URSODIOL Drug Interactions: What You Need to Know

Drug Interactions Bile acid sequestering agents such as cholestyramine and colestipol may interfere with the action of ursodiol by reducing its absorption. Aluminum-based antacids have been shown to adsorb bile acids in vitro and may be expected to interfere with ursodiol in the same manner as the bile acid sequestering agents. Estrogens, oral contraceptives, and clofibrate (and perhaps other lipid-lowering drugs) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of ursodiol. Carcinogenesis, Mutagenesis, Impairment of Fertility Ursodeoxycholic acid was tested in 2-year oral carcinogenicity studies in CD-1 mice and Sprague-Dawley rats at daily doses of 50, 250, and 1,000 mg/kg/day. It was not tumorigenic in mice. In the rat study, it produced statistically significant dose-related increased incidences of pheochromocytomas of adrenal medulla in males (p = 0.014, Peto trend test) and females (p = 0.004, Peto trend test). A 78-week rat study employing intrarectal instillation of lithocholic acid and tauro-deoxycholic acid, metabolites of ursodiol and chenodiol, has been conducted. These bile acids alone did not produce any tumors. A tumor-promoting effect of both metabolites was observed when they were coadministered with a carcinogenic agent. Results of epidemiologic studies suggest that bile acids might be involved in the pathogenesis of human colon cancer in patients who had undergone a cholecystectomy, but direct evidence is lacking. Ursodiol is not mutagenic in the Ames test. Dietary administration of lithocholic acid to chickens is reported to cause hepatic adenomatous hyperplasia.

CONTRAINDICATIONS Ursodiol capsules will not dissolve calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones. Hence, patients with such stones are not candidates for ursodiol capsules therapy. Patients with compelling reasons for cholecystectomy including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula are not candidates for ursodiol capsules therapy. Allergy to bile acids.

AND PRECAUTIONS

• Abnormal Liver Function Tests : Liver function tests (γ-GT, alkaline phosphatase, AST, ALT) and bilirubin level should be monitored. Treatment discontinuation should be considered if parameters increase to a level considered clinically significant in patients with stable historical liver function test levels. Caution should be exercised to maintain patients’ bile flow. (5.1)
• Enteroliths in Patients with Risk for Intestinal Stenosis or Stasis: Monitor for obstructive gastrointestinal symptoms; if symptoms occur, hold ursodiol until a clinical evaluation has been conducted. ( 5.2 )

5.1 Abnormal Liver Function Tests Liver function tests ( y -GT, alkaline phosphatase, AST, ALT) and bilirubin levels should be monitored every month for three months after start of therapy, and every six months thereafter. This monitoring will allow the early detection of a possible deterioration of the hepatic function. Treatment discontinuation should be considered if the above parameters increase to a level considered clinically significant in patients with stable historical liver function test levels. Caution has to be exercised to maintain the bile flow of the patients taking ursodiol.

5.2 Enteroliths in Patients with Risk for Intestinal Stenosis or Stasis There have been rare postmarketing reports of Ursodiol tablets-treated patients who developed enteroliths (bezoars) resulting in obstructive symptoms that required surgical intervention. These patients had medical conditions that predisposed them to intestinal stenosis or stasis (e.g., surgical enteroanastomoses, Crohn's disease). If a patient presents with obstructive gastrointestinal symptoms, hold Ursodiol tablets until a clinical evaluation has been conducted.