®, oral suspension, 250 mg/5 ml 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 Ukrliv®, oral suspension, 250 mg/5 ml 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, so no adverse effects should be expected in children receiving such milk.

Method of administration and doses

The following daily doses are recommended for various indications.

Approximately 10 mg ursodeoxycholic acid/kg body weight per day (see Table 1)

Table 1

* 1 measuring spoon (= 5 ml of suspension) contains 250 mg of ursodeoxycholic acid.

Ukrliv® suspension should be taken in the evening, before bedtime. The suspension 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 the stones have calcified 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 is approximately 14±2 mg ursodeoxycholic acid/kg body weight.

In the first 3 months of treatment, Ukrliv® suspension should be taken throughout 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

* 1 measuring spoon (= 5 ml of suspension) contains 250 mg of ursodeoxycholic acid.

A plastic disposable syringe without a needle can be used to measure doses.

Ukrliv® suspension should be taken according to the dosage regimen given in Table 2. It is necessary to adhere to the regularity of administration.

The use of Ukrliv® suspension 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 such cases, therapy should be continued by initially taking a reduced daily dose of Ukrliv® suspension, and then gradually increasing the dose (increasing the daily dose weekly) until the indicated dosage regimen is reached.

For the treatment of hepatobiliary disorders in cystic fibrosis.

For children with cystic fibrosis aged 1 month 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.

Children weighing less than 10 kg are very rarely affected. In such cases, it is recommended to use disposable syringes for the administration of the suspension for internal use.

Single doses for children weighing up to 10 kg should be drawn up with a syringe from the measuring spoon provided in the kit to a volume of 1.25 ml. For this purpose, a 2 ml disposable syringe with a graduation of 0.1 ml is used. Please note that disposable syringes are not included in the package.

To administer the required dose using a syringe

Before opening the bottle, the suspension must be shaken. Then, a small amount of the suspension must be poured into a measuring spoon. Draw a little more suspension than required into the syringe. Press the syringe plunger with your finger to remove air bubbles from the drawn suspension. Check the volume of the suspension in the syringe and adjust if necessary. Carefully introduce the contents of the syringe directly into the child's mouth.

Do not draw the syringe directly from the vial. Do not pour unused suspension from the measuring spoon or syringe back into the vial.

Table 3. Dosage regimen for children weighing less than 10 kg: 20 mg ursodeoxycholic acid/kg/day (volume measuring device - disposable syringe)

Table 4. Dosage regimen for children weighing more than 10 kg: 20-25 mg ursodeoxycholic acid/kg/day (volume measuring device - measuring spoon)

Table 5 * Conversion table

Children

For the dissolution of cholesterol gallstones and symptomatic treatment of PBC

There are no age restrictions for the use of this medicine. Dosage according to the section "Method of administration and doses".

For the treatment of hepatobiliary disorders in cystic fibrosis

Use in children from 1 month of age.

Overdose

Overdose may cause diarrhea. Overdose is unlikely, as the absorption of ursodeoxycholic acid decreases with increasing dose and most of it is excreted in the feces.

In case of diarrhea, the dose should be reduced; if diarrhea persists, therapy should be discontinued.

No specific countermeasures are necessary; the effects of diarrhea should be treated symptomatically, maintaining 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

Gastrointestinal: loose stools or diarrhea, severe pain in the right upper abdomen.

Liver and gallbladder: calcification of gallstones, decompensation of liver cirrhosis, which partially regressed after discontinuation of treatment.

Immune system disorders: hypersensitivity reactions, including rash (urticaria).

Expiration date

2 years.

Storage conditions

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

After first opening the bottle or jar, store the drug for no more than 4 months.

Packaging

200 ml of suspension in a bottle, in a cardboard box together with a measuring spoon.

Vacation category

According to the recipe.

Producer

"KUSUM FARM" LLC.

Location of the manufacturer and its business address

40020, Ukraine, Sumy region, Sumy city, Skryabina st., 54.