Urcevel (Capsules) Instructions for Use

Marketing Authorization Holder

Velpharm, LLC (Russia)

ATC Code

A05AA02 (Ursodeoxycholic acid)

Active Substance

Ursodeoxycholic acid (Rec.INN registered by WHO)

Dosage Form

Urcevel

Capsules 250 mg: 5, 6, 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, 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.

Composition of the hard gelatin capsule: titanium dioxide, gelatin.

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

Hepatoprotector. Ursodeoxycholic acid is a bile acid. It reduces the cholesterol content in bile mainly by dispersing cholesterol and forming a liquid crystal phase. It affects the enterohepatic circulation of bile salts, reducing the reabsorption in the intestine 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 the content of bile acids in it. 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 larger or smaller amount of ursodeoxycholic acid accumulates in the bile. Under the action of intestinal bacteria, Ursodeoxycholic acid is partially destroyed 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

Take orally with a sufficient amount of water.

Swallow the capsule whole; do not chew or crush.

Administer the daily dose in two or three divided doses.

Take with meals to improve absorption and tolerability.

For dissolution of cholesterol gallstones, the typical dose is 10-12 mg/kg of body weight per day.

For primary biliary cholangitis (cirrhosis), the recommended dose is 13-15 mg/kg of body weight per day.

Divide the total daily dose for primary biliary cholangitis into four doses if possible.

For other cholestatic liver diseases, use a dose of 10-15 mg/kg per day.

For biliary reflux gastritis or esophagitis, use a dose of 250 mg once daily at bedtime.

Adjust the dose for pediatric patients based on body weight; follow specific pediatric dosing guidelines.

Continue treatment for gallstone dissolution for several months after stones have dissolved.

Perform ultrasound examinations at six-month intervals during gallstone dissolution therapy.

Monitor liver function tests (ALT, AST, ALP, GGT) regularly during therapy, especially during the first three months.

Do not use for the treatment of calcified gallstones or non-functioning gallbladder.

Discontinue treatment if biliary colic occurs frequently or if stones calcify during therapy.

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 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; children’s 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 possible only 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.

It can be used during breastfeeding if indicated, 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 case of unsuccessful portoenterostomy or in the absence of restoration of normal bile flow in children with biliary atresia.

It can be used in children 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 labels 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 dysfunction at an early stage. 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, 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 were very rarely observed. After discontinuation of therapy, partial regression of decompensation manifestations was noted.

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 it is necessary to use these agents simultaneously, they should be taken at least 2 hours before taking ursodeoxycholic acid.

With simultaneous use, Ursodeoxycholic acid may enhance 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 taking ursodeoxycholic acid has been described.

With simultaneous use, hypolipidemic 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.