Fatal Infusion Reaction; Cytopenias; Dosing; Cutaneous Reactions

Fatal Infusion Reactions

• Deaths have occurred within 24 hours of rituximab infusion, and essential component of the ibritumomab tiuxetan therapeutic regimen. These fatalities were associated with an infusion reaction symptom complex that included hypoxia, pulmonary inflitrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock.
• Approximately 80% of fatal infusion reactions occurred in association with the first rituximab infusion.
• Patients who develop severe infsion reactions should have rituximab, In-111 ibritumomab tiuxetan, and Y-90 ibritumomab tiuxetan infusions discontinued and receive medical treatment.

Prolonged and Severe Cytopenias

• Y-90 ibritumomab tiuxetan administration results in severe and prolonged cytopenias in most patients.
• This therapeutic regimen should not be administered to patients with greater than or equal to 25% lymphoma marrow involvement and/or impaired bone marrow reserve.

Dosing

• The prescribed, measured, and administered dose of Y-90 ibritumomab tiuxetan should not exceed the absolute maximum allowable dose of 32.0 mCi (1184 MBq).
• Y-90 ibritumomab tiuxetan should not be administered to patients with altered biodistribution as determined by imaging with In-111 ibritumomab tiuxetan.
• In-111 ibritumomab tiuxetan and Y-90 ibritumomab tiuxetan are radiopharmaceuticals and should be used only by physicians and other professionals qualified by training and experienced in the safe use and handling of radionuclides.

Severe Cutaneous and Mucocutaneous Reactions

• Severe cutaneous and mucocutaneous reactions, some with fatal outcome, have been reported in association with the ibritumomab tiuxetan (Zevalin) therapeutic regimen.
• Patients experiencing a severe cutaneous or mucocutaneous reaction should not receive any further component of the therapeutic regimen and should seek prompt medical evaluation (See WARNINGS and ADVERSE REACTIONS in package insert).