appropriate for gestationalage and consistent with community standards of care.
Data
Human Data
In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios andof oligohydramnios sequence, manifesting in the fetus as pulmonary hypoplasia, skeletal abnormalities andneonatal death. These case reports described oligohydramnios in pregnant women who receivedtrastuzumab either alone or in combination with chemotherapy. In some case reports, amniotic fluid indexincreased after trastuzumab was stopped. In one case, trastuzumab therapy resumed after amniotic indeximproved, and oligohydramnios recurred.
Animal Data
In studies where trastuzumab was administered to pregnant cynomolgus monkeys during the period oforganogenesis at doses up to 25 mg/kg given twice weekly (up to 25 times the recommended weekly humandose of 2 mg/kg), trastuzumab crossed the placental barrier during the early (Gestation Days 20 to 50) andlate (Gestation Days 120 to 150) phases of gestation. The resulting concentrations of trastuzumab in fetalserum and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternalserum but were not associated with adverse developmental effects.
8.2 Lactation
Risk Summary
There is no information regarding the presence of trastuzumab products in human milk, the effects onthe breastfed infant, or the effects on milk production. Published data suggest human IgG is present inhuman 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 neonataltoxicity (see Data). Consider the developmental and health benefits of breastfeeding along with themother's clinical need for KANJINTI treatment and any potential adverse effects on the breastfed childfrom KANJINTI or from the underlying maternal condition. This consideration should also take intoaccount the trastuzumab product wash out period of 7 months [see Clinical Pharmacology (12.3)].
Data
In lactating cynomolgus monkeys, trastuzumab was present in breast milk at about 0.3% of maternal serumconcentrations 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/kgof trastuzumab products). Infant monkeys with detectable serum levels of trastuzumab did not exhibit anyadverse effects on growth or development from birth to 1 month of age.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to the initiation of KANJINTI.
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 KANJINTI and
for 7 months following the last dose of KANJINTI [see Use in Specific Populations (8.1) and Clinical
Pharmacology (12.3)].
8.4 Pediatric Use
The safety and effectiveness of trastuzumab products in pediatric patients have not been established.
8.5 Geriatric Use
Trastuzumab has been administered to 386 patients who were 65 years of age or over (253 in the adjuvanttreatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increasedin geriatric patien |
