ACTIGALL Capsule Ref.[50738] Active ingredients: Ursodeoxycholic acid

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

The following tables provide comprehensive listings of the adverse experiences reported that occurred with a 5% incidence level:

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 Actigall therapy and, in fact, Actigall has been shown to decrease liver enzyme levels in liver disease. However, patients given Actigall should have SGOT (AST) and SGPT (ALT) measured at the initiation of therapy and thereafter as indicated by the particular clinical circumstances.

Bile acid sequestering agents such as cholestyramine and colestipol may interfere with the action of Actigall by reducing its absorption. Aluminum-based antacids have been shown to adsorb bile acids in vitro and may be expected to interfere with Actigall in the same manner as the bile acid sequestering agents. Estrogens, oral contraceptives, and clofibrate (and perhaps other lipidlowering drugs) increase hepatic cholesterol secretion, and encourage cholesterol gallstone formation and hence may counteract the effectiveness of Actigall.

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 Actigall 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.

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

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

In worldwide clinical studies of Actigall, 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 Actigall cannot be ruled out. Therefore, it is recommended that dosing proceed with caution in this population.