one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to the Zeva lin therapeutic regimen.
Cutaneous and mucocutaneous reactions: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, and exfoliative dermatitis [see Boxed Warning and Warnings and Precautions (5.3)].
Infusion site erythema and ulceration following extravasation [see Warnings and Precautions (5.7)].
Radiation injury in tissues near areas of lymphomatous involvement within a month of Zeva lin administration.
7 DRUG INTERACTIONS
No formal drug interaction studies have been performed with Zeva lin. Patients receiving medications that interfere with platelet function or coagulation should have more frequent laboratory monitoring for thrombocytopenia.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects: Category D [see Warnings and Precautions (5.6)]: Based on its radioactivity, Y-90 Zeva lin may cause fetal harm when administered to a pregnant woman. Immunoglobulins are known to cross the placenta. There are no adequate and well-controlled studies in pregnant women. Animal reproductive toxicology studies of Zeva lin have not been conducted.
Advise women of childbearing potential to use adequate contraception. Inform women who become pregnant while receiving Zeva lin of the potential fetal risks [see Patient Counseling Information (17)].
8.3 Nursing Mothers
Because human IgG is excreted in human milk, it is expected that Zeva lin would be present in human milk. Because of the potential for adverse reactions in nursing infants from Y-90 or In-111 Zeva lin, a decision should be made to discontinue nursing or not administer the Zeva lin therapeutic regimen, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and effectiveness of Zeva lin have not been established in pediatric patients.
8.5 Geriatric Use
Of 349 patients with relapsed/refractory NHL treated with the Zeva lin therapeutic regimen in clinical studies, 38% (132 patients) were age 65 years and over, while 12% (41 patients) were age 75 years and over.
Of 414 patients enrolled in Study 4 (Zeva lin following first-line chemotherapy) 206 patients received Zeva lin. Of these patients 14% (29 patients) were 65 years and over, while 2% (4 patients) were 75 years and older. In the control arm, 10% (21 patients) were 65 years or over and 0% (0 patients) were 75 years or older.
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.
10 OVERDOSAGE
Severe cytopenias which may require stem cell support have occurred at doses higher than the recommended maximum total dose of 32 mCi (1184 MBq).
11 DESCRIPTION
Zeva lin (ibritumomab tiuxetan) is the immunoconjugate resulting from a stable thiourea covalent bond between the monoclonal antibody ibritumomab and the linker-chelator tiuxetan [N-[2-bis(carboxymethyl)amino]-3-(p-isothiocyanatophenyl)-propyl]-[N-[2-bis(carboxymethyl)amino]-2-(methyl)-ethyl]glycine. This linker-chelator provides a high affinity, conformationally restricted chelation site for Indium-111 or Yttrium-90. The approximate molecular weight of ibritumomab tiuxetan is 148 kD. The antibody moiety of Zeva lin is ibritumomab, a mur |
