INTERACTIONS WITH OTHER MEDICINAL PRODUCTS1
In an interaction study, Prolia® did not affect the pharmacokinetics of midazolam, which is metabolized by cytochrome P450 3A4 (CYP3A4). This indicates that Prolia® should not alter the pharmacokinetics of medicinal products metabolized by CYP3A4.
There are no clinical data on the co-administration of denosumab and hormone replacement therapy (oestrogen), however the potential for a pharmacodynamic interaction is considered to be low.
In postmenopausal women with osteoporosis, the pharmacokinetics and pharmacodynamics of denosumab were not altered by previous alendronate therapy, based on data from a transition study (alendronate to denosumab).
There are no adequate data from the use of denosumab in pregnant women. Reproductive toxicity was shown in a study of cynomolgus monkeys, dosed throughout pregnancy with denosumab at AUC exposures 119-fold higher than the human dose.
Prolia® is not recommended for use in pregnant women and women of child-bearing potential not using contraception. Women should be advised not to become pregnant during and for at least 5 months after treatment with Prolia®.
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.
It is unknown whether denosumab is excreted in human milk. In genetically engineered mice in which RANKL has been turned off by gene deletion (a "knockout mouse"), studies suggest absence of RANKL (the target of denosumab) during pregnancy may interfere with maturation of the mammary gland leading to impaired lactation post-partum. A decision on whether to abstain from breastfeeding or to abstain from therapy with Prolia® should be made, taking into account the benefit of breastfeeding to the newborn/infant and the benefit of Prolia® therapy to the woman.
The complete Prolia®
Summary of Product Characteristics can be found here
RANKL: receptor activator of nuclear factor kappa-B ligand.
- Prolia® (denosumab) Summary of Product Characteristics. Amgen.