Rasburicase in Tumor Lysis Syndrome: Essential Precautions for Patients with  Glucose-6-Phosphate Dehydrogenase (G6PD)

Understanding Rasburicase and G6PD Deficiency: Rasburicase is a widely used medication in the prevention and treatment of tumor lysis syndrome (TLS). However, it is critical to consider potential contraindications when administering Rasburicase, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.   

Rasburicase is a recombinant urate oxidase enzyme that facilitates the breakdown of uric acid into an inactive compound, allantoin. Its primary role is to prevent complications associated with TLS, a condition characterized by rapid cell breakdown and subsequent release of intracellular components. By contrast, G6PD deficiency is an inherited enzyme deficiency that affects red blood cells (RBCs), leading to RBC vulnerability to oxidative stress. G6PD deficiency is more common in certain populations, such as individuals of African, Mediterranean, or Southeast Asian descent, but has been documented in other populations as well (1). 

The link between Rasburicase and G6PD Deficiency: While rasburicase is generally well-tolerated, patients with G6PD deficiency may be at an increased risk of adverse reactions due to the oxidative stress generated during rasburicase treatment. The medication’s mechanism of action involves the generation of hydrogen peroxide, which can potentially cause hemolysis in individuals with G6PD deficiency.  

Precautions and Considerations: Typically, before initiating rasburicase treatment, healthcare professionals would assess patient history of G6PD deficiency or familial traits associated with the condition. Ethnic background and family history are considered since certain populations are considered to have a higher prevalence of G6PD deficiency. However, published evidence shows that it may not advisable to presume G6PD deficiency or lack thereof solely based on race/ethnicity (1). There are several published reports of patients developing hemolytic anemia after administering rasburicase and were later identified to be G6PD deficient (2,3). Unfortunately, despite a rasburicase contraindication to G6PD deficiency, G6PD status is not typically obtained, mainly due to the delays in obtaining assay results from external labs, thereby resulting in the risk of hemolytic anemia and other adverse outcomes.  

G6PD Enzyme Activity Testing: A G6PD assay that measures the activity level of the G6PD enzyme can assist in determining the appropriate course of treatment. A large percentage of hospital laboratories send out whole blood samples to external laboratories for quantitative testing, while some may test using in-house qualitative manual methodologies. G6PD enzymatic activity is provided in Units per grams of hemoglobin (U/g Hb). The turn-around time for the results from external laboratories ranges between 3-5 days, which is typically too late for significant clinical impact. G6PD testing that can be performed in the hospital and provide enzymatic activity (U/g Hb) values in a timely manner is essential before administering rasburicase treatment.