This drug should not be used during pregnancy or in patients of childbearing potential not using effective contraception unless the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned.

Risk summary: Based on animal data and its mechanism of action, this drug can cause fetal harm; insufficient human data available for exposure of this drug in pregnant women.

Comments:
-Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; because this drug is an IgG1, it may be transmitted from the mother to the developing fetus.
-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 harm to the fetus.
---Pregnancies should be reported to Bristol-Myers Squibb at 1-844-593-7869.
-Pregnancy status in patients of childbearing potential should be verified before starting this drug.
-Patients of childbearing potential should be advised to use effective contraception during therapy and for 3 months after the last dose; local protocol should be consulted regarding contraception timing.

Animal studies have revealed evidence of embryolethality and teratogenicity. Pregnant cynomolgus monkeys received this drug every 3 weeks from onset of organogenesis through parturition. While no therapy-related adverse effects on reproduction were detected during the first 2 trimesters, starting in the third trimester, exposures about 2.6 to 7.2 times the human exposure at 3 mg/kg resulted in dose-related increases in abortion, stillbirth, premature delivery (with corresponding lower birth weight), and increased incidence of infant mortality. Additionally, developmental abnormalities were observed in the urogenital system of 2 infant monkeys exposed in utero to 30 mg/kg (7.2 times the human exposure based on AUC at 3 mg/kg); a female infant monkey had unilateral renal agenesis of the left kidney and ureter, and a male infant monkey had an imperforate urethra with associated urinary obstruction and subcutaneous scrotal edema. There are no controlled data in human pregnancy.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

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.

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The amount of this drug in breast milk appears to be very low but may increase with subsequent doses during a treatment cycle. Since this drug is a large protein molecule (molecular weight of 148 kilodaltons), it is also likely to be partially destroyed in the infant's gastrointestinal tract; absorption by the infant is probably minimal.

Soon after delivery, a woman with recurrent malignant melanoma received 3 mg/kg IV (over 90 minutes) every 3 weeks for 4 doses. Breast milk and serum samples were collected before she began therapy and at various times over the first 2 dosage intervals; 26 daily breast milk samples were obtained. Breast milk drug levels were highest (about 90 mcg/L) at 10 days after the first infusion and were lowest (41 mcg/L) at the time of the second infusion, 19 days after the first infusion. A peak milk level of 147 mcg/L was reached 4 days after the second infusion; it was apparent that accumulation occurred after the second dose. According to author estimation, a fully breastfed infant would receive a total of 4.5 mg of this drug over a 4-month treatment cycle.

Until more data become available, caution is recommended, particularly while breastfeeding newborn or preterm infants.
-According to some authorities: Breastfeeding is not recommended during use of this drug and for 3 months after the last dose.
-According to some authorities: A decision should be made to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother and the benefit of breastfeeding for the child.

Excreted into human milk: Yes (low amounts)

Comments:
-Secretion of immunoglobulin G (IgG) in human milk is generally limited and IgG has a low oral bioavailability; significant systemic exposure of the infant is not expected.
-The effects in the nursing infant are unknown; there is the potential for serious adverse reactions.

See references