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Rasburicase
General information
Rasburicase is recombinant urate oxidase, which causes the breakdown of uric acid to 5-hydroxyisourate, which is further broken down to allantoin. Although there is a gene for urate oxidase in human, it is non-functional, and purine catabolism therefore ends with uric acid. This may be advantageous, because uric acid is an antioxidant. In the root nodules of legumes urate oxidase is necessary for nitrogen fixation.
Rasburicase is used in the prevention and treatment of chemotherapy-induced hyperuricemia in patients with hematological malignancies [ ]. In early clinical trials in patients who had received cancer chemotherapy rasburicase significantly reduced plasma uric acid concentrations from baseline by 2–4 times more than oral allopurinol 10 mg/kg/day. In these trials there was no evidence of renal impairment; rashes occurred in about 2% of patients, and bronchospasm, nausea and vomiting, and hemolysis less often.
Rasburicase has also been used to treat acute gout in a patient who developed severe urticaria/angioedema after receiving allopurinol, did not tolerate colchicine, and responded poorly to other treatments [ ].
Drug studies
Observational studies
In 173 children and 72 adults with malignancy who were treated with intravenous rasburicase 0.20 mg/kg/day for 1–7 days there was a dramatic reduction in uric acid concentrations in all patients whether they received it for prophylaxis (n = 79) or treatment (n = 166) [ ]. The median post-treatment concentrations were 30–42 μmol/l. Repeated administrations were also effective in 11 patients. Four children and five adults had mild adverse reactions that were drug related or of unknown cause; in two children, the adverse events occurred during the second course.
In eight patients who received rasburicase, a single dose produced rapid sustained reduction of plasma uric acid concentrations, and the effect was sustained for up to 96 hours; no adverse events were reported [ ].
In a prospective study in 37 Korean children with hematological malignancies intravenous rasburicase 0.2 mg/kg/day was given for 3–5 days [ ]. Drug-related adverse effects were mild and reversible and there were no grade 4 or serious adverse events.
Rasburicase was ineffective in controlling tumor lysis syndrome in a 4-day-old neonate with congenital precursor B cell acute lymphoblastic leukemia, despite several intravenous doses (two doses of 0.1 mg/kg and four doses of 0.2 mg/kg) and aggressive supportive therapy [ ]. The authors suggested that in the presence of immature renal function other interventions and alternative antitumor strategies may be needed.
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