zevalin

Important safety information

Serious Infusion Reactions: Immediately discontinue rituximab and Y-90 Zevalin. ( 5.1 , 6.1 ) Prolonged and Severe Cytopenias: Do not administer Zevalin to patients with ≥ 25% lymphoma marrow involvement or impaired bone marrow reserve. ( 5.2 , 6.1 ) Severe Cutaneous and Mucocutaneous Reactions: Discontinue rituximab and Zevalin infusions if patients develop severe cutaneous or mucocutaneous reactions. ( 5.3 , 6.2 ) Development of Leukemia and Myelodysplastic Syndrome: Monitor patients for hematological toxicity including secondary malignancies. ( 5.4 , 6.1 ) Extravasation: Monitor for extravasation and terminate infusion if it occurs. Resume infusion in another limb. ( 5.5 , 6.2 ) Immunization: Do not administer live viral vaccines to patients who recently received Zevalin. ( 5.6 ) Embryo-fetal Toxicity: May cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.8 , 8.1 , 8.3 ) 5.1 Serious Infusion Reactions Rituximab, alone or as a component of the Zevalin therapeutic regimen, can cause severe, including fatal, infusion reactions. These reactions typically occur during the first rituximab infusion with time to onset of 30 to 120 minutes. Signs and symptoms of severe infusion reactions may include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, and cardiogenic shock. Temporarily slow or interrupt the rituximab infusion for less severe infusion reactions. Immediately discontinue rituximab and Y-90 Zevalin administration for severe infusion reactions. Only administer rituximab/Zevalin in facilities where immediate access to resuscitative measures is available [ see Boxed Warning and Dosage and Administration ( 2.2 ) ]. See also prescribing information for rituximab. 5.2 Prolonged and Severe Cytopenias Cytopenias with delayed onset and prolonged duration, some complicated by hemorrhage and severe infection, are the most common severe adverse reactions of the Zevalin therapeutic regimen. When used according to recommended doses, the incidences of severe thrombocytopenia and neutropenia are greater in patients with mild baseline thrombocytopenia (≥ 100,000 but ≤ 149,000/mm 3 ) compared to those with normal pretreatment platelet counts. Severe cytopenias persisting more than 12 weeks following administration can occur. Monitor complete blood counts (CBC) and platelet counts following the Zevalin therapeutic regimen weekly until levels recover or as clinically indicated [ see Boxed Warning and Adverse Reactions ( 6.1 ) ]. Do not administer the Zevalin therapeutic regimen to patients with ≥ 25% lymphoma marrow involvement and/or impaired bone marrow reserve. Monitor patients for cytopenias and their complications (e.g., febrile neutropenia, hemorrhage) for up to 3 months after use of the Zevalin therapeutic regimen. Avoid using drugs which interfere with platelet function or coagulation following the Zevalin therapeutic regimen. 5.3 Severe Cutaneous and Mucocutaneous Reactions Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, and exfoliative dermatitis, some fatal, were reported in post-marketing experience. The time to onset of these reactions was variable, ranging from a few days to 4 months after administration of the Zevalin therapeutic regimen. Discontinue the Zevalin therapeutic regimen in patients experiencing a severe cutaneous or mucocutaneous reaction [ see Boxed Warning and Adverse Reactions ( 6.2 ) ]. 5.4 Risk of Developing Myelodysplastic Syndrome, Leukemia, and Other Malignancies The radiation dose resulting from therapeutic exposure to Y-90 radiolabeled Zevalin may result in secondary malignancies. Myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML) were reported in 5.2% (11/211) of patients with relapsed or refractory NHL enrolled in clinical studies and 1.5% (8/535) of patients included in the expanded-access trial, with median follow-up of 6.5 and 4.4 years, respectively. Among the 19 reported cases, the median time to the diagnosis of MDS or AML was 1.9 years following treatment with the Zevalin therapeutic regimen; however, the cumulative incidence continues to increase [ see Adverse Reactions ( 6.1 ) ]. Among 204 patients receiving Y-90 Zevalin following first-line chemotherapy, 26 (12.7%) patients in the Zevalin arm developed a second primary malignancy compared to 14 (6.8%) of patients in the control arm. Seven patients (3.4%, 7/204) were diagnosed with MDS/AML after receiving Zevalin, compared to one patient (0.5%, 1/205) in the control arm, with a median follow-up of 7.3 years. Deaths due to second primary malignancy included 8 (3.9%) patients in the Zevalin arm compared to 3 (1.5%) patients in the control arm. Deaths due to MDS/AML included five (2.5%) patients in the Zevalin arm compared to no patients in the control arm. Monitor patients for hematological toxicity including development of MDS or AML. 5.5 Extravasation Monitor patients closely for evidence of extravasation during Zevalin infusion. Immediately terminate the infusion if signs or symptoms of extravasation occur and restart in another limb [ see Dosage and Administration ( 2.2 ) ] . 5.6 Risks of Immunization The safety of immunization with live viral vaccines following the Zevalin therapeutic regimen has not been studied. Do not administer live viral vaccines to patients who have recently received Zevalin. The ability to generate an immune response to any vaccine following the Zevalin therapeutic regimen has not been studied. 5.7 Radionuclide Precautions During and after radiolabeling Zevalin with Y-90, minimize radiation exposure to patients and to medical personnel, consistent with institutional good radiation safety practices and patient management procedures. 5.8 Embryo-Fetal Toxicity Based on its radioactivity, Y-90 Zevalin may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for a minimum of twelve months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.1 )] .