What is the effect of rasburicase (uric acid oxidase) on uric acid levels?

From the Guidelines

When calculating uric acid levels in patients receiving rasburicase, it is crucial to handle blood samples with special precautions to prevent falsely low results, as rasburicase continues to break down uric acid in the collection tube at room temperature, potentially masking true hyperuricemia. To accurately measure uric acid levels, blood samples should be collected in pre-chilled tubes containing heparin anticoagulant, immediately placed on ice, and processed within 4 hours of collection, as recommended by studies such as 1. The laboratory should be specifically notified that the patient is on rasburicase therapy to ensure proper handling and analysis of the sample.

Some key points to consider when calculating uric acid levels in patients on rasburicase include:

• Collecting blood in pre-chilled tubes containing heparin anticoagulant to prevent uric acid breakdown
• Immediately placing the samples on ice to slow down the enzymatic reaction
• Processing the samples within 4 hours of collection to minimize the effect of rasburicase on uric acid levels
• Notifying the laboratory that the patient is on rasburicase therapy to ensure proper sample handling and analysis

Rasburicase works by converting uric acid to allantoin, which is more soluble and readily excreted by the kidneys, as described in studies such as 1 and 1. This enzymatic reaction continues ex vivo unless the sample is properly handled, which can lead to artificially low measurements if precautions are not taken. For accurate monitoring of patients on rasburicase therapy, especially those with tumor lysis syndrome, proper sample handling is essential for clinical decision-making regarding treatment duration and efficacy.

In terms of treatment, rasburicase should be administered at a dose of 0.20 mg/kg/day, infused over 30 minutes, with the first dose given at least four hours before the start of tumor-specific therapy, and continued for at least 3-5 days, as recommended by 1. It is also important to note that rasburicase is contraindicated in patients with metahemoglobinemia, G6PDH deficiency, or other metabolic disorders that can potentially cause hemolytic anemia, and these patients should be treated with oral allopurinol, hydration, and urine alkalinization instead.

From the FDA Drug Label

12.2 Pharmacodynamics The measurement of plasma uric acid was used to evaluate the effectiveness of rasburicase in clinical studies. Following administration of either 0.15 or 0.20 mg/kg rasburicase daily for up to 5 days, plasma uric acid levels decreased within 4 hours and were maintained below 7.5 mg/dL in 98% of adult and 90% of pediatric patients for at least 7 days.

The uric acid level when on rasburicase is expected to be below 7.5 mg/dL in most patients, with a decrease in plasma uric acid levels within 4 hours of administration. This is based on clinical studies where patients received either 0.15 or 0.20 mg/kg rasburicase daily for up to 5 days 2, 2.

• Key points:
  • Decrease in plasma uric acid levels within 4 hours
  • Uric acid levels maintained below 7.5 mg/dL for at least 7 days in most patients
  • Effective in both adult and pediatric patients

From the Research

Uric Acid Levels on Rasburicase

• The administration of rasburicase has been shown to effectively decrease uric acid levels in patients with hyperuricemia or at risk for tumor lysis syndrome (TLS) 3, 4, 5, 6, 7.
• A study published in 2010 found that a single dose of 6 mg rasburicase decreased median uric acid levels from 9.2 mg/dL to 1.8 mg/dL by day 3 in a high-risk population 3.
• Another study from 2015 reported that fixed, low-dose rasburicase (3 mg, 4.5 mg, or 6 mg) produced a consistent lowering of uric acid levels, with a median reduction of 5.5-10.05 mg/dL 24 hours post-dose 4.
• A pilot randomized clinical trial in 2009 demonstrated that a single dose of 4.5 mg rasburicase reduced serum uric acid levels and improved renal function in elderly patients with hyperuricemia 5.
• Case reports have also shown that a single dose of rasburicase can be effective in treating hyperuricemia in acute kidney injury, with a decline in serum uric acid levels and increased urine output 6.
• Rasburicase has been approved for the treatment and prevention of hyperuricemia in patients with hematologic malignancies, offering a rapid onset of action and the ability to lower preexisting elevated uric acid levels 7.

Dosage and Administration

• The labeled dose of rasburicase is 0.2 mg/kg/day administered intravenously over 30 minutes for up to 5 days 3.
• Institutional guidelines may recommend fixed doses of rasburicase, such as 6 mg for uric acid levels >8 mg/dL or 4-8 mg/dL in high-risk patients, with repeat dosing indicated for uric acid levels >4 mg/dL determined ≥12 hours following the initial dose 3.
• Fixed, low-dose rasburicase (3 mg, 4.5 mg, or 6 mg) has been shown to be effective in lowering uric acid levels, with the choice of dose depending on the patient's baseline uric acid level and risk factors for TLS 4.