Hematopoietic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of pegfilgrastim in human pregnancy have been located. Although the animal data do not suggest fetal risk, the absence of human pregnancy experience prevents an assessment of the embryo–fetal risk. Filgrastim has been used in the pregnancy without apparent fetal harm. (See Filgrastim.) Therefore, until human data are available, filgrastim would be preferred over pegfilgrastim in pregnancy.
FETAL RISK SUMMARY
Pegfilgrastim is a covalent conjugate of monomethoxypolyethylene glycol and filgrastim that results in reduced renal elimination and prolonged persistence in the serum. (See also Filgrastim.) Pegfilgrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia. The serum half-life depends on the dose and the number of neutrophils, ranging from 15 to 80 hours after SC injection (1).
Reproduction studies have been conducted in rats and rabbits. In rats, pegfilgrastim given SC in doses up to 1000 mcg/kg/dose every other day during organogenesis caused no embryotoxic or fetotoxic outcome. However, an increased incidence of wavy ribs was observed at the maximum dose. When doses up to 1000 mcg/kg/dose were given once weekly from gestation day 6 through lactation day 18, no maternal toxicity or adverse effects on the growth or development of offspring were observed. The highest dose was about 23 times the recommended human dose (RHD). In addition, the once-weekly dose in male and nonpregnant female rats had no effect on reproductive performance, fertility, or sperm parameters. In rabbits, SC doses as low as 4 times the RHD given every other day were maternally toxic (decreased food consumption and maternal weight gain) and fetotoxic (decreased body weights). At about 16 times the RHD or higher, there was an increased incidence of resorptions and abortions with a corresponding decrease in the number of live fetuses (1).
It is not known if pegfilgrastim crosses the human placenta, but filgrastim apparently reaches the fetus late in gestation in amounts sufficient to produce a biologic effect. (See Filgrastim.) The molecular weight of pegfilgrastim (about 39,000) is twice that of filgrastim (about 19,000) because of the polyethylene glycol. The addition of this nonamino acid moiety may prevent the transfer of pegfilgrastim in amounts sufficient to produce a biologic effect in the fetus.
BREASTFEEDING SUMMARY
No reports describing the use of pegfilgrastim during human lactation have been located. Pegfilgrastim is composed of monomethoxypolyethylene glycol and filgrastim that are chemically bound together. This produces a compound with a very long half-life (15–80 hours) and a very high molecular weight (about 39,000). Excretion into breast milk is doubtful, but even if the drug were excreted, it probably would be digested in a nursing infant’s stomach. The risk to a nursing infant is unknown but appears to be low to nonexistent. Therefore, treatment with pegfilgrastim should not be withheld because of breastfeeding.
Reference
1.Product information. Neulasta. Amgen, 2004.