The Prescribing Information provides guidance for use in specific populations in Section 8. The section begins with information on use during pregnancy, the potential risks to the unborn fetus, and relevant data from animal studies (PI Subsection 8.1). Subsections 8.2 and 8.3 in the Prescribing Information discuss lactation risks and risks to females and males of reproductive potential, respectively. The use of KADCYLA in the pediatric population and geriatric population is outlined in subsections 8.4 and 8.5, respectively. Subsection 8.6 covers use of KADCYLA in those with renal impairments. Subsection 8.7 notes the lack of data among those with hepatic impairment. Select the arrows in the slider for information on each of these populations.
8.1 Pregnancy
There is a pregnancy pharmacovigilance program for KADCYLA. If a patient becomes pregnant while taking KADCYLA or within 7 months of taking the last dose of KADCYLA, HCPs and patients should immediately report the exposure to Genentech.
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Risk Summary
KADCYLA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of KADCYLA in pregnant women. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death were observed in the postmarketing setting in patients treated with trastuzumab. Based on its mechanism of action, the DM1 component of KADCYLA can also cause embryo-fetal harm when administered to a pregnant woman. Patients should be warned about the potential risks to a fetus.
Fetal/Neonatal Adverse Reactions
Monitor women who received KADCYLA 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.
Human and Animal Data
Human Data
There are no available data on the use of KADCYLA in pregnant women. In the post-marketing setting, cases of oligohydramnios and of oligohydramnios sequence manifesting in the fetus as pulmonary hypoplasia, skeletal abnormalities, and neonatal death were observed in the postmarketing setting in patients treated with trastuzumab. These case reports describe 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 reoccurred.
Animal Data
There were no reproductive and developmental toxicology studies conducted with ado-trastuzumab emtansine. DM1 is toxic to rapidly dividing cells in animals and is genotoxic, suggesting it has the potential to cause embryotoxicity and teratogenicity. 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 (about 7 times the clinical dose), trastuzumab crossed the placental barrier during the early and late 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.
