Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies were not conducted. Rifaximin was not genotoxic in the bacterial reverse mutation assay, chromosomal aberration assay, rat bone marrow micronucleus assay, and the CHO/HGPRT mutation assay. There was no effect on fertility in male or female rats following the administration of rifaximin at doses up to 300 mg/kg (approximately 5 times the clinical dose, adjusted for body surface area).
Pregnancy category C: Rifaximin was teratogenic in rats at doses of 150 to 300 mg/kg (approximately 2.5 to 5 times the clinical dose, adjusted for body surface area) and in rabbits at doses of 62.5 to 1000 mg/kg (approximately 2 to 33 times the clinical dose, adjusted for body surface area). These effects include cleft palate, agnatha, jaw shorterning, hemorrhage, eye partially open, small eyes, brachygnathia, incomplete ossification, and increased thoracolumbar vertebrae. There are no adequate and well controlled studies in pregnant women. XIFAXAN™ Tablets should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
Use during lactation
It is not known whether rifaximin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from XIFAXAN™ Tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
No specific information is available on the treatment of overdosage with XIFAXAN™ Tablets. In clinical studies at doses higher than the recommended dose (> 600 mg/day), adverse events were similar to the recommended dose (200 mg taken three times a day) and to placebo. In the case of overdosage, discontinue XIFAXAN™ Tablets, treat symptomatically, and institute supportive measures as required.