Pregnancy: There are no adequate data from the use of XGEVA in pregnant women. Reproductive toxicity was shown in a study of cynomolgus monkeys, dosed throughout pregnancy with denosumab at AUC exposures 12-fold higher than the human dose (see Pharmacology: Toxicology: Preclinical safety data under Actions).
XGEVA is not recommended for use in pregnant women and women of childbearing potential not using contraception. Women should be advised not to become pregnant during and for at least 5 months after treatment with XGEVA. Any effects of XGEVA are likely to be greater during the second and third trimesters of pregnancy since monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester.
Breast-feeding: It is unknown whether denosumab is excreted in human milk. A risk to the newborns/infants cannot be excluded. Knockout mouse studies suggest absence of RANKL during pregnancy may interfere with maturation of the mammary gland leading to impaired lactation post-partum (see Pharmacology: Toxicology: Preclinical safety data under Actions). A decision must be made on whether to abstain from breast-feeding or to abstain from XGEVA therapy taking into account the benefit of breast-feeding to the newborn/infant and the benefit of therapy for the woman.
Fertility: No data are available on the effect of denosumab on human fertility. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).