otic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but werenot associated with adverse developmental effects.
Hyaluronidase:
In an embryo-fetal study, mice have been dosed daily by subcutaneous injection during the period oforganogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is >7,200times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight andincreased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg,which is >1,200 times higher than the human dose.
In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, withhyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to1,100,000 U/kg, which is >3,600 times higher than the human dose. The study found no adverse effects onsexual maturation, learning and memory or fertility of the offspring.
8.2 Lactation
Risk Summary
There is no information regarding the presence of trastuzumab or hyaluronidase 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 the milk of lactating cynomolgus monkeys but not associated with neonatal toxicity(see Data). Consider the developmental and health benefits of breastfeeding along with the mother’s clinical needfor HERCEPTIN HYLECTA treatment and any potential adverse effects on the breastfed child fromHERCEPTIN HYLECTA or from the underlying maternal condition. This consideration should also take intoaccount the trastuzumab 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 of25 mg/kg administered twice weekly (25 times the recommended weekly human dose of 2 mg/kg of intravenous
trastuzumab). Infant monkeys with detectable serum levels of trastuzumab did not exhibit any adverse effects ongrowth 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 HERCEPTINHYLECTA.
Contraception
Females
HERCEPTIN HYLECTA can cause embryo-fetal harm when administered during pregnancy. Advise females ofreproductive potential to use effective contraception during treatment with HERCEPTIN HYLECTA and for 7months following the last dose of HERCEPTIN HYLECTA [see Use in Specific Populations (8.1) and ClinicalPharmacology (12.3)].
8.4 Pediatric Use
The safety and effectiveness of HERCEPTIN HYLECTA in pediatric patients have not been established.
8.5 Geriatric Use
Of the total number of patients in the HannaH and SafeHER studies treated with HERCEPTIN HYLECTA, 19%
were 65 and over, while 4.7% were 75 and over.
In patients receiving intravenous trastuzumab, the risk of cardiac dysfunction was increased in geriatric patientsas compared to younger patients, in both those receiving treatment for adjuvant therapy or metastatic disease.
Other differences in safety or effectiven |
