Sargramostim (1 brand name, 1 dosage form, 0 routes)
Available dosage forms: VIAL.
Brand Names
- LEUKINE
Contraindications
Do not administer LEUKINE to patients with a history of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor such as sargramostim, yeast-derived products, or any component of the product. Anaphylactic reactions have been reported with LEUKINE [see Warnings and Precautions (5.1)].
Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1)] Infusion Related Reactions [see Warnings and Precautions (5.2)] Risk of Severe Myelosuppression when LEUKINE Administered within 24 Hours of Chemotherapy or Radiotherapy [see Warnings and Precautions (5.3)] Effusions and Capillary Leak Syndrome [see Warnings and Precautions (5.4)] Supraventricular Arrhythmias [see Warnings and Precautions (5.5)] Leukocytosis [see Warnings and Precautions (5.6)] Potential Effect on Malignant Cells [see Warnings and Precautions (5.7)] Immunogenicity [see Warnings and Precautions (5.8)] Risk of Serious Adverse Reactions in Infants Due to Benzyl Alcohol Preservative [see Warnings and Precautions (5.9)]
Mechanism of Action
Sargramostim (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. 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. The biological activity of GM-CSF is species-specific. Consequently, in vitro studies have been performed on human cells to characterize the pharmacological activity of GM-CSF. In vitro exposure of human bone marrow cells to GM-CSF at concentrations ranging from 1-100 ng/mL results in the proliferation of hematopoietic progenitors and in the formation of pure granulocyte, pure macrophage, and mixed granulocyte macrophage colonies. Chemotactic, anti-fungal, and anti-parasitic activities of granulocytes and monocytes are increased by exposure to GM-CSF in vitro. GM-CSF increases the cytotoxicity of monocytes toward certain neoplastic cell lines and activates polymorphonuclear neutrophils to inhibit the growth of tumor cells.
Overdosage
Doses up to 100 mcg/kg/day (4,000 mcg/m2/day or 16 times the recommended dose) were administered to four patients in a Phase 1 uncontrolled clinical study by continuous IV infusion for 7 to 18 days. Increases in WBC up to 200,000 cells/mm3 were observed. Adverse events reported were dyspnea, malaise, nausea, fever, rash, sinus tachycardia, headache, and chills. All these events were reversible after discontinuation of LEUKINE. In case of overdosage, discontinue LEUKINE therapy and monitor the patient for WBC increase and respiratory symptoms.