Hematologic Agent (Hematopoietic)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
No reports describing the use of peginesatide in human pregnancy have been located. Animal reproduction tests suggest risk, but the absence of human pregnancy experience prevents a more complete assessment of embryo–fetal risk.
FETAL RISK SUMMARY
Peginesatide is given as an IV or SC injection. It is a dimeric peptide that is covalently linked to a PEG chain. Peginesatide is indicated for the treatment of anemia due to chronic kidney disease in adult patients on dialysis. The agent binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red blood cell precursors. Peginesatide is not metabolized. The mean half-life in dialysis patients is 47.9 ± 17.7 hours (1).
Reproduction studies have been conducted in rats and rabbits. In rats given an IV every 3 days for a total of five doses, and every 5th day in rabbits for a total of three doses, adverse embryo–fetal effects included reduced fetal weights, increased resorption, embryo–fetal death, cleft palate (rats only), sternoschisis (rats only), variations in blood vessels (rats only), sternum anomalies, fused sternebrae (rabbits only), unossification of sternebrae and metatarsals, and reduced ossification of some bones. In rats, embryo–fetal toxicity was evident at doses of ≥1 mg/kg resulting in exposures (AUC) comparable to or higher than those in humans after IV administration at a dose of 0.35 mg/kg in patients on dialysis. In rabbits, adverse effects were observed at doses lower (5%–50%) than the dose of 0.35 mg/kg in patients (1).
Long-term carcinogenicity studies in rats were negative as were assays for mutagenic or clastogenic effects. In males and females given IV doses, peginesatide produced adverse effects in males including reduced weight of seminal vesicles and prostate. In females, decreased viable fetuses appeared to be due to preimplantation and postimplantation losses. There were no apparent drug-related effects on estrous cycles or the number of corpora lutea (1).
It is not known if peginesatide crosses the human placenta. The molecular weight (about 4900 for the dimeric peptide alone) suggests that the drug will not cross the placenta in spite of a relative long mean half-life. However, exposure during the 3rd trimester might still occur.
No reports describing the use of peginesatide during human lactation have been located. The molecular weight (about 4900 for the dimeric peptide alone) suggests that clinically significant amounts of the drug will not be excreted into breast milk in spite of a relative long (about 48 hours) mean half-life. Moreover, even if small amounts were excreted, they probably would be digested in the infant’s gut. Nonetheless, if the drug is used during lactation, the nursing infant should be monitored for the most common (≥10%) adverse effects in patients. These effects were dyspnea, diarrhea, nausea, and cough (1).
1.Product information. Omontys. Affymax, 2012.