Ursoliv^® (Capsules) Instructions for Use

Marketing Authorization Holder

Avva Rus, JSC (Russia)

ATC Code

A05AA02 (Ursodeoxycholic acid)

Active Substance

Ursodeoxycholic acid (Rec.INN registered by WHO)

Dosage Form

Ursoliv®

Capsules 250 mg: 10, 20, 30, 50, or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin No. 00, with a white body and cap; the capsule contents are a granulated powder of white or almost white color.

Excipients: lactulose – 300 mg, talc – 18 mg, microcrystalline cellulose – to obtain capsule contents weighing 600 mg.

Hard gelatin capsules:
Body composition titanium dioxide – 2.1119%, gelatin – up to 100%.
Cap composition: titanium dioxide – 2.1119%, gelatin – up to 100%.

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.

Clinical-Pharmacological Group

Hepatoprotective agent with choleretic and cholelitholytic action

Pharmacotherapeutic Group

Means for the treatment of diseases of the liver and biliary tract; agents for the treatment of diseases of the biliary tract; bile acids and their derivatives

Pharmacological Action

It has hepatoprotective, choleretic, cholelitholytic, hypolipidemic, hypocholesterolemic, and some immunomodulatory effects.

In vitro studies have shown that Ursodeoxycholic acid (UDCA) has a direct protective effect on liver cells and reduces the hepatotoxicity of hydrophobic bile acid salts.

The main effects of UDCA on cholesterol metabolism include: reducing cholesterol secretion, decreasing its intestinal absorption, and stimulating the release of cholesterol from cholesterol stones into bile. UDCA, by inhibiting HMG-CoA reductase, also has a moderate suppressive effect on cholesterol synthesis in the liver and increases the solubility of cholesterol in the biliary system. It causes partial or complete dissolution of cholesterol gallstones when used enterally and reduces the saturation of bile with cholesterol. It stimulates the formation and secretion of bile and accelerates the excretion of toxic bile acids through the intestines.

When taken orally, the proportion of UDCA in the total bile acid pool increases significantly. UDCA competes with other bile acids during absorption in the small intestine and during penetration through the hepatocyte membrane, which reduces the absorption of toxic bile acids in the intestine and their entry into the liver, preventing their cytopathogenic effect. It reduces the lithogenicity of bile, increases the concentration of bile acids in it, causes an increase in gastric and pancreatic secretion, enhances lipase activity, and has a hypoglycemic effect.

It affects immunological reactions by reducing the pathological expression of HLA I histocompatibility complex antigens on hepatocytes and HLA II on cholangiocytes, suppresses the production of interleukin-2, and reduces the number of eosinophils.

Pharmacokinetics

Absorption

UDCA is absorbed in the small intestine (about 90%), with C_max in blood plasma after oral administration of a 250 mg dose being about 3.3 µg/ml, T_max – about 2 hours.

Distribution

The binding of unconjugated UDCA to plasma proteins in healthy people is at least 70%. It penetrates the placental barrier. With systematic administration at doses of 13-15 mg/kg/day, UDCA becomes the main bile acid in the serum and constitutes from 30 to 50% of the total bile acid content in the blood. The therapeutic effect of the drug depends on the concentration of UDCA in the bile.

Metabolism and Excretion

It is metabolized in the liver with conversion into taurine and glycine conjugates, which are secreted into the bile. About 50-70% of the orally administered dose is excreted in the bile. Excretion in urine does not exceed 1%. A small amount of UDCA not absorbed after oral administration enters the large intestine, where it is broken down by bacteria (7-dehydroxylation); the resulting lithocholic acid is partially absorbed from the large intestine, sulfated in the liver, and rapidly excreted as a sulfolithocholylglycine or sulfolithocholyltaurine conjugate.

Indications

• primary biliary cirrhosis without signs of decompensation (symptomatic therapy);
• Dissolution of small and medium-sized cholesterol stones in a functioning gallbladder;
• biliary reflux gastritis;
• chronic hepatitis of various origins;
• primary sclerosing cholangitis;
• cystic fibrosis (mucoviscidosis);
• non-alcoholic steatohepatitis;
• alcoholic liver disease;
• biliary dyskinesia.

ICD codes

Dosage Regimen

Orally. If swallowing is difficult, the capsule can be opened and its contents taken with a sufficient amount of liquid.

For dissolution of cholesterol gallstones, the capsules are taken in the evening, before bedtime, with a sufficient amount of liquid.

