Antineoplastic
PREGNANCY RECOMMENDATION: No Human Data—No Relevant Animal Data
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of ibritumomab tiuxetan in human pregnancy have been located. Rituximab has limited human pregnancy experience and immunosuppression has been the only documented developmental toxicity. However, the ibritumomab tiuxetan therapeutic regimen includes radioactive components. Because of this, ibritumomab tiuxetan should not be used in pregnancy. If inadvertent pregnancy does occur, the woman should be informed of the potential for embryo–fetal harm.
FETAL RISK SUMMARY
Ibritumomab tiuxetan is an immunoconjugate consisting of ibritumomab and the linker-chelator tiuxetan. Ibritumomab, a murine immunoglobulin G1 (IgG1) K monoclonal antibody, is directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Tiuxetan provides a high-affinity chelation site for indium-111 and yttrium-90. The therapeutic regimen includes indium-111 ibritumomab tiuxetan and yttrium-90 ibritumomab tiuxetan, prepared immediately before administration, and preceding rituximab (see also Rituximab). Ibritumomab tiuxetan, as part of the therapeutic regimen, is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma, including patients with rituximab refractory follicular non-Hodgkin’s lymphoma. In patients receiving the therapeutic regimen, the mean effective half-life for yttrium-90 activity in blood was 39 hours (1).
The ibritumomab tiuxetan therapeutic regimen may cause severe, infusion-related toxicity, including hypotension and other adverse effects. Premedication with acetaminophen and an antihistamine (e.g., diphenhydramine) is recommended before each infusion of rituximab (1). Hypotension in a pregnant woman could have deleterious effects on placental perfusion resulting in embryo and fetal harm.
Animal reproduction studies have not been conducted with ibritumomab tiuxetan. Neither have studies been conducted for carcinogenicity, mutagenicity, or effects on fertility. However, radiation is a potential carcinogen and mutagen. Moreover, the ibritumomab tiuxetan therapeutic regimen results in a significant radiation dose to the testes. The radiation dose to the ovaries has not been determined. Although it has not been studied, the therapeutic regimen does have the potential to cause toxic effects on the male and female gonads (1).
It is not known if ibritumomab tiuxetan of the components of the therapeutic regimen cross the human placenta. The high molecular weight (about 148,000) of ibritumomab tiuxetan suggests that it will not cross. However, human IG does cross and, therefore, ibritumomab tiuxetan, with the tightly bound radioactive components, may also cross. Rituximab, a component of the therapeutic regimen, does cross the placenta, at least at term (see Rituximab).
BREASTFEEDING SUMMARY
No reports describing the use of ibritumomab tiuxetan or its therapeutic regimen during human lactation have been located. The high molecular weight (about 148,000) of ibritumomab tiuxetan suggests that it will not be excreted into breast milk. It also is not known if rituximab, a component of the therapeutic regimen, is excreted into milk (see Rituximab). However, human IG is excreted into milk and, therefore, both rituximab and ibritumomab tiuxetan, with the tightly bound radioactive components, may also be excreted. The effects of this potential exposure on a nursing infant are unknown, but immunosuppression and other severe adverse effects, including those from radiation, are potential complications.
Reference
1.Product information. Zevalin. Biogen Idec, 2006.