RasburicaseEdit

Rasburicase is a medication that plays a critical role in the management of high uric acid levels associated with cancer therapies, particularly in the context of tumor lysis syndrome. It is a recombinant enzyme that rapidly reduces uric acid in the bloodstream by converting it to a more soluble compound, facilitating excretion. The drug is used to prevent or treat hyperuricemia in patients at risk for TLS and in some settings with established hyperuricemia.

Rasburicase is a recombinant form of urate oxidase, an enzyme that does not occur in humans but is found in several other organisms. The enzyme catalyzes the oxidation of uric acid to allantoin, a compound that is more readily excreted by the kidneys. This mechanism makes rasburicase different from xanthine oxidase inhibitors, which attempt to limit the production of uric acid rather than accelerate its breakdown. In clinical practice, this rapid action can help avert uric acid–related kidney injury in patients undergoing aggressive chemotherapy or radiotherapy. For more on the biochemical context, see urate oxidase and uric acid.

Medical uses

Rasburicase is indicated for the treatment and prevention of hyperuricemia in patients undergoing initial therapy for cancers associated with a high risk of TLS, and in patients with established TLS who have elevated uric acid. It is used as part of a broader strategy to protect renal function during cancer treatment, alongside hydration and other supportive measures. In some guidelines, rasburicase is positioned as an alternative or adjunct to allopurinol, which reduces uric acid production but does not directly lower existing uric acid as quickly. See discussions in clinical guidelines such as National Comprehensive Cancer Network and European Society for Medical Oncology.

Mechanism of action

Rasburicase is a recombinant enzyme derived from non-human sources and produced through modern biotechnology. It acts by oxidizing uric acid to allantoin, a more water-soluble metabolite readily eliminated by the kidneys. This action lowers serum uric acid concentrations rapidly, which helps prevent precipitation of uric acid in renal tubules and supports kidney function during tumor cell breakdown. In addition to lowering uric acid, rasburicase reduces the risk of urate nephropathy in high-risk patients. For background on the relevant substrates and products, see uric acid and allantoin.

Pharmacology and administration

Dosing regimens commonly used in practice include a single intravenous dose of 0.2 mg/kg, infused over a short period, for TLS prophylaxis or treatment. In some high-risk scenarios, clinicians may administer rasburicase once daily for up to 5 days, depending on uric acid levels and patient response. See product labeling for specifics.
The drug is administered intravenously and requires careful monitoring of uric acid levels, liver and kidney function, and potential adverse effects.
Rasburicase is contraindicated in individuals with known glucose-6-phosphate dehydrogenase (G6PD) deficiency due to the risk of hemolysis and methemoglobinemia. Because G6PD deficiency prevalence varies by population, testing or careful assessment of risk may be considered in certain settings. See glucose-6-phosphate dehydrogenase deficiency for context.

Safety and adverse effects

Common adverse effects are generally mild to moderate and may include hypersensitivity reactions, fever, nausea, and abdominal pain. More serious but less common risks include anaphylaxis and hemolytic events in individuals with G6PD deficiency. Because rasburicase generates hydrogen peroxide as part of its enzymatic activity, there is a theoretical concern for oxidative stress in susceptible patients. The possibility of the development of antibodies to the enzyme over time has been observed, which can influence effectiveness in some individuals. Clinicians weigh these risks against the potential benefit in patients with TLS or extreme hyperuricemia, particularly when rapid uric acid reduction is clinically important. See anaphylaxis and hemolysis for general discussions of these risks.

History and regulatory status

Rasburicase was developed to address the urgent need for rapid uric acid reduction in TLS. It was approved for clinical use in the early 2000s and has since become part of standard oncologic care in many countries. Brand names in various markets include Elitek, among others. The medication is subject to national regulatory frameworks and may appear on formulary lists and cancer care guidelines worldwide. See FDA approval history and drug development processes for context.

Economic and access considerations

The use of rasburicase must be balanced against cost considerations, as it is more expensive than many alternatives that reduce uric acid production rather than remove existing uric acid. In practice, rasburicase is often reserved for patients at high risk of TLS or who do not respond adequately to initial management with hydration and allopurinol. Health systems and institutions evaluate cost-effectiveness, often using metrics such as the expected reduction in hospital stay, avoidance of renal replacement therapy, and overall outcomes. See cost-effectiveness analyses and healthcare economics discussions for related topics.

Controversies and debates

Cost versus benefit: Critics point to the high price of rasburicase relative to traditional approaches, arguing that its routine use should be limited to patients at substantial risk of TLS or those who cannot tolerate alternative therapies. Proponents emphasize the potential to prevent renal failure and shorten hospitalizations, hoping to justify the expense in high-stakes clinical scenarios. The debate is reflected in guidelines and institutional policies that differ by country and by health system.
G6PD deficiency and population risk: The contraindication in G6PD deficiency prompts discussion about screening strategies, especially in populations with higher prevalence of deficiency. Some argue for universal testing in high-risk settings, while others favor targeted approaches based on epidemiology and resource constraints.
Access and equity: As with many high-cost oncologic therapies, disparities in access can influence outcomes. Debates encompass how to allocate limited resources, ensure timely treatment, and balance investment in rasburicase with other supportive care measures.
Alternatives and sequencing: The relative roles of rasburicase and allopurinol, as well as the use of hydration and emergency dialysis in TLS, are topics of ongoing clinical discussion. In some patients, a staged approach using allopurinol first, followed by rasburicase if uric acid remains elevated, is discussed in guidelines and among clinicians, depending on risk stratification.