Rasburicase response

Hemolysis

Rasburicase is contraindicated in patients with G6PD deficiency because hydrogen peroxide is one of the major by-products of the conversion of uric acid to allantoin. In clinical studies, hemolysis occurs in <1% patients receiving rasburicase; severe hemolytic reactions occurred within 2–4 days of the start of rasburicase. Immediately and permanently discontinue rasburicase administration in any patient developing hemolysis. Institute appropriate patient monitoring and support measures (e.g., transfusion support). Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting rasburicase.

Methemoglobinemia

In clinical studies, methemoglobinemia occurred in <1% patients receiving rasburicase. These included cases of serious hypoxemia requiring intervention with medical support measures. It is not known whether patients with deficiency of cytochrome b5 reductase (formerly known as methemoglobin reductase) or of other enzymes with antioxidant activity are at increased risk for methemoglobinemia or hemolytic anemia. Immediately and permanently discontinue rasburicase administration in any patient identified as having developed methemoglobinemia. Institute appropriate monitoring and support measures (e.g., transfusion support, methylene-blue administration).

Please review the complete therapeutic recommendations that are located here: (1).

[…]

As stated above, rasburicase use is contraindicated by the FDA, the European Medicines Agency, and the Pharmaceuticals and Medical Devices Agency in those with G6PD deficiency. If, on the basis of genotyping, a deficient status can be unambiguously assigned to a patient, that would be a sufficient contraindication to the use of rasburicase. However, due to the limitations of genetic testing (discussed above), in most cases it is necessary to perform G6PD enzyme testing to assign G6PD status.

The FDA recommends that patients at higher risk of G6PD deficiency, such as those with African or Mediterranean ancestry, be tested for G6PD deficiency before initiation of rasburicase. However, it should be noted that patients of all ancestries may be G6PD deficient. The drug labels do not specifically mention genetic testing, but with the increased availability of genetic test results some patients may be diagnosed with G6PD deficiency preemptively; if so, such definitive results could be used to preclude prescribing of rasburicase and potentially other oxidative drugs even in the absence of G6PD enzyme activity results.

Pediatrics. Much of the evidence relating G6PD deficiency to rasburicase-induced hemolysis and methemoglobinemia was generated in neonates or children (Supplementary Table S7 online), and thus these guidelines apply to neonates, children, and adults.

Please review the complete therapeutic recommendations that are located here: (2).