Antineoplastic
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of ipilimumab in human pregnancy have been located. Although the absence of human pregnancy experience prevents a better assessment of the risk, severe fetal toxicity was observed in pregnant monkeys. The drug should be considered contraindicated in pregnancy. However, melanoma is a potentially fatal disease. If a pregnant woman requires ipilimumab, she should be informed of the possible risk to her embryo and/or fetus.
FETAL RISK SUMMARY
Ipilimumab, an IgG1 kappa immunoglobulin, is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4). It is produced in mammalian (Chinese hamster ovary) cell culture. Ipilimumab is indicated for the treatment of unresectable or metastatic melanoma. Neither the metabolism nor plasma protein binding was reported by the manufacturer, but the terminal half-life was 14.7 days (1).
Cynomolgus monkeys were given IV ipilimumab every 21 days from the onset of organogenesis through parturition at doses that were 2.6 and 7.2 times the recommended human dose based on AUC. Severe toxicities including increased incidences of 3rd trimester abortion, stillbirth, premature delivery, low birth weight, and infant death were observed. In mice in which the gene for CTLA-4 had been deleted, offspring lacking CTLA-4 were born healthy, but died within 3–4 weeks due to multiorgan infiltration and damage by lymphocytes (1).
Studies evaluating carcinogenesis, mutagenesis, and impairment of fertility have not been conducted (1).
It is not known if ipilimumab crosses the human placenta. The molecular weight (about 148,000) suggests that it will not cross, at least early in pregnancy. However, human IgG1 is known to cross, and ipilimumab is an IgG1 (1). Moreover, the prolonged terminal half-life (14.5 days) will increase the opportunity for transfer. Thus, fetal exposure should be expected, especially in the latter part of pregnancy.
BREASTFEEDING SUMMARY
No reports describing the use of ipilimumab during human lactation have been located. The molecular weight (about 148,000) suggests that it will not be excreted into mature breast milk, However, human IgG1 is known to be excreted into colostrum, and ipilimumab is an IgG1 (1). Moreover, the prolonged terminal half-life (14.5 days) will increase the opportunity for excretion. The effect of this exposure on a nursing infant is unknown, but the best course is to not breastfeed if the mother requires ipilimumab.
Reference
1.Product information. Vervoy. Bristol-Myers Squibb, 2011.