ndoligohydramnios 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 humandose 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 andamniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but werenot 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 on thebreastfed infant, or the effects on milk production. Published data suggest human IgG is present in human milkbut does not enter the neonatal and infant circulation in substantial amounts. Trastuzumab was present in themilk of lactating cynomolgus monkeys but not associated with neonatal toxicity (see Data). Consider thedevelopmental and health benefits of breastfeeding along with the mother's clinical need for TRAZIMERAtreatment and any potential adverse effects on the breastfed child from TRAZIMERA or from the underlyingmaternal condition. This consideration should also take into account the trastuzumab product wash out period of7 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 of25 mg/kg administered twice weekly (25 times the recommended weekly human dose of 2 mg/kg oftrastuzumab products). Infant monkeys with detectable serum levels of trastuzumab did not exhibit any adverseeffects 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 TRAZIMERA.
Contraception
Females
Trastuzumab products can cause embryo-fetal harm when administered during pregnancy. Advise females ofreproductive potential to use effective contraception during treatment with TRAZIMERA and for 7 monthsfollowing the last dose of TRAZIMERA [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 patients as compared to younger patients in both those receiving treatment for metastatic disease inStudies 5 and 6, or adjuvant therapy in Studies 1 and 2. Limitations in data collection and differences in studydesign of the 4 studies of trastuzumab in adjuvant treatment of breast cancer preclude a determination ofwhether the toxicity profile of trastuzumab in older patients is different from younger patients.
The reportedclinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) oftrastuzumab treatment in older patients is different from that observed in patients <65 years of age formetastatic |
