Darzalex SC Use In Pregnancy & Lactation

Pregnancy: Risk Summary: DARZALEX SC can cause fetal harm when administered to a pregnant woman. The assessment of associated risks with daratumumab products is based on the mechanism of action and data from target antigen CD38 knockout animal models (see Data as follows). There are no available data on the use of DARZALEX SC in pregnant women to evaluate drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
The combination of DARZALEX SC and lenalidomide, thalidomide or pomalidomide is contraindicated in pregnant women, because lenalidomide, thalidomide and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide or pomalidomide prescribing information on use during pregnancy.
Clinical Considerations: Fetal/Neonatal Adverse Reactions: Immunoglobulin G1 (IgG1) monoclonal antibodies are transferred across the placenta. Based on its mechanism of action, DARZALEX SC may cause depletion of fetal CD38 positive immune cells and decreased bone density. Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed.
Data: Animal Data: DARZALEX SC for subcutaneous injection contains daratumumab and hyaluronidase. Mice that were genetically modified to eliminate all CD38 expression (CD38 knockout mice) had reduced bone density at birth that recovered by 5 months of age. Data from studies using CD38 knockout animal models also suggest the involvement of CD38 in the regulation of humoral immune responses (mice), feto-maternal immune tolerance (mice), and early embryonic development (frogs).
No systemic exposure of hyaluronidase was detected in monkeys given 22,000 U/kg subcutaneously (12 times higher than the human dose) and there were no effects on embryo-fetal development in pregnant mice given 330,000 U/kg hyaluronidase subcutaneously daily during organogenesis, which is 45 times higher than the human dose.
There were no effects on pre- and post-natal development through sexual maturity in offspring of mice treated daily from implantation through lactation with 990,000 U/kg hyaluronidase subcutaneously, which is 134 times higher than the human doses.
Lactation: Risk Summary: There is no data on the presence of daratumumab and hyaluronidase in human milk, the effects on the breastfed child, or the effects on milk production. Maternal immunoglobulin G is known to be present in human milk. Published data suggest that antibodies in breastmilk do not enter the neonatal and infant circulations in substantial amounts. Because of the potential for serious adverse reactions in the breastfed child when DARZALEX SC is administered with lenalidomide, thalidomide or pomalidomide, advise women not to breastfeed during treatment with DARZALEX SC. Refer to lenalidomide, thalidomide or pomalidomide prescribing information for additional information.
Data: Animal Data: No systemic exposure of hyaluronidase was detected in monkeys given 22,000 U/kg subcutaneously (12 times higher than the human dose) and there were no effects on post-natal development through sexual maturity in offspring of mice treated daily during lactation with 990,000 U/kg hyaluronidase subcutaneously, which is 134 times higher than the human doses.
Females and Males of Reproductive Potential: DARZALEX SC can cause fetal harm when administered to a pregnant woman [see Pregnancy as previously mentioned].
Pregnancy Testing: With the combination of DARZALEX SC with lenalidomide, thalidomide or pomalidomide, refer to the lenalidomide, thalidomide or pomalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential.
Contraception: Advise females of reproductive potential to use effective contraception during treatment with DARZALEX SC and for 3 months after the last dose. Additionally, refer to the lenalidomide, thalidomide or pomalidomide labeling for additional recommendations for contraception.