Pregnancy: There is no adequate data in pregnant women. Denosumab (Prolia) is not recommended for use in pregnant women. At AUC exposures up to 100-fold higher than the human exposure (60 mg every 6 months), denosumab showed no evidence of impaired fertility or harm to the foetus in cynomolgus monkeys (see Pharmacology: Toxicology: Pre-Clinical Safety Data under Actions).
In a study of cynomolgus monkeys dosed with Denosumab during the period equivalent to the first trimester at AUC exposures up to 99-fold higher than the human dose (60 mg every 6 months), there was no evidence of maternal or foetal harm. In this study, foetal lymph nodes were not examined.
In another study of cynomolgus monkeys dosed with Denosumab throughout pregnancy at AUC exposures 119-fold higher than the human dose (60 mg every 6 months), there were increased stillbirths and postnatal mortality; abnormal bone growth resulting in reduced bone strength, reduced haematopoiesis, and tooth malalignment; absence of peripheral lymph nodes; and decreased neonatal growth. There was no evidence of maternal harm prior to labour; adverse maternal effects occurred infrequently during labour. Maternal mammary gland development was normal.
Studies in knockout mice suggest absence of RANKL could interfere with maturation of the maternal mammary gland leading to impaired lactation post-partum.
Women who become pregnant during Denosumab (Prolia) treatment are encouraged to enrol in Amgen's Pregnancy Surveillance Program. Patients or their physicians should contact their local GSK representative to enrol.
Lactation: It is not known if Denosumab is excreted in human milk. Because Denosumab has the potential to cause adverse reactions in breast-feeding infants, a decision should be made whether to discontinue breast-feeding or discontinue the medicinal product.