Rofecoxib

Teratogenic effects: Pregnancy Category C.

Rofecoxib was not teratogenic in rats at doses up to 50 mg/kg/day (approximately 28- and 10-fold human exposure at 25 and 50 mg daily based on AUC_0-24). There was a slight, non-statistically significant increase in the overall incidence of vertebral malformations only in the rabbit at doses of 50 mg/kg/day (approximately 1- or <1-fold human exposure at 25 and 50 mg daily based on AUC_0-24). There are no studies in pregnant women. Rofecoxib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Rofecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma. There was an increase in pup mortality and a decrease in pup body weight following exposure of pups to milk from dams administered rofecoxib during lactation. The dose tested represents approximately 18- and 6-fold human exposure at 25 and 50 mg based on AUC_0-24. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from rofecoxib, 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.

Rofecoxib was not carcinogenic in mice given oral doses up to 30 mg/kg (male) and 60 mg/kg (female) (approximately 5- and 2-fold the human exposure at 25 and 50 mg daily based on AUC_0-24) and in male and female rats given oral doses up to 8 mg/kg (approximately 6- and 2-fold the human exposure at 25 and 50 mg daily based on AUC_0-24) for two years.

Rofecoxib was not mutagenic in an Ames test or in a V-79 mammalian cell mutagenesis assay, nor clastogenic in a chromosome aberration assay in Chinese hamster ovary (CHO) cells, in an in vitro and an in vivo alkaline elution assay, or in an in vivo chromosomal aberration test in mouse bone marrow.

Rofecoxib did not impair male fertility in rats at oral doses up to 100 mg/kg (approximately 20- and 7-fold human exposure at 25 and 50 mg daily based on the AUC_0-24) and rofecoxib had no effect on fertility in female rats at doses up to 30 mg/kg (approximately 19- and 7-fold human exposure at 25 and 50 mg daily based on AUC_0-24).