No information provided.

Patients with variceal bleeding, hepatic encephalopathy, ascites or in need of an urgent liver transplant, should receive appropriate specific treatment.

Carcinogenicity, Mutagenicity and Impairment of Fertility

In two 24-month oral carcinogenicity studies in mice, ursodiol at doses up to 1,000 mg/kg/day (3,000 mg/m²/day) was not tumorigenic. Based on body surface area, for a 50 kg person of average height (1.46 m² body surface area), this dose represents 5.4 times the recommended maximum clinical dose of 15 mg/kg/day (555 mg/m²/day).

In a two-year oral carcinogenicity study in Fischer 344 rats, ursodiol at doses up to 300 mg/kg/day (1,800 mg/m²/day, 3.2 times the recommended maximum human dose based on body surface area) was not tumorigenic.

In a life-span (126-138 weeks) oral carcinogenicity study, Sprague-Dawley rats were treated with doses of 33 to 300 mg/kg/day, 0.4 to 3.2 times the recommended maximum human dose based on body surface area. Ursodiol produced a significantly (p < 0.5, Fisher's exact test) increased incidence of pheochromocytomas of the adrenal medulla in females of the highest dose group.

In 103-week oral carcinogenicity studies of lithocholic acid, a metabolite of ursodiol, doses up to 250 mg/kg/day in mice and 500 mg/kg/day in rats did not produce any tumors. In a 78-week rat study, intrarectal instillation of lithocholic acid (1 mg/kg/day) for 13 months did not produce colorectal tumors. A tumor-promoting effect was observed when it was administered after a single intrarectal dose of a known carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. On the other hand, in a 32-week rat study, ursodiol at a daily dose of 240 mg/kg (1,440 mg/m², 2.6 times the maximum recommended human dose based on body surface area) suppressed the colonic carcinogenic effect of another known carcinogen azoxymethane.

Ursodiol was not genotoxic in the Ames test, the mouse lymphoma cell (L5178Y, TK^+/-) forward mutation test, the human lymphocyte sister chromatid exchange test, the mouse spermatogonia chromosome aberration test, the Chinese hamster micronucleus test and the Chinese hamster bone marrow cell chromosome aberration test.

Ursodiol at oral doses of up to 2,700 mg/kg/day (16,200 mg/m²/day, 29 times the recommended maximum human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

Pregnancy, Teratogenic Effects. Pregnancy Category B

Teratology studies have been performed in pregnant rats at oral doses up to 2,000 mg/kg/day (12,000 mg/m²/day, 22 times the recommended maximum human dose based on body surface area) and in pregnant rabbits at oral doses up to 300 mg/kg/day (3,600 mg/m²/day, 7 times the recommended maximum human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to ursodiol.

There are no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

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 URSO 250® and URSO Forte® are administered to a nursing mother.

Pediatric Use

The safety and effectiveness of URSO 250® and URSO Forte® in pediatric patients have not been established.

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