Ursodiolisin (Capsules) Instructions for Use

Marketing Authorization Holder

Marbiopharm, JSC (Russia)

ATC Code

A05AA02 (Ursodeoxycholic acid)

Active Substance

Ursodeoxycholic acid (Rec.INN WHO registered)

Dosage Form

Ursodiolisin

Capsules 250 mg: 50, 60, 90 or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard, opaque, gelatin, size No. 0, white or almost white; the capsule contents are a mixture of powder and granules, white or almost white.

Excipients: corn starch – 68 mg, anhydrous colloidal silicon dioxide (aerosil) – 5 mg, magnesium stearate – 2 mg.

Composition of the hard gelatin capsule shell: titanium dioxide – from 0 to 2.88, medical gelatin – up to 96.

10 pcs. – blister packs (PVC/aluminum foil) (6) – cartons.
10 pcs. – blister packs (PVC/aluminum foil) (10) – cartons.
15 pcs. – blister packs (PVC/aluminum foil) (4) – cartons.
15 pcs. – blister packs (PVC/aluminum foil) (6) – cartons.
50 pcs. – polyethylene jars (1) – cartons.
100 pcs. – polyethylene jars (1) – cartons.

Clinical-Pharmacological Group

Hepatoprotective agent with choleretic and cholelitholytic action

Pharmacotherapeutic Group

Hepatoprotective agent

Pharmacological Action

Hepatoprotector. Ursodeoxycholic acid is a bile acid. It reduces the cholesterol content in bile, primarily by dispersing cholesterol and forming a liquid crystal phase. It affects the enterohepatic circulation of bile salts, reducing the intestinal reabsorption of endogenous, more hydrophobic and potentially toxic compounds.

In vitro studies have shown that Ursodeoxycholic acid has a direct hepatoprotective effect and reduces the hepatotoxicity of hydrophobic bile salts.

It affects immunological reactions by reducing the pathological expression of HLA class I antigens on hepatocytes and suppressing the production of cytokines and interleukins.

Ursodeoxycholic acid reduces the lithogenic index of bile by increasing its bile acid content. It promotes partial or complete dissolution of cholesterol gallstones when taken orally. It has a choleretic effect.

Pharmacokinetics

After oral administration, Ursodeoxycholic acid is rapidly absorbed in the jejunum and the proximal part of the ileum by passive diffusion, and in the distal part of the ileum by active transport. Approximately 60-80% is absorbed.

After absorption, the bile acid is almost completely conjugated in the liver with glycine and taurine and excreted in the bile. Up to 60% is metabolized during the first pass through the liver.

Depending on the daily dose, the type of disease, or the condition of the liver, a greater or lesser amount of ursodeoxycholic acid accumulates in the bile. Under the action of intestinal bacteria, Ursodeoxycholic acid is partially broken down to form 7-keto-lithocholic and lithocholic acids.

The T_1/2 of ursodeoxycholic acid is 3.5-5.8 days.

Indications

Cholesterol gallstones in the gallbladder and common bile duct in patients when surgical or endoscopic treatment is not possible. Cholesterol stones of the gallbladder and common bile duct with a diameter not exceeding 1.5-2 cm after extracorporeal lithotripsy or mechanical lithotripsy. Primary biliary cirrhosis (before the formation of advanced fibrosis and cirrhotic transformation of the liver). Chronic active hepatitis with cholestatic syndrome. Acute hepatitis, cystic fibrosis, congenital biliary atresia. Biliary reflux esophagitis and gastritis. Biliary dyspeptic syndrome in cholecystopathy and biliary dyskinesia. Prevention and treatment of cholestatic syndrome caused by the use of hormonal contraceptives. To normalize liver function in patients receiving cytostatic therapy, as well as in patients with alcoholic liver disease, non-alcoholic steatohepatitis. Liver and other organ transplantation (adjuvant treatment).

ICD codes

Dosage Regimen

Administer orally. The daily dose is 10-15 mg/kg of body weight for most indications, including gallstone dissolution and cholestatic liver diseases.

For gallstone dissolution, take the total daily dose once daily at bedtime or divide it into two or three doses throughout the day. Continue treatment for several months after stone dissolution, confirmed by two consecutive ultrasound examinations.

For primary biliary cholangitis (cirrhosis), the standard dose is 13-15 mg/kg/day, administered in divided doses. Treatment is long-term.

For cholestatic syndrome in children with cystic fibrosis or biliary atresia, the dose is 20-30 mg/kg/day in two to three divided doses.

For biliary reflux gastritis or esophagitis, take 250 mg once daily at bedtime for 10-14 days, with possible extension to 6 months.

For alcoholic liver disease or non-alcoholic steatohepatitis, the dose is 10-15 mg/kg/day in divided doses for several months.

