Antibivalirudin Antibodies

Bivalirudin is a relatively small polypeptide and thus is expected to lack significant antigenicity (Fenton et al., 1998). In a study of plasma samples from seven patients, no evidence for antibody formation (IgG, IgM, or IgE) was found (Fox et al., 1993) with plasma samples obtained at 7 and 14 days after iv administration. There was also no evidence for changes in the pharmacokinetics or pharma-codynamics of bivalirudin in their study. One patient exhibited antibody titers of greater than 1:2000 in the assay prior to administration of bivalirudin, although no explanation was given.

In another review of 494 bivalirudin-treated patients from nine different studies, 11 subjects initially tested positive for antibivalirudin antibodies (Berkowitz, 1999b). However, nine of these were found to be false positives on repeat testing. The remaining two (who could not be retested) did not develop any allergic or anaphylactic reactions. In clinical trials of bivalirudin performed from 1993 to 1995, only 1 of 3639 patients (0.03%) experienced an allergic reaction considered by the investigator to be related to study drug. In a study of 222 patients receiving bivalirudin subcutaneously two to three times daily for up to 14 days, no antibody formation occurred up to 6 wk (Ginsburg et al., 1994b; Eichler et al., 2004)

Since bivalirudin shares an 11-amino-acid sequence with hirudin, it is at least theoretically possible that patients with antilepirudin antibodies resulting from treatment with lepirudin could cross-react with bivalirudin. Eichler and colleagues

(2004) found that 22 of 43 (51%) sera containing antilepirudin antibodies showed reactivity in vitro against bivalirudin. This suggests that if bivalirudin is used in patients previously treated with lepirudin, extra caution should be used, e.g., careful anticoagulant monitoring, as antilepirudin antibodies sometimes influence pharmacokinetics.

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