Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States

Entry and Attachment Inhibitors

Ibalizumab-uiyk (Trogarzo, IBA)

Summary

• Pharmacokinetic data are insufficient to make dosing recommendations for ibalizumab (IBA) during pregnancy.
• Clinical data are insufficient to characterize the risk for congenital anomalies associated with in utero exposure to IBA. No reproductive toxicity or teratogenicity concerns were identified in animal studies.
• Results from an enhanced pre- and postnatal development (ePPND) study conducted in cynomolgus monkeys suggest IBA may cause reversible immunosuppression in infants born to mothers exposed to this drug during pregnancy.

Human Studies in Pregnancy

Pharmacokinetics

No pharmacokinetic studies of IBA in pregnant women have been reported.

Placental and Breast Milk Passage

No data are available on placental or breast milk passage of IBA in humans. However, because monoclonal antibodies are transported across the placenta during pregnancy, IBA has the potential to be transmitted from the birthing parent to the developing fetus. Human immunoglobulin G also is present in human milk, although published data indicate that antibodies in breast milk do not enter the neonatal or infant circulation system in substantial amounts.¹

Teratogenicity/Adverse Pregnancy Outcomes

No data are available on the risk of birth defects in infants born to women who received IBA during pregnancy.

The Food and Drug Administration requires collection of prospective data in individuals exposed to IBA during pregnancy to monitor maternal and pregnancy outcomes, including adverse effects on the developing fetus, neonate, and infant.

Animal Studies

Carcinogenicity

Carcinogenicity and mutagenicity studies of IBA have not been conducted.¹

Reproduction/Fertility

Reproductive toxicology studies of IBA have not been conducted.¹

Teratogenicity/Adverse Pregnancy Outcomes

Results from an ePPND study conducted in cynomolgus monkeys suggest IBA may cause reversible immunosuppression in infants born to mothers exposed to this drug during pregnancy. Decreases in CD4 T lymphocyte (CD4) T cells and B cells and increases in CD8 T cells were observed within the first 4 weeks after birth in cynomolgus monkeys with in utero exposure; lymphocyte counts returned to near-normal levels by 3 months of age in these infant monkeys. No data are available for human infants with in utero exposure. However, based on these animal data, immune phenotyping of the peripheral blood, including CD4 lymphocyte T cell and B cell counts, is recommended for infants with in utero exposure to IBA. If immune suppression is observed, expert consultation also is recommended to provide guidance on monitoring and management (e.g., need for antibiotic or immunoprophylaxis) of exposed infants based on the degree of immunosuppression observed. The safety of administering live or live-attenuated vaccines in exposed infants who have significant immune suppression is unknown. Of note, no malformations or premature births were observed in the ePPND study.¹

Placental and Breast Milk Passage

No data are available on placental or breast milk passage of IBA in animals.

Excerpt from Table 14

Note: When using fixed-dose combination (FDC) tablets, refer to other sections in Appendix B and Table 14 in the Perinatal Guidelines for information about the dosing and safety of individual drug components of the FDC tablet during pregnancy.

References

1. Trogarzo (ibalizumab-uiyk) [package insert]. Food and Drug Administration. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761065s008lbl.pdf.