Indications and Usage
ZEVALIN® is a CD20-directed radiotherapeutic antibody administered
as part of the ZEVALIN therapeutic regimen indicated for the treatment of patients
- Relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL).
- Previously untreated follicular NHL who achieve a partial or complete response to
Important Safety Information
WARNING: SERIOUS INFUSION REACTIONS, PROLONGED AND SEVERE CYTOPENIAS, and SEVERE
AND MUCOCUTANEOUS REACTIONS
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. 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.
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.
Dosing: The dose of Y-90 ZEVALIN should not exceed 32.0 mCi (1184
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 diagnosis of MDS or AML was 1.9 years following treatment with
the ZEVALIN therapeutic regimen; however, the cumulative incidence continues to
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.
Extravasation: Monitor for extravasation and terminate infusion
if it occurs. Resume infusion in another limb.
Immunization: Do not administer live viral vaccines to patients
who recently received ZEVALIN.
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.
Embryo-fetal Toxicity: May cause fetal harm if given during pregnancy.
Impairment of Fertility: There is a potential risk that the ZEVALIN
therapeutic regimen could cause toxic effects on the male and female gonads. Effective
contraceptive methods should be used during treatment and for up to 12 months following
the ZEVALIN therapeutic regimen.
Nursing Mothers: Patients should be advised to discontinue nursing
during and after ZEVALIN treatment.
Adverse Reactions: The most common adverse reactions of ZEVALIN
are cytopenias, fatigue, nasopharyngitis, nausea, abdominal pain, asthenia, cough,
diarrhea, and pyrexia. Common adverse reactions (≥10%) in clinical trials were:
cytopenias, fatigue, nasopharyngitis, nausea, abdominal pain, asthenia, cough, diarrhea,
and pyrexia. The most serious adverse reactions of ZEVALIN are prolonged and severe
cytopenias (thrombocytopenia, anemia, lymphopenia, neutropenia) and secondary malignancies.
When administered following first-line chemotherapy, grade 3/4 adverse reactions
of ZEVALIN include prolonged and severe cytopenias (thrombocytopenia [51%], neutropenia
[41%], leukopenia [36%], lymphopenia [18%], and anemia [5%]) and secondary malignancies (12.7%).
Cytopenias were more severe and more prolonged among eleven (5%) patients who received
ZEVALIN after first-line fludarabine or a fludarabine-containing chemotherapy regimen
as compared to patients receiving non–fludarabine-containing regimens. Grade 3/4
infections occurred in 8% of ZEVALIN-treated patients and in 2% of controls and
included neutropenic sepsis (1%), bronchitis, catheter sepsis, diverticulitis, herpes
zoster, influenza, lower respiratory tract infection, sinusitis, and upper respiratory
Grade 3/4 adverse reactions of ZEVALIN in relapsed or refractory NHL patients include
prolonged and severe cytopenias (thrombocytopenia [63%], neutropenia [60%], anemia
[17%], and ecchymosis [<1%]) and secondary malignancies (5.2%). Serious infections
occurred in 3% of patients (urinary tract infection, febrile neutropenia, sepsis,
pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, and upper respiratory tract
infection). Life-threatening infections were reported in 2% of patients (sepsis,
empyema, pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis).
Please click here
to see the full Prescribing Information, including the BOXED WARNINGS, for ZEVALIN.
Because the ZEVALIN therapeutic regimen includes the use of rituximab, please also
consult Prescribing Information for rituximab