tration of the BEXXAR therapeutic regimen. Emergency supplies including medications for the treatment of hypersensitivity reactions, e.g., epinephrine, antihistamines and corticosteroids, should be available for immediate use in the event of an allergic reaction during administration of the BEXXAR therapeutic regimen. Patients who have received murine proteins should be screened for human anti-mouse antibodies (HAMA). Patients who are positive for HAMA may be at increased risk of anaphylaxis and serious hypersensitivity reactions during administration of the BEXXAR therapeutic regimen.
Secondary Malignancies
Myelodysplastic syndrome (MDS) and/or acute leukemia were reported in 10% (24/230) of patients enrolled in the clinical studies and 3% (20/765) of patients included in expanded access programs, with median follow-up of 39 and 27 months, respectively. Among the 44 reported cases, the median time to development of MDS/leukemia was 31 months following treatment; however, the cumulative rate continues to increase.
Additional non-hematological malignancies were also reported in 54 of the 995 patients enrolled in clinical studies or included in the expanded access program. Approximately half of these were non-melanomatous skin cancers. The remainder, which occurred in 2 or more patients, included colorectal cancer (7), head and neck cancer (6), breast cancer (5), lung cancer (4), bladder cancer (4), melanoma (3), and gastric cancer (2). The relative risk of developing secondary malignancies in patients receiving the BEXXAR therapeutic regimen over the background rate in this population cannot be determined, due to the absence of controlled studies (see ADVERSE REACTIONS).
Pregnancy Category X
(see BOXED WARNINGS; CONTRAINDICATIONS).
Hypothyroidism
Administration of the BEXXAR therapeutic regimen may result in hypothyroidism (see ADVERSE REACTIONS, Hypothyroidism). Thyroid-blocking medications should be initiated at least 24 hours before receiving the dosimetric dose and continued until 14 days after the therapeutic dose (see DOSAGE and ADMINISTRATION). All patients must receive thyroid-blocking agents; any patient who is unable to tolerate thyroid-blocking agents should not receive the BEXXAR therapeutic regimen. Patients should be eva luated for signs and symptoms of hypothyroidism and screened for biochemical evidence of hypothyroidism annually.
PRECAUTIONS
Radionuclide Precautions
Iodine I 131 Tositumomab is radioactive. Care should be taken, consistent with the institutional radiation safety practices and applicable federal guidelines, to minimize exposure of medical personnel and other patients.
Renal Function
Iodine I 131 Tositumomab and Iodine-131 are excreted primarily by the kidneys. Impaired renal function may decrease the rate of excretion of the radiolabeled iodine and increase patient exposure to the radioactive component of the BEXXAR therapeutic regimen. There are no data regarding the safety of administration of the BEXXAR therapeutic regimen in patients with impaired renal function.
Immunization
The safety of immunization with live viral vaccines following administration of the BEXXAR therapeutic regimen has not been studied. The ability of patients who have received the BEXXAR therapeutic regimen to generate a primary or anamnestic humoral response to any vaccine has not been studied.
Information for Patients
