See Full Prescribing Information

Please see Full Prescribing Information and Important Safety Information on the product itself or by clicking here.

Individual patient results may vary. To report suspected adverse reactions, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also contact Pangea Pharmaceuticals at 855-892-8224 or drugsafety@pangeapharm.com.

Indications & Usage

• Ursolign™ is indicated for patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. Safety of use of Ursolign™ beyond 24 months is not established.
• Ursolign™ is indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss.

Contraindications

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

How Supplied

Ursolign™ 150 mg is white to off-white granular powder filled in size '3' hard gelatin capsule with white cap imprinted with "UD" and white body imprinted with "150". Bottle of 60 Capsules with child-resistant closure: NDC 81279-130-60.

Warnings

Enteroliths in Patients with Risk for Intestinal Stenosis or Stasis

There have been rare postmarketing reports of ursodiol-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 Ursolign™ until a clinical evaluation has been conducted.

Precautions

Liver Tests

Ursodiol therapy has not been associated with liver damage. Lithocholic acid, a naturally occurring bile acid, is known to be a liver-toxic metabolite. This bile acid is formed in the gut from ursodiol less efficiently and in smaller amounts than that seen from chenodiol. Lithocholic acid is detoxified in the liver by sulfation and, although man appears to be an efficient sulfater, it is possible that some patients may have a congenital or acquired deficiency in sulfation, thereby predisposing them to lithocholate-induced liver damage.

Abnormalities in liver enzymes have not been associated with Ursolign™ therapy and, in fact, Ursolign™ has been shown to decrease liver enzyme levels in liver disease. However, patients given Ursolign™ should have SGOT (AST) and SGPT (ALT) measured at the initiation of therapy and thereafter as indicated by the particular clinical circumstances.

Warnings (con't)

Drug Interactions

Bile acid sequestering agents such as cholestyramine and colestipol may interfere with the action of Ursolign™ by reducing its absorption. Aluminum-based antacids have been shown to adsorb bile acids in vitro and may be expected to interfere with Ursolign™ 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 Ursolign™.

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 1000 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 co-administered 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.

Pregnancy

Reproduction studies have been performed in rats and rabbits with ursodiol doses up to 200-fold the therapeutic dose and have revealed no evidence of impaired fertility or harm to the fetus at doses of 20- to 100-fold the human dose in rats and at 5-fold the human dose (highest dose tested) in rabbits. Studies employing 100- to 200-fold the human dose in rats have shown some reduction in fertility rate and litter size. There have been no adequate and well-controlled studies of the use of ursodiol in pregnant women, but inadvertent exposure of 4 women to therapeutic doses of the drug in the first trimester of pregnancy during the Ursolign™ trials led to no evidence of effects on the fetus or newborn baby. Although it seems unlikely, the possibility that ursodiol can cause fetal harm cannot be ruled out; hence, the drug is not recommended for use during pregnancy.

Nursing Mothers

It is not known whether ursodiol is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Ursolign™ is administered to a nursing mother.

Pediatric Use

The safety and effectiveness of Ursolign™ in pediatric patients have not been established.

Geriatric Use

In worldwide clinical studies of Ursolign™, approximately 14% of subjects were over 65 years of age (approximately 3% were over 75 years old). In a subgroup analysis of existing clinical trials, patients greater than 56 years of age did not exhibit statistically significantly different complete dissolution rates from the younger population. No age-related differences in safety and effectiveness were found. Other reported clinical experience has not identified differences in response in elderly and younger patients. However, small differences in efficacy and greater sensitivity of some elderly individuals taking Ursolign™ cannot be ruled out. Therefore, it is recommended that dosing proceed with caution in this population.

Adverse Reactions

The nature and frequency of adverse experiences were similar across all groups.

Please refer to the Prescribing Information for a full table that provides comprehensive listings of the adverse experiences reported that occurred with a 5% incidence level.