ic fever.
Bone Pain
The analysis of bone pain described below is based on a composite analysis using multiple, related, adverse event terms.
In the placebo-controlled study, the incidence of bone pain was 57% in Neulasta®-treated patients compared to 50% in placebo-treated patients. Bone pain was generally reported to be of mild-to-moderate severity.
Among patients experiencing bone pain, approximately 37% of Neulasta®- and 31% of placebo-treated patients utilized non-narcotic analgesics and 10% of Neulasta®- and 9% of placebo-treated patients utilized narcotic analgesics.
In the active-controlled studies, the use of non-narcotic and narcotic analgesics in association with bone pain was similar between Neulasta®- and Filgrastim-treated patients. No patient withdrew from study due to bone pain.
Laboratory Abnormalities
In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with non‑myeloid malignancies receiving Neulasta®. Leukocytosis was not associated with any adverse effects.
In the placebo-controlled study, reversible elevations in LDH, alkaline phosphatase, and uric acid that did not require treatment occurred at similar rates in Neulasta®- and placebo-treated patients.
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving Neulasta® has not been adequately determined. While available data suggest that a small proportion of patients developed binding antibodies to Filgrastim or pegfilgrastim, the nature and specificity of these antibodies has not been adequately studied. No neutralizing antibodies have been detected using a cell‑based bioassay in 46 patients who apparently developed binding antibodies. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Neulasta® with the incidence of antibodies to other products may be misleading.
Cytopenias resulting from an antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors. There is a theoretical possibility that an antibody directed against pegfilgrastim may cross‑react with endogenous G‑CSF, resulting in immune‑mediated neutropenia, but this has not been observed in clinical studies.
OVERDOSAGE
The maximum amount of Neulasta® that can be safely administered in single or multiple doses has not been determined. Single subcutaneous doses of 300 mcg/kg have been administered to 8 healthy volunteers and 3 patients with non‑small cell lung cancer without serious adverse effects. These patients experienced a mean maximum ANC of 55 x 109/L, with a corresponding mean maximum WBC of 67 x 109/L. The absolute maximum ANC observed was 96 x 109/L with a corresponding absolute maximum WBC observed of 120 x 109/L. The duration of leukocytosis ranged from 6 to 13 days. Leukapheresis should be considered in the management of symptomatic individuals.
DOSAGE AND ADMINISTRATION
The recommended dosage of Neulasta® is a single subcutaneous injection of 6 mg administered once per chemo |
