Compound Name:RituximabMolecular Target:CD20Molecular Structure:chimeric IgG1?, recombinantLicensed Indication:rheumatoid arthritis; B-cell non-Hodgkin's lymphomaManufacturer and/or Distributor:Genentech; Biogen IdecInitial FDA Approval:2011Summary:Rituximab (Rituxan) is a chimeric (murine/human) IgG1k monoclonal antibody directed against the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35), a hydrophobic transmembrane protein located on pre-B and mature B lymphocytes, as well as on greater than 90% of B-cell non-Hodgkin’s lymphomas (NHL). CD20 is not, however, found on hematopoietic stem cells, pro-B-cells, normal plasma cells or other normal tissues. The function of the CD20 is not clear, although it may play a role in calcium ion flux. Rituximab is cytotoxic to CD20+ cells. Its mechanism of action in vivo probably includes complement-mediated lysis, ADCC (antibody mediated cellular cytotoxicity), and direct cell killing by apoptosis. It is administered by a course of two to four intravenous infusions over two to four weeks, which may be repeated at intervals of six months or more. Rituximab is administered by iv infusion. In 1997, rituximab was licensed as the first monoclonal antibody for the treatment of malignancies. The initial indication was for relapsed or refractory low grade or follicular B-cell non-Hodgkin lymphoma. In 2006, it was approved to be a first line agent for follicular CD20 positive B cell NHL in combination with CVP chemotherapy. In 2010, an indication was added for CD20 positive chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide for both previously treated and untreated patients. In 2014, rituximab together with idelalisib was approved for the treatment of patients with relapsed CLL. Rituximab is now widely used in the treatment of follicular and diffuse large B-cell NHL. Beginning soon after rituximab’s initial approval, it was tested in a wide variety of autoimmune diseases. In 2006, it was approved for use in combination with methotrexate for the treatment of anti-TNF refractory rheumatoid arthritis. In 2011, Wegener’s Granulomatosis and Microscopic Polyangiitis (ANCA positive vasculitis) were also added as an approved indication. Serious adverse reactions associated with rituximab include fatal infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, progressive multifocal leukoencephalopathy, reactivation of hepatitis B, cytopenias, infections, cardiac arrhythmias and bowel obstruction.References

Package Insert: http://www.gene.com/gene/products/information/pdf/rituxan-prescribing.pdf

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