PRECAUTIONS
The ZEVALIN therapeutic regimen is intended as a single course treatment. The safety and toxicity profile from multiple courses of the ZEVALIN therapeutic regimen or of other forms of therapeutic irradiation preceding, following, or in combination with the ZEVALIN therapeutic regimen have not been established. Radionuclide Precautions: The contents of the ZEVALIN kit are not radioactive. However, during and after radiolabeling ZEVALIN with In-111 or Y-90, care should be taken to minimize radiation exposure to patients and to medical personnel, consistent with institutional good radiation safety practices and patient management procedures. Hypersensitivity: Anaphylactic and other hypersensitivity reactions have been reported following the intravenous administration of proteins to patients. 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 ZEVALIN. Patients who have received murine proteins should be screened for human anti-mouse antibodies (HAMA). Patients with evidence of HAMA have not been studied and may be at increased risk of allergic or serious hypersensitivity reactions during ZEVALIN therapeutic regimen administrations. Immunization: The safety of immunization with live viral vaccines following the ZEVALIN therapeutic regimen has not been studied. Also, the ability of patients who received the ZEVALIN therapeutic regimen to generate a primary or anamnestic humoral response to any vaccine has not been studied. Laboratory Monitoring: Complete blood counts (CBC) and platelet counts should be obtained weekly following the ZEVALIN therapeutic regimen and should continue until levels recover. CBC and platelet counts should be monitored more frequently in patients who develop severe cytopenia, or as clinically indicated. Drug Interactions: No formal drug interaction studies have been performed with ZEVALIN. Due to the frequent occurrence of severe and prolonged thrombocytopenia, the potential benefits of medications which interfere with platelet function and/or anticoagulation should be weighed against the potential increased risks of bleeding and hemorrhage. Patients receiving medications that interfere with platelet function or coagulation should have more frequent laboratory monitoring for thrombocytopenia. In addition, the transfusion practices for such patients may need to be modified given the increased risk of bleeding.
Carcinogenesis, Mutagenesis, Impairment of Fertility: No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of the ZEVALIN therapeutic regimen, or to determine its effects on fertility in males or females. However, radiation is a potential carcinogen and mutagen. The ZEVALIN therapeutic regimen results in a significant radiation dose to the testes. The radiation dose to the ovaries has not been established. There have been no studies to evaluate whether the ZEVALIN therapeutic regimen causes hypogonadism, premature menopause, azoospermia and/or mutagenic alterations to germ cells. 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.
Pregnancy Category D: SEE WARNINGS. Nursing Mothers: It is not known whether ZEVALIN is excreted in human milk. Because human IgG is excreted in human milk and the potential for ZEVALIN exposure in the infant is unknown, women should be advised to discontinue nursing and formula feeding should be substituted for breast feedings (see CLINICAL PHARMACOLOGY).
Geriatric Use: Of 349 patients treated with the ZEVALIN therapeutic regimen in clinical studies, 38% (132 patients) were age 65 years and over, while 12% (41 patients) were age 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Pediatric Use: The safety and effectiveness of the ZEVALIN therapeutic regimen in children have not been established.
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