Immunologic Agent (Immunosuppressant)
PREGNANCY RECOMMENDATION: Compatible—Maternal Benefit >> Embryo–Fetal Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of basiliximab in human pregnancy have been located. The animal data suggest low risk, but the absence of human pregnancy experience prevents a full assessment of the embryo–fetal risk. A 2004 review concluded that immunosuppressive antibodies, such as basiliximab, have little implication for pregnancy because they are used either for induction immunosuppression or to prevent an acute rejection episode (1). If exposure does occur during pregnancy, the risk for developmental toxicity appears to be low, but long-term studies of exposed offspring for functional abnormalities and other developmental toxicity are warranted. The manufacturer recommends that women of childbearing potential use effective contraception before and during therapy, and for 4 months afterward (2).
FETAL RISK SUMMARY
Basiliximab, an interleukin-2 (IL-2) receptor antagonist, is a chimeric (murine/human) monoclonal antibody (IgG1k) indicated for the prophylaxis of acute organ rejection in patients receiving renal transplantation (2). Basiliximab is classified as a nondepleting (i.e., does not destroy T- or B-lymphocytes) protein immunosuppressant (3). It binds only to IL-2 receptor sites expressed on the surface of activated T-lymphocytes. This binding inhibits IL-2-mediated activation of lymphocytes. Basiliximab is used with immunosuppressive regimens that include cyclosporine and corticosteroids. The elimination half-life is about 7 days (2).
Reproduction studies have been conducted in monkeys. No maternal toxicity, embryotoxicity, or teratogenicity was observed when doses producing blood concentrations 13 times higher than those observed in humans were given during organogenesis. However, immunologic toxicity studies were not performed in the offspring (2).
It is not known if basiliximab crosses the human placenta. The molecular weight of the glycoprotein (about 144,000) may prevent transfer. However, the prolonged elimination half-life and the fact that immunoglobulin G molecules are known to cross the placenta, at least in the 3rd trimester, suggest that some exposure of the embryo and/or fetus will occur.
IL-2 receptors may have an important role in the development of the immune system, but the potential effect of basiliximab on this development was not evaluated in monkey offspring. Moreover, while in the circulation, basiliximab impairs the response of the immune system to antigenic challenges. It is unknown if the ability to respond to these challenges returns to normal after clearance of basiliximab (2).
BREASTFEEDING SUMMARY
No reports describing the use of basiliximab during human lactation have been located. Because immunoglobulins and other large molecules are excreted into colostrum in the first 2–3 days after birth, basiliximab is also probably excreted during this time. It may not be possible to avoid exposure during this early period of lactation because of the prolonged elimination half-life (about 7 days). Excretion into mature milk also is possible. Although partial digestion of the antibody in the gastrointestinal tract is probable, the effects, if any, on a nursing infant from this exposure are unknown.
References
1.Danesi R, Del Tacca M. Teratogenesis and immunosuppressive treatment. Transplant Proc 2004;36:705–7.
2.Product information. Simulect. Novartis Pharmaceuticals, 2005.
3.Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004;351:2715–29.