Ursoxynol (Capsules) Instructions for Use

Marketing Authorization Holder

Veltrade, LLC (Russia)

Manufactured By

Velpharm, LLC (Russia)

ATC Code

A05AA02 (Ursodeoxycholic acid)

Active Substance

Ursodeoxycholic acid (Rec.INN registered by WHO)

Dosage Form

Ursoxynol

Capsules 250 mg: 10, 12, 15, 18, 20, 24, 25, 30, 35, 36, 40, 42, 45, 48, 50, 54, 60, 70, 75, 80, 90, 100, 105, 120, 125, 135, 140, 150, 160, 175, 180, 200, 225 or 250 pcs.

Dosage Form, Packaging, and Composition

Capsules hard, gelatin, size No. 0, white; capsule contents – white or almost white powder.

Excipients: corn starch, colloidal silicon dioxide (aerosil), magnesium stearate.

Gelatin capsule composition: titanium dioxide, gelatin.

5 pcs. – blister packs (1) – cardboard packs.
5 pcs. – blister packs (2) – cardboard packs.
5 pcs. – blister packs (3) – cardboard packs.
5 pcs. – blister packs (4) – cardboard packs.
5 pcs. – blister packs (5) – cardboard packs.
5 pcs. – blister packs (6) – cardboard packs.
5 pcs. – blister packs (7) – cardboard packs.
5 pcs. – blister packs (8) – cardboard packs.
5 pcs. – blister packs (9) – cardboard packs.
5 pcs. – blister packs (10) – cardboard packs.
6 pcs. – blister packs (1) – cardboard packs.
6 pcs. – blister packs (2) – cardboard packs.
6 pcs. – blister packs (3) – cardboard packs.
6 pcs. – blister packs (4) – cardboard packs.
6 pcs. – blister packs (5) – cardboard packs.
6 pcs. – blister packs (6) – cardboard packs.
6 pcs. – blister packs (7) – cardboard packs.
6 pcs. – blister packs (8) – cardboard packs.
6 pcs. – blister packs (9) – cardboard packs.
6 pcs. – blister packs (10) – cardboard packs.
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 (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.
10 pcs. – blister packs (7) – cardboard packs.
10 pcs. – blister packs (8) – cardboard packs.
10 pcs. – blister packs (9) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.
15 pcs. – blister packs (1) – cardboard packs.
15 pcs. – blister packs (2) – cardboard packs.
15 pcs. – blister packs (3) – cardboard packs.
15 pcs. – blister packs (4) – cardboard packs.
15 pcs. – blister packs (5) – cardboard packs.
15 pcs. – blister packs (6) – cardboard packs.
15 pcs. – blister packs (7) – cardboard packs.
15 pcs. – blister packs (8) – cardboard packs.
15 pcs. – blister packs (9) – cardboard packs.
15 pcs. – blister packs (10) – cardboard packs.
20 pcs. – blister packs (1) – cardboard packs.
20 pcs. – blister packs (2) – cardboard packs.
20 pcs. – blister packs (3) – cardboard packs.
20 pcs. – blister packs (4) – cardboard packs.
20 pcs. – blister packs (5) – cardboard packs.
20 pcs. – blister packs (6) – cardboard packs.
20 pcs. – blister packs (7) – cardboard packs.
20 pcs. – blister packs (8) – cardboard packs.
20 pcs. – blister packs (9) – cardboard packs.
20 pcs. – blister packs (10) – cardboard packs.
25 pcs. – blister packs (1) – cardboard packs.
25 pcs. – blister packs (2) – cardboard packs.
25 pcs. – blister packs (3) – cardboard packs.
25 pcs. – blister packs (4) – cardboard packs.
25 pcs. – blister packs (5) – cardboard packs.
25 pcs. – blister packs (6) – cardboard packs.
25 pcs. – blister packs (7) – cardboard packs.
25 pcs. – blister packs (8) – cardboard packs.
25 pcs. – blister packs (9) – cardboard packs.
25 pcs. – blister packs (10) – cardboard packs.
10 pcs. – jars – cardboard packs.
20 pcs. – jars – cardboard packs.
30 pcs. – jars – cardboard packs.
40 pcs. – jars – cardboard packs.
50 pcs. – jars – cardboard packs.
60 pcs. – jars – cardboard packs.
70 pcs. – jars – cardboard packs.
80 pcs. – jars – cardboard packs.
90 pcs. – jars – cardboard packs.
100 pcs. – jars – cardboard packs.

Clinical-Pharmacological Group

Hepatoprotective agent with choleretic and cholelitholytic action

Pharmacotherapeutic Group

Drugs for the treatment of liver and biliary tract diseases; drugs for the treatment of biliary tract diseases; bile acid preparations

Pharmacological Action

Hepatoprotector. Ursodeoxycholic acid is a bile acid. It reduces the cholesterol content in bile mainly by dispersing cholesterol and forming a liquid crystalline 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 of no more than 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 taking 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. Swallow the capsules whole with a sufficient amount of water.

Take the daily dose in the evening, as a single administration.

For dissolution of cholesterol gallstones, the recommended dose is 10-12 mg/kg of body weight per day. Divide the total daily dose into two or three administrations if necessary.

For primary biliary cholangitis (cirrhosis), the recommended dose is 13-15 mg/kg of body weight per day. Divide the total daily dose into two to four administrations throughout the day.

For chronic hepatitis with cholestasis and biliary reflux gastritis/esophagitis, the recommended dose is 10-15 mg/kg of body weight per day. Divide the total daily dose into two or three administrations.

For cystic fibrosis and other cholestatic liver diseases in pediatric patients, the recommended dose is 20-30 mg/kg of body weight per day. Divide the total daily dose into two or three administrations.

For symptomatic treatment of biliary dyspepsia, the recommended dose is 250 mg once daily in the evening for 10 to 14 days. Treatment duration may be extended up to several months based on clinical response.

Adjust the dose individually based on the patient’s body weight and the specific indication. Regularly monitor liver function tests (ALT, AST, ALP, GGT) during therapy, especially during the first three months of treatment.

For gallstone dissolution, confirm the presence of radiolucent, non-calcified stones in a functioning gallbladder prior to initiating therapy. Continue treatment for several months after confirmed stone dissolution.

Discontinue treatment if calcification of stones is detected during follow-up examinations or if recurrent biliary colic persists.

Adverse Reactions

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

From the liver and biliary tract: very rarely – calcification of gallstones, during treatment of advanced stages of primary biliary cirrhosis – decompensation of liver cirrhosis, which disappears 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, liver cirrhosis in the stage of decompensation, 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 no restoration of 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 according to indications, in recommended doses.

Use in Hepatic Impairment

Contraindicated in some liver diseases.

Use in Renal Impairment

Contraindicated in severe renal failure.

Pediatric Use

Contraindicated for use in cases of unsuccessful portoenterostomy or in the absence of restoration of normal bile flow in children with biliary atresia.

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

Special Precautions

Treatment with ursodeoxycholic acid should be carried out under medical supervision. During the first 3 months of treatment, liver function parameters should be monitored: transaminases, ALP and GGT in blood serum every 4 weeks, and then every 3 months. Monitoring these parameters allows for the detection of liver function disorders at early stages. 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 timely detection of signs of stone calcification depending on their size, the gallbladder should be visualized (oral cholecystography) with examination of shadows in 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, weak 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, lipid-lowering drugs (especially clofibrate), estrogens, neomycin, or progestins increase the saturation of bile with cholesterol 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.