For prevention of hepatotoxicity during cytostatic therapy, use 8-10 mg/kg/day in divided doses.

Swallow capsules whole with a sufficient amount of water. Do not crush or chew.

Take the drug regularly. For divided doses, take with meals. For a single bedtime dose, take after the evening meal.

Monitor liver function tests (ALT, AST, ALP, GGT) every 4 weeks for the first 3 months, then every 3 months.

For gallstone dissolution, perform ultrasound control 6-10 months after starting treatment and every 6 months thereafter.

In case of diarrhea, reduce the dose. Discontinue treatment if diarrhea persists.

Adverse Reactions

From the digestive system: frequently – unformed stools or diarrhea; very rarely, when treating primary biliary cirrhosis – acute pain in the right upper abdomen.

From the liver and biliary tract: very rarely – calcification of gallstones; when treating advanced stages of primary biliary cirrhosis – decompensation of liver cirrhosis, which resolves after discontinuation of ursodeoxycholic acid.

From the skin and subcutaneous tissues: very rarely – allergic reactions, urticaria.

Contraindications

Hypersensitivity to ursodeoxycholic acid and other bile acids; X-ray positive (high calcium content) gallstones, impaired contractility of the gallbladder, acute inflammatory diseases of the gallbladder and bile ducts, decompensated liver cirrhosis, severe hepatic and/or renal failure, occlusion of the biliary tract (occlusion of the common bile duct or cystic duct), frequent episodes of biliary colic; unsuccessful portoenterostomy or cases of failure to restore normal bile flow in children with biliary atresia; pediatric age – depending on the dosage form.

Use in Pregnancy and Lactation

Ursodeoxycholic acid should not be used during pregnancy.

Use of the drug by women of childbearing potential is only possible if they use reliable methods of contraception. It is recommended to use non-hormonal contraceptives or oral contraceptives with low estrogen content, since hormonal oral contraceptives may enhance gallstone formation. Before starting treatment, possible pregnancy should be excluded.

Use during breastfeeding is possible if indicated, at recommended doses.

Use in Hepatic Impairment

Contraindicated in some liver diseases.

Use in Renal Impairment

Contraindicated in severe renal failure.

Pediatric Use

Contraindicated in cases of unsuccessful portoenterostomy or failure to restore normal bile flow in children with biliary atresia.

Use in children is possible if indicated, in age- and body weight-appropriate doses and dosage forms. It is necessary to strictly follow the instructions in the ursodeoxycholic acid drug labels regarding contraindications for the use of specific dosage forms of ursodeoxycholic acid in children of different ages.

Special Precautions

Treatment with ursodeoxycholic acid should be carried out under medical supervision. During the first 3 months of treatment, liver function tests should be monitored: transaminases, ALP and GGT in blood serum every 4 weeks, and then every 3 months. Monitoring these parameters allows for the early detection of liver function impairment. This also applies to patients in the late stages of primary biliary cirrhosis. Furthermore, this allows for quick determination of whether a patient with primary biliary cirrhosis is responding to the treatment.

When using ursodeoxycholic acid to dissolve cholesterol gallstones, in order to assess treatment progress and for the timely detection of signs of stone calcification depending on their size, the gallbladder should be visualized (oral cholecystography) with examination of opacities in the standing and supine positions (ultrasound) 6-10 months after the start of treatment. If the gallbladder cannot be visualized on X-rays or in cases of stone calcification, poor gallbladder contractility, or frequent colic attacks, ursodeoxycholic acid should not be used.

When treating patients in the late stages of primary biliary cirrhosis, cases of decompensation of liver cirrhosis have been very rarely reported. After discontinuation of therapy, partial regression of decompensation manifestations was observed.

In patients with diarrhea, the dose of ursodeoxycholic acid should be reduced. If diarrhea persists, treatment should be discontinued.

Drug Interactions

With simultaneous use, cholestyramine, colestipol, and antacids containing aluminum hydroxide or smectite (aluminum oxide) reduce the absorption of ursodeoxycholic acid in the intestine and thus reduce its effectiveness. If simultaneous use of these agents is necessary, they should be taken at least 2 hours before taking ursodeoxycholic acid.

With simultaneous use, Ursodeoxycholic acid may increase the absorption of cyclosporine from the intestine. The concentration of cyclosporine in the blood should be monitored and its dose adjusted if necessary when using this combination.

A case of decreased plasma concentration of ciprofloxacin in a patient receiving ursodeoxycholic acid has been described.

With simultaneous use, hypolipidemic drugs (especially clofibrate), estrogens, neomycin, or progestins increase the cholesterol saturation of bile and may reduce the ability of ursodeoxycholic acid to dissolve cholesterol gallstones.

With simultaneous use, Ursodeoxycholic acid reduces the C_max and AUC of nitrendipine. An increase in the dose of nitrendipine may be required.

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.