Compound Name:OprelvekinMolecular Target:Interleukin-11 receptorMolecular Structure:recombinant, human IL-11Licensed Indication:risk of, or pre-existing, severe thrombocytopenia and/or need for platelet transfusions following myelosuppressive chemotherapy in patients with nonmyeloid malignanciesManufacturer and/or Distributor:WyethInitial FDA Approval:1997Summary:Oprelvekin (Neumega) is recombinant human interleukin-11 (IL-11). It is produced in E. coli, and it differs from the native molecule by the absence of the amino-terminal proline residue and the lack of glycosylation. These alterations do not change its bioactivity, either in vitro or in vivo. IL-11 can stimulate the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induce megakaryocyte maturation, all of which results in increased platelet production. IL-11 can also interact with multiple other cell types, including other hematopoietic lineages, epithelial cells, osteoclasts, neurons, and adipose tissue. It induces acute phase reactants and fever, and it can modulate extracellular matrix metabolism. These multipotent activities may be responsible for some of the adverse reactions to oprelvekin, and have suggested additional therapeutic applications. Oprevlekin is administered once daily be subcutaneous injections for courses of 10-21 days beginning after completion of chemotherapy. In 1997, oprevlekin was approved for maintenance of platelets levels in adult patients who have nonmyeloid malignancies and who are at high risk of severe thrombocytopenia following myelosuppressive chemotherapy. Significant serious safety concerns are: (1) allergic reactions, including anaphylaxis; (2) fluid retention, including peripheral edema, pulmonary edema, capillary leak syndrome, exacerbation of pre-existing effusions and congestive heart failure; dilutional anemia; (3) cardiac arrhythmias (mainly atrial fibrilliation/flutter); (4) stroke; (5) papilledema; and (6) periosteal bone formation (manifesting as bone pain)References

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