Anaphylaxis Associated with Administration of Repeated Courses of Rasburicase: A Research On Adverse Drug Events and Reports (RADAR) Project

Rasburicase (recombinant urate oxidase) is used to rapidly metabolize uric acid in patients with hyperuricemia. Rasburicase is considered immunogenic given that it is produced by a genetically modified Saccharomyces cerevisiae. Rasburicase labeling indicates that anaphylaxis rarely occurs (<1% of patients) after a single course of therapy, yet has been shown to elicit an antibody response in 64% of healthy volunteers within one to six weeks after the initial course, and with persistent antibodies for well over one year. Currently there are no data available on the incidence of anaphylaxis in patients receiving a subsequent rasburicase course after an interval of at least three weeks. We sought to determine the incidence of anaphylaxis after repeated courses of rasburicase during subsequent episodes of hyperuricemia.

Electronic medical records were used to identify patients with hematological malignancies who were treated with rasburicase for separate episodes of hyperuricemia. All evaluable patients received subsequent identical low doses of rasburicase (3mg or 6mg) for separate hyperuricemia episodes with at least 21 day intervals. Anaphylaxis included diagnostic coding and documentation in the record of angioedema and airway compromise.

Ninety-seven patients met criteria for inclusion in the study. No patients experienced anaphylaxis during the first treatment course of rasburicase, however six patients (6.2%) experienced anaphylaxis after a subsequent course (p=0.03), three of which required intubation, and two resulted in cardiac arrest with one death (see Table 1). The subsequent course of rasburicase associated with anaphylaxis was administered an average of 8.5 months after the first course and anaphylaxis occurred, on average, 93 minutes after rasburicase was administered. Notably, two of the six patients met laboratory criteria for tumor lysis syndrome at the time of the anaphylactic reaction. There was no evidence of hemolysis in the six patients, and they were not tested for G6PD deficiency or methemoglobinemia. The calculated number needed to harm after administration of a subsequent course of rasburicase is 17 (95% CI 9.1 – 71.9).

This study indicates that, in our population, the incidence of anaphylaxis after the administration of subsequent treatment courses of rasburicase for hyperuricemic episodes may be greater than that described in the FDA-approved package insert for initial treatment courses. Caution is advised given the serious nature of the events (i.e. anaphylaxis, cardiac arrest, death) when administering repeated courses of rasburicase, and as with other agents that may predispose to immediate hypersensitivity reactions, premedication with antihistamines and corticosteroids should be considered.

Off Label Use: Rasburicase is not approved for the administration of repeated courses of therapy.