Pregnancy: Risk Summary: Trastuzumab products can cause fetal harm when administered to a pregnant woman. In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Apprise the patient of the potential risks to a fetus. There are clinical considerations if a trastuzumab product is used in a pregnant woman or if a patient becomes pregnant within 7 months following the last dose of a trastuzumab product.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.
Clinical Considerations: Fetal/Neonatal Adverse Reactions: Monitor women who received Ogivri during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care.
Data: Human Data: In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting in the fetus as pulmonary hypoplasia, skeletal abnormalities and neonatal death. These case reports described oligohydramnios in pregnant women who received trastuzumab either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after trastuzumab was stopped. In one case, trastuzumab therapy resumed after amniotic index improved, and oligohydramnios recurred.
Animal Data: In studies where trastuzumab was administered to pregnant cynomolgus monkeys during the period of organogenesis at doses up to 25 mg/kg given twice weekly (up to 25 times the recommended weekly human dose of 2 mg/kg), trastuzumab crossed the placental barrier during the early (Gestation Days 20 to 50) and late (Gestation Days 120 to 150) phases of gestation. The resulting concentrations of trastuzumab in fetal serum and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but were not associated with adverse developmental effects.
Lactation: Risk Summary: There is no information regarding the presence of trastuzumab products in human milk, the effects on the breastfed infant, or the effects on milk production. Published data suggest human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts. Trastuzumab was present in the milk of lactating Cynomolgus monkeys but not associated with neonatal toxicity. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for Ogivri treatment and any potential adverse effects on the breastfed child from Ogivri or from the underlying maternal condition. This consideration should also take into account the trastuzumab product wash out period of 7 months [see Pharmacology: Pharmacodynamics under Actions].
Data: In lactating cynomolgus monkeys, trastuzumab was present in breast milk of about 0.3% of maternal serum concentrations after pre-(beginning Gestation Day 120) and post-partum (through Post-partum Day 28) doses of 25 mg/kg administered twice weekly (25 times the recommended weekly human dose of 2 mg/kg of trastuzumab products). Infant monkeys with detectable serum levels of trastuzumab did not exhibit any adverse effects on growth or development from birth to 1 month of age.
Females and Males of Reproductive Potential: Pregnancy Testing: Verify the pregnancy status of females of reproductive potential prior to the initiation of Ogivri.
Contraception: Females: Trastuzumab products can cause embryo-fetal harm when administered during pregnancy. Advise females of reproductive potential to use effective contraception during treatment with Ogivri and for 7 months following the last dose of Ogivri [see as previously mentioned and Pharmacology: Pharmacodynamics under Actions].