Xgeva Use In Pregnancy & Lactation

Pregnancy: The safety and efficacy of XGEVA in pregnant women has not been established.
XGEVA is not recommended for use in pregnant women. Women should be advised not to become pregnant during and for at least 5 months after treatment with XGEVA.
At AUC exposures up to 16-fold higher than the human exposure (120 mg every 4 weeks), denosumab showed no evidence of impaired fertility in female cynomolgus monkeys.
In a study of cynomolgus monkeys dosed with denosumab during the period equivalent to the first trimester at AUC exposures up to 10-fold higher than the human dose (120 mg every 4 weeks), there was no evidence of maternal or fetal harm. In this study, fetal lymph nodes were not examined.
In another study of cynomolgus monkeys dosed with denosumab throughout pregnancy at AUC exposures 12-fold higher than the human dose (120 mg every 4 weeks), there were increased stillbirths and postnatal mortality; abnormal bone growth resulting in reduced bone strength, reduced hematopoiesis, and tooth malalignment; absence of peripheral lymph nodes; and decreased neonatal growth. There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. Maternal mammary gland development was normal.
Studies in mice suggest absence of RANKL during pregnancy may interfere with maturation of the mammary gland leading to impaired lactation post-partum.
Lactation: It is not known if denosumab is excreted in human milk. Because denosumab has the potential to cause adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug.