OVERDOSAGE
In cancer patients receiving NEUPOGEN® as
an adjunct to myelosuppressive chemotherapy‚ it is recommended‚ to avoid the
potential risks of excessive leukocytosis‚ that NEUPOGEN®
therapy be discontinued if the ANC surpasses 10‚000/mm3
after the chemotherapy-induced ANC nadir has occurred. Doses of NEUPOGEN® that increase the ANC beyond 10‚000/mm3 may not result in any additional clinical benefit.
The maximum tolerated dose of NEUPOGEN® has not been
determined. Efficacy was demonstrated at doses of 4 to 8 mcg/kg/day in the phase
3 study of nonmyeloablative chemotherapy. Patients in the BMT studies received
up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of
the dose response curve above daily doses of greater than 10 mcg/kg/day.
In NEUPOGEN® clinical trials of cancer patients
receiving myelosuppressive chemotherapy‚ WBC counts > 100‚000/mm3 have been reported in less than 5% of patients‚ but were not
associated with any reported adverse clinical effects.
In cancer patients receiving myelosuppressive chemotherapy‚ discontinuation
of NEUPOGEN® therapy usually results in a 50% decrease in
circulating neutrophils within 1 to 2 days‚ with a return to pretreatment levels
in 1 to 7 days.
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REFERENCES
- Zsebo KM‚ Cohen AM‚ Murdock DC‚ et al. Recombinant human granulocyte
colony-stimulating factor: Molecular and biological characterization. Immunobiol. 1986;172:175-184.
- Welte K‚ Bonilla MA‚ Gillio AP‚ et al. Recombinant human G-CSF: Effects on
hematopoiesis in normal and cyclophosphamide treated primates. J Exp Med. 1987;165:941-948.
- Duhrsen U‚ Villeval JL‚ Boyd J‚ et al. Effects of recombinant human
granulocyte colony-stimulating factor on hematopoietic progenitor cells in
cancer patients. Blood. 1988;72:2074-2081.
- Souza LM‚ Boone TC‚ Gabrilove J‚ et al. Recombinant human granulocyte
colony-stimulating factor: Effects on normal and leukemic myeloid cells. Science. 1986;232:61-65.
- Weisbart RH‚ Kacena A‚ Schuh A‚ Golde DW. GM-CSF induces human neutrophil
IgA-mediated phagocytosis by an IgA Fc receptor activation mechanism. Nature. 1988;332:647-648.
- Kitagawa S‚ Yuo A‚ Souza LM‚ Saito M‚ Miura Y‚ Takaku F. Recombinant human
granulocyte colony-stimulating factor enhances superoxide release in human
granulocytes stimulated by chemotactic peptide. Biochem
Biophys Res Commun. 1987;1443:1146.
- Glaspy JA‚ Baldwin GC‚ Robertson PA‚ et al. Therapy for neutropenia in hairy
cell leukemia with recombinant human granulocyte colony-stimulating factor.
Ann Int Med. 1988;109:789-795.
- Yuo A‚ Kitagawa S‚ Ohsaka A‚ et al. Recombinant human granulocyte
colony-stimulating factor as an activator of human granulocytes: Potentiation of
responses triggered by receptor-mediated agonists and stimulation of C3bi
receptor expression and adherence. Blood.
1989;74:2144-2149.
- Gabrilove JL‚ Jakubowski A‚ Fain K‚ et al. Phase I study of granulocyte
colony-stimulating factor in patients with transitional cell carcinoma of the
urothelium. J Clin Invest. 1988;82:1454-1461.
- Morstyn G‚ Souza L‚ Keech J‚ et al. Effect of granulocyte colony-stimulating
factor on neutropenia induced by cytotoxic chemotherapy. Lancet. 1988;1:667-672.
- Bronchud MH‚ Scarffe JH‚ Thatcher N‚ et al. Phase I/II study of recombinant
human granulocyte colony-stimulating factor in patients receiving intensive
chemotherapy for small cell lung cancer. Br J Cancer.
1987;56:809-813.
- Gabrilove JL‚ Jakubowski A‚ Scher H‚ et al. Effect of granulocyte
colony-stimulating factor on neutropenia and associated morbidity due to
chemotherapy for transitional cell carcinoma of the urothelium. N Engl J Med. 1988;318:1414-1422.
- Neidhart J‚ Mangalik A‚ Kohler W‚ et al. Granulocyte colony-stimulating
factor stimulates recovery of granulocytes in patients receiving dose-intensive
chemotherapy without bone-marrow transplantation. J Clin
Oncol. 1989;7:1685-1691.
- Bronchud MH‚ Howell A‚ Crowther D‚ et al. The use of granulocyte
colony-stimulating factor to increase the intensity of treatment with
doxorubicin in patients with advanced breast and ovarian cancer. Br J Cancer. 1989;60:121-128.
- Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind,
placebo-controlled, phase III study of Filgrastim in remission induction and
consolidation therapy for adults with de novo Acute Myeloid Leukemia. Blood. 1997;90:4710-4718.
- Dale DC‚ Bonilla MA‚ Davis MW‚ et al. A
randomized controlled phase III trial of recombinant human granulocyte
colony-stimulating factor (Filgrastim) for treatment of severe chronic
neutropenia. Blood. 1993;81:2496-2502.
- Schroeder TM and Kurth R. Spontaneous chromosomal breakage and high
incidence of leukemia in inherited disease. Blood.
1971;37:96-112.
- Medlock ES, Kaplan DL, Cecchini M, Ulich TR, del Castillo J, Andresen J.
Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal
rat granulopoiesis. Blood. 1993;81:916-922.
- Calhoun DA, Rosa C, Christensen RD. Transplacental passage of recombinant
human granulocyte colony-stimulating factor in women with an imminent preterm
delivery. Am J Obstet Gynecol. 1996;174:1306-1311.
This product and its use are covered by the following US Patent
Nos.: 4,810,643; 4,999,291; 5,582,823; 5,580,755.
[AMGEN LOGO]
Manufactured by:
Amgen Manufacturing, Limited,
a subsidiary of Amgen Inc. One Amgen Center Drive Thousand Oaks,
California 91320-1799
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© 1991-2007 Amgen Inc. All rights reserved.
v.20.2 - Issue Date: 09/2007
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