LEUKINE- sargramostim liquid
LEUKINE- sargramostim injection, powder, for solution
Genzyme Corporation
Rx only
DESCRIPTION
LEUKINE� (sargramostim) is a recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in a yeast (S. cerevisiae) expression system. GM-CSF is a hematopoietic growth factor which stimulates proliferation and differentiation of hematopoietic progenitor cells. LEUKINE is a glycoprotein of 127 amino acids characterized by three primary molecular species having molecular masses of 19,500, 16,800 and 15,500 daltons. The amino acid sequence of LEUKINE differs from the natural human GM-CSF by a substitution of leucine at position 23, and the carbohydrate moiety may be different from the native protein. Sargramostim has been selected as the proper name for yeast-derived rhu GM-CSF.
The liquid LEUKINE presentation is formulated as a sterile, preserved (1.1% benzyl alcohol), injectable solution (500 mcg/mL) in a vial. Lyophilized LEUKINE is a sterile, white, preservative-free powder (250 mcg) that requires reconstitution with 1 mL Sterile Water for Injection, USP or 1 mL Bacteriostatic Water for Injection, USP. Liquid LEUKINE has a pH range of 6.7 - 7.7 and lyophilized LEUKINE has a pH range of 7.1 - 7.7.
Liquid LEUKINE and reconstituted lyophilized LEUKINE are clear, colorless liquids suitable for subcutaneous injection (SC) or intravenous infusion (IV).
Liquid LEUKINE contains 500 mcg (2.8 x 106 IU/mL) sargramostim and 1.1% benzyl alcohol in a 1 mL solution. The vial of lyophilized LEUKINE contains 250 mcg (1.4 x 106 IU/vial) sargramostim.
The liquid LEUKINE vial and reconstituted lyophilized LEUKINE vial also contain 40 mg/mL mannitol, USP; 10 mg/mL sucrose, NF; and 1.2 mg/mL tromethamine, USP, as excipients. Biological potency is expressed in International Units (IU) as tested against the WHO First International Reference Standard. The specific activity of LEUKINE is approximately 5.6 x 106 IU/mg.
CLINICAL PHARMACOLOGY
General
GM-CSF belongs to a group of growth factors termed colony stimulating factors which support survival, clonal expansion, and differentiation of hematopoietic progenitor cells. GM-CSF induces partially committed progenitor cells to divide and differentiate in the granulocyte-macrophage pathways which include neutrophils, monocytes/macrophages and myeloid-derived dendritic cells.
GM-CSF is also capable of activating mature granulocytes and macrophages. GM-CSF is a multilineage factor and, in addition to dose-dependent effects on the myelomonocytic lineage, can promote the proliferation of megakaryocytic and erythroid progenitors.1 However, other factors are required to induce complete maturation in these two lineages. The various cellular responses (i.e., division, maturation, activation) are induced through GM-CSF binding to specific receptors expressed on the cell surface of target cells.2
