Overview
11 DESCRIPTION Rituximab-abbs is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituximab-abbs has an approximate molecular weight of 145 kD. Rituximab-abbs is produced by mammalian cell (Chinese Hamster Ovary) suspension culture in a nutrient medium.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Rituximab-abbs is a monoclonal antibody. Rituximab products target the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab products mediate B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In this setting, B cells may be acting at multiple sites in the autoimmune/inflammatory process, including through production of rheumatoid factor (RF) and other autoantibodies, antigen presentation, T-cell activation, and/or proinflammatory cytokine production. 12.
Indications
- 1 INDICATIONS AND USAGE TRUXIMA (rituximab-abbs) is a CD20-directed cytolytic antibody indicated for the treatment of adult patients with: Non-Hodgkin's Lymphoma (NHL) ( 1.1 ). Relapsed or refractory, low grade or follicular, CD20-positive B-cell NHL as a single agent. Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy.
Common Doses
- 375 mg
- 500 mg
- 250 mg
- 1000 mg
Dosage
2 DOSAGE AND ADMINISTRATION Administer only as an intravenous infusion ( 2.1 ). Do not administer as an intravenous push or bolus ( 2.1 ). TRUXIMA should only be administered by a healthcare professional with appropriate medical support to manage severe infusion-related reactions that can be fatal if they occur( 2.1 ). The dose for NHL is 375 mg/m 2 ( 2.2 ). The dose for CLL is 375 mg/m 2 in the first cycle and 500 mg/m 2 in cycles 2-6, in combination with FC, administered every 28 days ( 2.3 ). The dose as a component of Zevalin ® (ibritumomab tiuxetan) Therapeutic Regimen is 250 mg/m 2 ( 2.
Black Box Warning
WARNING: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) WARNING: FATAL INFUSION-RELATED REACTIONS, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY See full prescribing information for complete boxed warning. Fatal infusion-related reactions within 24 hours of rituximab infusion; approximately 80% of fatal reactions occurred with first infusion. Monitor patients and discontinue TRUXIMA infusion for severe reactions ( 5.1 ).
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Infusion-related reactions [ see Warnings and Precautions (5.1) ] Severe mucocutaneous reactions [ see Warnings and Precautions (5.2) ] Hepatitis B reactivation with fulminant hepatitis [ see Warnings and Precautions (5.3) ] Progressive multifocal leukoencephalopathy [ see Warnings and Precautions (5.4) ] Tumor lysis syndrome [ see Warnings and Precautions (5.5) ] Infections [ see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Formal drug interaction studies have not been performed with rituximab products. In patients with CLL, rituximab did not alter systemic exposure to fludarabine or cyclophosphamide. In clinical trials of patients with RA, concomitant administration of methotrexate or cyclophosphamide did not alter the pharmacokinetics of rituximab. Renal toxicity when used in combination with cisplatin ( 5.8 ).