Ursoliv® capsules 250 mg

Instructions for use Ursoliv® capsules 250 mg

Trade name of the drug: Ursoliv^®

International nonproprietary name: Ursodeoxycholic acid

Dosage form: capsules.

Composition per one capsule:

Active substance: ursodeoxycholic acid 250.0 mg.

Excipients: lactulose 300.0 mg, talc 18.0 mg, microcrystalline cellulose 102 up to a capsule content weight of 600.0 mg.

Hard gelatin capsules:

• body: colorant azorubine (E 122) 0.05 %, titanium dioxide 1.00 %, gelatin up to 100 %.
• cap: colorant azorubine (E 122) 0.05 %, titanium dioxide 1.00 %, gelatin up to 100 %.

Description:

Size No. 00 hard gelatin capsules with a pink body and cap. The capsule contents are a granulated white or almost white powder.

Pharmacotherapeutic group: hepatoprotective agent

ATC code:  A05AA02

Pharmacological action   

Pharmacodynamics

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 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. It increases the solubility of cholesterol in the biliary system. Causes partial or complete dissolution of cholesterol gallstones upon enteral administration, reduces the cholesterol saturation of bile.

Stimulates the formation and secretion of bile, accelerates the excretion of toxic bile acids through the intestines. Upon oral administration, the proportion of UDCA in the total bile acid pool increases significantly; UDCA competes with other bile acids during absorption in the small intestine, as well as during penetration through the hepatocyte membrane, which leads to reduced absorption of toxic bile acids in the intestine and their entry into the liver, preventing their cytopathogenic effect.

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.

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

Pharmacokinetics

UDCA is absorbed in the small intestine (about 90%), with the maximum plasma concentration (C_max) after oral administration of a 250 mg dose being about 3.3 µg/ml, and the time to reach maximum concentration is about 2 hours.

Protein binding of unconjugated UDCA in healthy individuals is at least 70%. 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 30 to 50% of the total bile acids in the blood. The therapeutic effect of the drug depends on the concentration of UDCA in the bile.

Metabolized in the liver, converting into taurine and glycine conjugates, which are secreted into the bile. About 50-70% of the orally administered dose is excreted in the bile. Urinary excretion 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 for use

• Dissolution of cholesterol gallstones in the gallbladder;
• Biliary reflux gastritis;
• Primary biliary cirrhosis in the absence of signs of decompensation;
• Chronic hepatitis of various origins;
• Primary sclerosing cholangitis;
• Cystic fibrosis (as part of combination therapy);
• Non-alcoholic steatohepatitis;
• Alcoholic liver disease;
• Biliary dyskinesia.

Contraindications

Radiopaque (high calcium content) gallstones; impaired contractility of the gallbladder, biliary tract obstruction (obstruction of the common bile duct or cystic duct); frequent episodes of biliary colic; acute inflammatory diseases of the gallbladder and bile ducts; decompensated liver cirrhosis; severe hepatic and/or renal failure; hypersensitivity to the components of the drug or other bile acids.

Pediatric population

Unsuccessful portoenterostomy or cases without restoration of normal bile flow in children with biliary atresia. Children under three years of age, patients who have difficulty swallowing solid dosage forms.

Dosage and administration

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

Dissolution of cholesterol gallstones:

Capsules are taken in the evening, before going to bed, with a sufficient amount of liquid. Approximately 10 mg per 1 kg of body weight daily, which corresponds to:

• 2 capsules of Ursoliv^® for patients weighing up to 60 kg;
• 3 capsules of Ursoliv^® for patients weighing up to 80 kg;
• 4 capsules of Ursoliv^® for patients weighing up to 100 kg;
• 5 capsules of Ursoliv^® for patients weighing over 100 kg.

Duration of treatment 6–12 months.

To prevent stone recurrence, it is recommended to take the drug for several more months after stone dissolution.

Symptomatic treatment of primary biliary cirrhosis:

The daily dose depends on body weight and ranges from 2 to 6 capsules (approximately 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.

Recommended dosing schedule:

Body weight	Daily dose	Morning	Afternoon	Evening
34-50 kg	2 capsules	1	-	1
51-65 kg	3 capsules	1	1	1
66-85 kg	4 capsules	1	1	2
86-110 kg	5 capsules	1	2	2
Over 110 kg	6 capsules	2	2	2

For the treatment of biliary reflux gastritis:

1 capsule once a day before bedtime.

Course of treatment - from 10–14 days to 6 months, if necessary – up to 2 years.

For chronic hepatitis of various origins (toxic, drug-induced, etc.), non-alcoholic fatty liver disease, incl. non-alcoholic steatohepatitis, alcoholic liver disease:

Average daily dose — 10–15 mg/kg in 2–3 divided doses. Duration of therapy — 6–12 months or longer.

For primary sclerosing cholangitis, cystic fibrosis (mucoviscidosis):

Average daily dose — 12–15 mg/kg; if necessary, the average daily dose can be increased to 20–30 mg/kg in 2–3 divided doses. Duration of therapy — from 6 months to several years.

For biliary dyskinesia of the hypokinetic type:

Average daily dose — 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

Gastrointestinal disorders: nausea, vomiting, pain in the epigastric area and right hypochondrium, constipation, transient increase in the activity of "liver" transaminases; rarely - diarrhea (may be dose-dependent), calcification of gallstones.

During treatment of primary biliary cirrhosis, transient decompensation of liver cirrhosis may be observed, which disappears after discontinuation of the drug.

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

Overdose

Cases of UDCA overdose have not been described to date. The most likely manifestation of severe overdose would be diarrhea, which should be treated symptomatically.

Drug interactions

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

Concomitant use of hypolipidemic drugs (especially clofibrate), estrogens, neomycin, or progestogens (oral contraceptives) increases the cholesterol saturation of bile and may reduce the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.

Concomitant use of UDCA may increase the absorption of cyclosporine.

Special instructions

For the dissolution of gallstones using UDCA, the concretions must be cholesterol-based (non-radiopaque), sized no more than 15-20 mm. The gallbladder must remain functional, and the patency of the cystic and common bile ducts must be preserved.

When prescribed for gallstone dissolution, monthly (and subsequently every 3 months) biochemical blood tests should be performed to determine the activity of "liver" transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin concentration. If elevated levels persist, the drug should be discontinued.

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

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

After complete stone dissolution, to prevent recurrence, it is recommended to continue the use of ursodeoxycholic acid for 3 months.

Effect on ability to drive and operate machinery

The drug does not negatively affect the ability to drive vehicles and/or operate machinery.

Dosage form

Capsules 250 mg.

10 capsules in a blister strip made of polyvinyl chloride film and printed lacquered aluminum foil.

1, 2, 3, 5 or 10 blister packs, together with the instructions for use, are placed in a cardboard carton for consumer packaging.

Storage conditions

Store in a dry place, protected from light and moisture, at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf life

4 years. Do not use after the expiration date.

Prescription status

By prescription.

Name and address of the legal entity in whose name the registration certificate is issued:

JSC "AVVA RUS", Russia, 121614, 

Moscow, Krylatskie Kholmy st., 30, building 9

tel.: +7 (495) 956-75-54

avva.com.ru

Manufacturer/Organization accepting consumer claims:

JSC "AVVA RUS", Russia,

610044, Kirov region, Kirov, Luganskaya st., 53a.

Tel.: +7 (8332) 25-12-29; +7 (495) 956-75-54.

avva.com.ru