with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No mutagenesis studies were conducted with pegfilgrastim. The carcinogenic potential of pegfilgrastim has not been eva luated in long‑term animal studies. In a toxicity study of 6 months duration in rats given once weekly subcutaneous injections of up to 1000 mcg/kg of pegfilgrastim (approximately 23‑fold higher than the recommended human dose), no precancerous or cancerous lesions were noted.
When administered once weekly via subcutaneous injections to male and female rats at doses up to 1000 mcg/kg prior to, and during mating, reproductive performance, fertility, and sperm assessment parameters were not affected.
Pregnancy Category C
Pegfilgrastim has been shown to have adverse effects in pregnant rabbits when administered subcutaneously every other day during gestation at doses as low as 50 mcg/kg/dose (approximately 4‑fold higher than the recommended human dose). Decreased maternal food consumption, accompanied by a decreased maternal body weight gain and decreased fetal body weights were observed at 50 to 1000 mcg/kg/dose. Pegfilgrastim doses of 200 and 250 mcg/kg/dose resulted in an increased incidence of abortions. Increased post‑implantation loss due to early resorptions was observed at doses of 200 to 1000 mcg/kg/dose, and decreased numbers of live rabbit fetuses were observed at pegfilgrastim doses of 200 to 1000 mcg/kg/dose, given every other day.
Subcutaneous injections of pegfilgrastim of up to 1000 mcg/kg/dose every other day during the period of organogenesis in rats were not associated with an embryotoxic or fetotoxic outcome. However, an increased incidence (compared to historical controls) of wavy ribs was observed in rat fetuses at 1000 mcg/kg/dose every other day. Very low levels (< 0.5%) of pegfilgrastim crossed the placenta when administered subcutaneously to pregnant rats every other day during gestation.
Once weekly subcutaneous injections of pegfilgrastim to female rats from day 6 of gestation through day 18 of lactation at doses up to 1000 mcg/kg/dose did not result in any adverse maternal effects. There were no deleterious effects on the growth and development of the offspring and no adverse effects were found upon assessment of fertility indices.
There are no adequate and well‑controlled studies in pregnant women. Neulasta® should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether pegfilgrastim is excreted in human milk. Because many drugs are excreted in human milk‚ caution should be exercised when Neulasta® is administered to a nursing woman.
Pediatric Use
The safety and effectiveness of Neulasta® in pediatric patients have not been established. The 6 mg fixed dose single‑use syringe formulation should not be used in infants, children, and smaller adolescents weighing less than 45 kg.
Geriatric Use
Of the 932 patients with cancer who received Neulasta® in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.
ADVERSE REACTIONS
See WARNINGS sections regarding Splenic Rupture, ARDS, Allergic Reactions, and Sickle Cell Disea |