The dose is approximately 10 mg/kg of body weight daily, which corresponds to

2 capsules for patients weighing up to 60 kg;

3 capsules for patients weighing up to 80 kg;

4 capsules for patients weighing up to 100 kg;

5 capsules for patients weighing over 100 kg.

The duration of treatment is 6-12 months.

For prevention of recurrent stone formation, administration for several more months after stone dissolution is recommended.

For symptomatic treatment of primary biliary cirrhosis, the daily dose depends on body weight and ranges from 2 to 6 capsules (from 10 to 15 mg of ursodeoxycholic acid per 1 kg of body weight).

The drug is taken with food, with a sufficient amount of liquid.

The following administration regimen is recommended

For treatment of biliary reflux gastritis, 1 capsule once/day before bedtime is prescribed. The course of treatment is from 10-14 days to 6 months, if necessary – up to 2 years.

For chronic hepatitis of various origins (toxic, drug-induced, and others), non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, alcoholic liver disease, the average daily dose is 10-15 mg/kg in 2-3 divided doses. The duration of therapy is 6-12 months or more.

For primary sclerosing cholangitis, cystic fibrosis (mucoviscidosis), the average daily dose is 12-15 mg/kg; if necessary, the average daily dose can be increased to 20-30 mg/kg in 2-3 divided doses. The duration of therapy is from 6 months to several years.

For biliary dyskinesia of the hypokinetic type, the average daily dose is 10 mg/kg in 2 divided doses for a period from 2 weeks to 2 months. If necessary, the course of treatment is recommended to be repeated.

Adverse Reactions

From the digestive system nausea, vomiting, pain in the epigastric region and right hypochondrium, constipation, transient increase in liver transaminase activity; rarely – diarrhea (may be dose-dependent), calcification of gallstones. When treating primary biliary cirrhosis, transient decompensation of liver cirrhosis may be observed, which disappears after drug withdrawal.

Other headache, malaise, myalgia, dizziness, allergic reactions (skin itching, urticaria, angioedema), exacerbation of pre-existing psoriasis, alopecia.

Contraindications

• Size of cholesterol stones in the gallbladder more than 20 mm;
• Presence of radiopaque (high calcium content) stones of the gallbladder and common bile duct;
• Atrophy of the gallbladder in cholelithiasis, non-functioning gallbladder;
• Obstruction of the biliary tract;
• Acute inflammatory diseases of the gallbladder, bile ducts, and intestines;
• Liver cirrhosis in the stage of decompensation;
• Severe hepatic impairment;
• Severe renal impairment;
• Pancreatitis (active phase);
• Pregnancy;
• Lactation period;
• Adults and children weighing less than 34 kg (for this dosage form);
• Hypersensitivity to the components of the drug.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindication: severe hepatic impairment, liver cirrhosis in the stage of decompensation.

Use in Renal Impairment

Contraindication: severe renal impairment.

Pediatric Use

Contraindication: children weighing less than 34 kg.

Special Precautions

For the dissolution of gallstones, UDCA concretions must be cholesterol (non-radiopaque), no larger than 15-20 mm. In this case, the gallbladder must remain functional, and the patency of the cystic and common bile ducts must be preserved.

When prescribed for the dissolution of gallstones, it is necessary to perform a biochemical blood test monthly, and then every 3 months to determine the activity of liver transaminases, ALP, GGT, and the concentration of bilirubin. If elevated levels persist, UDCA should be discontinued.

To monitor the effectiveness of treatment, it is recommended to perform X-ray and ultrasound examinations of the biliary tract every 6 months.

If gallstones calcify, if the contractility of the gallbladder is impaired, or if there are frequent attacks of biliary colic, treatment should be discontinued. If partial dissolution of the concretions does not occur within 6-12 months after the start of therapy, it is unlikely that the treatment will be effective. Detection of a non-visualized gallbladder during treatment is evidence that complete dissolution of the concretions has not occurred, and treatment should be discontinued.

After complete dissolution of the stones, to exclude relapses, it is recommended to continue the use of UDCA for 3 months.

Effect on the ability to drive vehicles and mechanisms

UDCA does not have a negative effect on the ability to drive vehicles and/or other mechanisms.

Drug Interactions

When used concomitantly, antacids containing aluminum and ion-exchange resins (cholestyramine) reduce the absorption of UDCA.

When used concomitantly, hypolipidemic drugs (especially clofibrate), estrogens, neomycin, or progestogens (oral contraceptives) increase the saturation of bile with cholesterol and may reduce the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.

When used concomitantly, UDCA may increase the absorption of cyclosporine.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.