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Serious Allergic Reactions, Including Anaphylaxis
The BEXXAR therapeutic regimen can cause severe, including fatal, allergic reactions [see ADVERSE REACTIONS]. Premedicate with acetaminophen and diphenhydramine [see DOSAGE AND ADMINISTRATION]. Have medications for the treatment of allergic reactions available for immediate use during administration. Signs and symptoms of severe allergic reactions may include fever, rigors or chills, sweating, hypotension, dyspnea, bronchospasm, and nausea during or within 48 hours of infusion. Immediately interrupt BEXXAR infusions for severe reactions and provide appropriate medical and supportive care measures. Permanently, discontinue the BEXXAR therapeutic regimen in patients who develop serious allergic reactions.
Prolonged and Severe Cytopenias
Patients receiving the BEXXAR therapeutic regimen experienced severe (NCI CTC grade 3-4) and prolonged neutropenia (63%), thrombocytopenia (53%), and anemia (29%) [see ADVERSE REACTIONS]. The time to nadir was 4 to 7 weeks and the duration of cytopenias was approximately 30 days. Due to the variable nature of the onset of cytopenias, monitor patients with weekly complete blood counts for up to 12 weeks.
The BEXXAR therapeutic regimen should not be administered to patients with > 25% lymphoma marrow involvement, platelet count < 100,000 cells/mm³, or neutrophil count < 1,500 cells/mm³.
The BEXXAR therapeutic regimen contains Iodine-131. Follow institutional radiation safety practices and applicable federal guidelines to minimize radiation exposure during handling and after administration of the BEXXAR therapeutic regimen. Advise patients of the risks of radiation exposure of household contacts, pregnant women, and small children and of the steps to be taken to reduce these risks.
The BEXXAR therapeutic regimen should be administered only by physicians enrolled in the certification program for dose calculation and administration of the BEXXAR therapeutic regimen. Further information regarding the BEXXAR therapeutic regimen certification program is available by phone at 1-877-423-9927.
Myelodysplastic syndrome (MDS) or acute leukemia may occur with the use of the BEXXAR therapeutic regimen and were reported in 10% of patients enrolled in clinical trials and 3% of patients enrolled in the expanded access program (median follow-up of 39 and 27 months, respectively). The median time to development of MDS or leukemia was 31 months [see ADVERSE REACTIONS].
Non-hematologic malignancies may occur with the use of the BEXXAR therapeutic regimen and were reported in 5% of patients enrolled in clinical trials or the expanded access program. In the absence of controlled studies, the relative risk of secondary malignancies in patients receiving the BEXXAR therapeutic regimen cannot be determined [see ADVERSE REACTIONS].
The BEXXAR therapeutic regimen can cause hypothyroidism [see ADVERSE REACTIONS]. Initiate thyroid-blocking medications at least 24 hours before administering the dosimetric dose and continue until 14 days after the therapeutic dose [see DOSAGE AND ADMINISTRATION]. The risk of hypothyroidism is likely to be increased in patients who do not complete the recommended thyroid-protective regimen. Evaluate for clinical evidence of hypothyroidism and thyroid-stimulating hormone (TSH) level before treatment and annually thereafter.
The BEXXAR therapeutic regimen can cause fetal harm when administered to a pregnant woman including severe, and possibly irreversible, neonatal hypothyroidism. Inform patients who are pregnant or become pregnant after the BEXXAR therapeutic regimen about the potential hazard to a fetus. Evaluate infants born to mothers treated with the BEXXAR therapeutic regimen during pregnancy for hypothyroidism at time of delivery and during the neonatal period [see Use in Specific Populations].
Males and females of reproductive potential should use effective contraception during treatment with the BEXXAR therapeutic regimen and for 12 months after the therapeutic dose [see Use in Specific Populations].
Excessive Radiation Exposure in Patients With Impaired Renal Function
There are no data regarding the safety of administration of the BEXXAR therapeutic regimen in patients with impaired renal function. Since the BEXXAR therapeutic regimen is primarily cleared through the kidneys, the rate of excretion of radiolabeled iodine is expected to be decreased in patients with impaired renal function or obstructive uropathy, which may result in increased patient exposure to I-131 tositumomab. [See Use in Specific Populations, CLINICAL PHARMACOLOGY.]
The safety of immunization with live viral vaccines following administration of the BEXXAR therapeutic regimen and the ability of patients who have received the BEXXAR therapeutic regimen to generate a primary or anamnestic humoral response to any vaccine have not been studied. Do not administer live viral vaccines to patients recently treated with BEXXAR.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of the BEXXAR therapeutic regimen or to determine its effects on fertility in males or females. However, Iodine I-131 is a potential carcinogen and mutagen.
Administration of the BEXXAR therapeutic regimen exposes the testes and ovaries to radiation [see DOSAGE AND ADMINISTRATION].
Use In Specific Populations
Pregnancy: Category D [see WARNINGS AND PRECAUTIONS]: There are no studies of the BEXXAR therapeutic regimen in pregnant women or animals. Based on the transplacental passage of I-131, administration of the BEXXAR therapeutic regimen to a pregnant woman can cause fetal harm including severe and possibly irreversible neonatal hypothyroidism. Limited data suggest an increased risk of miscarriage up to a year following I-131 treatment.
Inform patients who are pregnant or become pregnant after the BEXXAR therapeutic regimen about the potential hazard to a fetus. Evaluate infants born to mothers treated with the BEXXAR therapeutic regimen for hypothyroidism at the time of delivery and during the neonatal period.
Because immunoglobulins are secreted in human milk, it is expected that tositumomab would be present in human milk. Radiolabeled iodine is excreted in breast milk and may reach concentrations equal to or greater than maternal plasma concentrations. Because of the potential for serious adverse reactions in nursing infants from the BEXXAR therapeutic regimen, advise women to discontinue nursing or to consider alternative treatment, taking into account the importance of the BEXXAR therapeutic regimen to the mother.
The safety and effectiveness of the BEXXAR therapeutic regimen have not been established in children.
Clinical studies of the BEXXAR therapeutic regimen did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects.
Use of the BEXXAR therapeutic regimen has not been studied in patients with renal impairment [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].
Females and Males of Reproductive Potential
Females of reproductive potential should use effective contraception during treatment with the BEXXAR therapeutic regimen and for 12 months after treatment ends to avoid the embryo-fetal effects of the radioisotope and the risk of increased pregnancy loss during that time period.
The BEXXAR therapeutic regimen exposes the testes to radiation [see DOSAGE AND ADMINISTRATION]. Because of the potential for mutagenesis in male gametes, males of reproductive potential should use effective contraception during treatment with the BEXXAR therapeutic regimen and for 12 months after treatment ends.
The BEXXAR therapeutic regimen results in radiation exposure of the ovaries and testes. Based on published studies examining patients treated with I-131, the BEXXAR therapeutic regimen may cause transient ovarian or testicular dysfunction. Radiation effects may persist for up to 12 months following treatment.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 9/27/2012
Additional Bexxar Information
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