Ibritumomab Tiuxetan (1 brand name, 1 dosage form, 1 route)
Available dosage forms: INJECTABLE.
Routes of administration: INJECTION.
Brand Names
- ZEVALIN
Boxed Warning
Serious Infusion Reactions: Deaths have occurred within 24 hours of rituximab infusion, an essential component of the Zevalin therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most (80%) fatalities occurred with the first rituximab infusion [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)]. Discontinue rituximab and Y-90 Zevalin infusions in patients who develop severe infusion reactions. Prolonged and Severe Cytopenias: Y-90 Zevalin administration results in severe and prolonged cytopenias in most patients. Do not administer Y-90 Zevalin to patients with ≥ 25% lymphoma marrow involvement and/or impaired bone marrow reserve [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)]. Severe Cutaneous and Mucocutaneous Reactions: Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the Zevalin therapeutic regimen. Discontinue rituximab and Y-90 Zevalin infusions in patients experiencing severe cutaneous or mucocutaneous reactions [see Warnings and Precautions (5.3) and Adverse Reactions (6.2)]. Dosing: The dose of Y-90 Zevalin should not exceed 32 mCi (1184 MBq) [see Dosage and Administration (2.2)].
Contraindications
None.
Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the label: Serious Infusion Reactions [see Boxed Warning andWarnings and Precautions (5.1)] . Prolonged and Severe Cytopenias [see Boxed Warning and Warnings and Precautions (5.2)]. Severe Cutaneous and Mucocutaneous Reactions [see Boxed Warning and Warnings and Precautions (5.3)]. Leukemia and Myelodysplastic Syndrome [see Warnings and Precautions (5.4)].
Drug Interactions
Patients receiving medications that interfere with platelet function or coagulation should have more frequent laboratory monitoring for thrombocytopenia. No formal drug interaction studies have been performed with Zevalin.
Mechanism of Action
Ibritumomab tiuxetan binds specifically to the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35). The apparent affinity (KD) of ibritumomab tiuxetan for the CD20 antigen ranges between approximately 14 to 18 nM. The CD20 antigen is expressed on pre-B and mature B lymphocytes and on > 90% of B-cell non-Hodgkin’s lymphomas (NHL). The CD20 antigen is not shed from the cell surface and does not internalize upon antibody binding. The chelate tiuxetan, which tightly binds Y-90, is covalently linked to ibritumomab. The beta emission from Y-90 induces cellular damage by the formation of free radicals in the target and neighboring cells. Ibritumomab tiuxetan binding was observed in vitro on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, and lymphoid follicles of the tonsil, as well as lymphoid nodules of other organs such as the large and small intestines.
Overdosage
Severe cytopenias which may require stem cell support have occurred at doses higher than the recommended maximum total dose of 32 mCi (1184 MBq).