Ursohil

• Approved Indications:
• Treatment of primary biliary cholangitis (PBC).
• Dissolution of small (<20 mm), non-calcified cholesterol gallstones in patients who are symptomatic and have a functioning gallbladder.
• Treatment of cholestasis in cystic fibrosis.
• Adjunct therapy for certain cholestatic liver diseases.
• Off-Label / Clinically Accepted Uses:
• Prevention and treatment of drug-induced cholestasis.
• Management of intrahepatic cholestasis of pregnancy (under specialist supervision).
• Treatment of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in select cases.
• Management of primary sclerosing cholangitis (limited evidence).

• Adults:
• Primary biliary cholangitis: 13-15 mg/kg/day orally in divided doses (usually twice daily).
• Gallstone dissolution: 8-10 mg/kg/day orally in divided doses; duration varies, typically 6 to 24 months.
• Cholestasis of cystic fibrosis: 10-15 mg/kg/day orally, divided doses.
• Pediatrics:
• Dosing adjusted by body weight, commonly 10-15 mg/kg/day orally in divided doses.
• Use under specialist supervision.
• Elderly:
• Same as adults; adjust dose based on clinical response and tolerability.
• Special Populations:
• Hepatic impairment: Use cautiously; no specific dose adjustment but monitor liver function.
• Renal impairment: No dose adjustment necessary.
• Route:
• Oral (tablets or capsules).
• Duration:
• Chronic conditions often require long-term treatment; gallstone dissolution may require months to years.

Ursodeoxycholic acid is a hydrophilic bile acid that reduces the cytotoxicity of hydrophobic bile acids by displacing them in the bile acid pool. It promotes bile flow (choleresis), stabilizes hepatocyte membranes, protects cholangiocytes against cytotoxicity, and modulates immune-mediated liver damage. Ursodeoxycholic acid also reduces cholesterol absorption and secretion into bile, aiding in gallstone dissolution by decreasing cholesterol saturation.

• Absorption:
• Well absorbed orally with bioavailability around 60-80%.
• Distribution:
• Undergoes enterohepatic circulation; distributed primarily in bile and liver tissues.
• Metabolism:
• Partially metabolized in the liver to lithocholic acid and other bile acids.
• Elimination:
• Excreted mainly via bile into feces; minimal renal excretion.
• Half-life:
• Approximately 3.5 to 5.8 days due to enterohepatic recirculation.
• Onset of Action:
• Therapeutic effects typically develop over weeks to months.

• Pregnancy:
• FDA Category B.
• Animal studies have not demonstrated risk; limited human data suggest cautious use when clearly indicated.
• Lactation:
• Ursodeoxycholic acid is excreted in breast milk in small amounts.
• Use during breastfeeding only if benefits outweigh potential risks.

• Hepatobiliary agent
• Bile acid
• Choleretic agent

• Known hypersensitivity to ursodeoxycholic acid or any formulation components.
• Acute cholecystitis or biliary obstruction without decompression.
• Gallstones with high calcium content or calcified stones.
• Severe liver dysfunction where bile secretion is severely impaired.

• Monitor liver function tests regularly during therapy.
• Use cautiously in patients with cirrhosis or advanced liver disease.
• Discontinue if worsening liver function or severe adverse reactions occur.
• Not effective for pigment stones or radiopaque gallstones.
• Avoid abrupt discontinuation in chronic liver disease.

• Common:
• Diarrhea or loose stools.
• Abdominal discomfort or bloating.
• Less Common:
• Nausea, vomiting.
• Headache, dizziness.
• Rare:
• Rash, pruritus, urticaria.
• Elevated liver enzymes or hepatotoxicity (rare).
• Side effects are generally mild and dose-dependent.

• May reduce absorption of fat-soluble vitamins (A, D, E, K) with long-term use.
• Cholestyramine and colestipol reduce absorption of ursodeoxycholic acid; administer several hours apart.
• Rifampicin may decrease ursodeoxycholic acid levels by inducing metabolism.
• No major CYP450-mediated interactions; minimal systemic metabolism.

• Updated guidelines for primary biliary cholangitis recommend ursodeoxycholic acid as first-line therapy.
• Recent studies explore use in nonalcoholic fatty liver disease with mixed outcomes.
• No major changes in dosing or safety warnings from FDA, EMA, or WHO in recent years.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Do not freeze.
• Keep out of reach of children.