Animal studies have failed to reveal evidence of malformations or premature births; however, reversible changes in immune cell levels were observed postnatally. Pregnant cynomolgus monkeys were administered 110 mg/kg IV doses every week from gestation day 20 to 22 (GD 20 to 22) until parturition on about GD 160. Relative to concurrent controls, significant changes in infant monkey immune cell levels were seen on postnatal day (PND) 14 (CD4+ T cells and B cells decreased [mean] 78% and 46%, respectively; CD8+ T cells increased 2.3-fold) and PND 28 (CD4+ T cells decreased [mean] 73%; CD8+ T cells increased 2.2-fold) which were attributed to in utero exposure to this drug; the lymphocyte changes correlated with infant drug serum levels and appeared to return to near normal levels between PND 28 and 91, when drug levels were almost undetectable. On PND 24, 1 treatment-group infant monkey died from a systemic viral infection with secondary superficial bacterial infection that was acquired postnatally; despite low incidence (1 of 20 infants), the death may be related to immunosuppression induced by this drug. On PND 14, this infant had decreased CD4+ T cells (93%) and B cells (92%), and decreased cellularity in the spleen, thymus, and mandibular lymph node; this infant had decreased CD8+ T cells (71%) on PND 14 (unlike the other infant monkeys exposed to this drug) and body weight decreased between PND 14 and 24. No structural abnormalities were seen in the infants exposed to this drug; no maternal toxicities (including no changes in maternal lymphocyte subsets or effects on embryofetal survival) were observed. There are no controlled data in human pregnancy.

To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry has been established; while this registry does not include this drug, it likely includes patients' concomitant antiretroviral agents. Health care providers are encouraged to prospectively register patients. For additional information: apregistry.com

IgG antibodies are transported across the placenta in increasing amounts as pregnancy progresses (largest amount during the third trimester). Administration of this drug during pregnancy may affect immune responses in infants exposed in utero. For infants with perinatal exposure to this drug, immune phenotyping of the peripheral blood (including CD4+ T cell and B cell counts) is recommended; expert consultation is also recommended to provide guidance regarding monitoring and management (e.g., need for antibiotic/immunoprophylaxis) of exposed infants based on degree of immunosuppression observed. The safety of administering live or live-attenuated vaccines in exposed infants is unknown.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

The manufacturer makes no recommendation regarding use during pregnancy.

US FDA pregnancy category: Not assigned.

Risk summary: Based on animal data, use of this drug during pregnancy may cause reversible immunosuppression (CD4+ T cell and B cell lymphocytopenia) in infants exposed to the drug in utero; no data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-A pregnancy exposure registry is available.
-Immunoglobulin G (IgG) antibodies (such as this drug) are transported across the placenta in significant amounts, especially near term; this drug may potentially be transferred from the mother to the developing fetus.
-Immune responses in infants exposed to this drug in utero may be affected; immune phenotyping of peripheral blood and expert consultation are recommended.
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk of reversible immunosuppression in infants exposed to this drug during pregnancy.

See references

Breastfeeding is not recommended during use of this drug.
-LactMed: Caution is recommended, especially while nursing newborn or preterm infants.

Excreted into human milk: Unknown
Excreted into animal milk: Data not available

Comments:
-No published data available on the use of this drug during breastfeeding; because this drug is a large protein molecule with a molecular weight of 150 kilodaltons, the amount in milk is like to be very low and absorption by the infant is unlikely as it is probably destroyed in the infant's gastrointestinal tract.
-Human immunoglobulin G (IgG) is present in human milk; published data indicate antibodies in breast milk do not enter neonatal or infant circulation system in substantial amounts.
-The effects in the nursing infant are unknown.
-The US CDC, American Academy of Pediatrics, and manufacturer advise HIV-infected women not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected.

This drug is a human IgG4 antibody. Holder pasteurization (62.5C for 30 minutes) reduces the level of endogenous IgG by up to 79%. In a study of 67 colostrum samples that underwent Holder pasteurization, IgG amounts decreased by 34% to 40%; specific IgG subclasses decreased by different amounts, with Holder pasteurization having little effect on IgG4 activity. None of the studies measured IgG activity.

See references