ed embryolethality and spontaneous abortions occurred at 4 times themaximum recommended human dose simultaneously with signs of maternal toxicity (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Allpregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population,the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4%and 15-20%, respectively.
Data
Animal Data
Pregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis.
At cumulative doses ranging from the approximate human dose to approximately 4 times the recommended humandose (based on body surface area), treated rabbits exhibited decreased maternal food consumption, maternal weightloss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural
anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses andspontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately 4 timesthe recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended
human dose.
Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10times the recommended human dose at the following stages of gestation: during the period of organogenesis, frommating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidenceof fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately 3and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers
(detected at the end of gestation but no longer present in pups eva luated at the end of lactation).
8.2 Lactation
Risk Summary
There are no data on the presence of pegfilgrastim products in human milk, the effects on the breastfed child, or theeffects on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim productsare not orally absorbed by neonates. The developmental and health benefits of breastfeeding should be consideredalong with the mother’s clinical need for UDENYCA and any potential adverse effects on the breastfed child fromUDENYCA or from the underlying maternal condition.
8.4 Pediatric Use
The safety and effectiveness of pegfilgrastim have been established in pediatric patients. No overall differences insafety were identified between adult and pediatric patients with pegfilgrastim based on postmarketing surveillanceand review of the scientific literature.
Use of pegfilgrastim in pediatric patients for chemotherapy-induced neutropenia is based on adequate and well
controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients with sarcoma [seeClinical Pharmacology (12.3) and Clinical Studies (14)].
8.5 Geriatric Use
Of the 932 patients with cancer who received pegfilgrastim in clinical studies, 139 (15%) were age 65 and over, and18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age65 and older and younger patients.
10 OVERDOSAGE
Overdosage of pegfilgrastim products may result in l |
