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FDA Approval for Rasburicase

Brand name(s): Elitek®

  • Approved for initial management of plasma uric acid levels in adults with leukemia, lymphoma, and solid tumors receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

On October 16, 2009, the Food and Drug Administration (FDA) granted approval for the use of rasburicase (Elitek®, made by Sanofi-aventis, U.S.) for the initial management of plasma uric acid levels in adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid. The approval was based on results from the EFC 4978 trial which demonstrated a significant improvement in uric acid response rates (the proportion of patients with plasma uric acid levels less than 7.5 mg/dL from day three through day seven following initiation of antihyperuricemic treatment) among rasburicase-treated patients compared to allopurinol-treated patients.

Clinical trial EFC 4978 was a randomized (1:1:1), multicenter, open-label trial conducted in patients with leukemia, lymphoma, and solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS). A total of 275 adult patients received at least one dose of trial drug. The median age was 56 years; 62 percent were males; 66 percent had leukemia; 29 percent had lymphoma; and 18 percent were hyperuricemic (uric acid at least 7.5mg/dL) at entry. Patients in Arm A received rasburicase for 5 days (n=92). Patients in Arm B received rasburicase from day one through day three followed by oral allopurinol from day three through day five (overlap on day three: rasburicase and allopurinol administered approximately 12 hours apart) (n=92). Patients in Arm C received oral allopurinol for five days (n=91). Rasburicase was administered at the dose of 0.2 mg/kg/day as a 30-minute infusion once daily. Allopurinol was administered orally at the dose of 300 mg once a day. The main outcome measure of this trial was the uric acid response rate, as described above.

The uric acid response rate in patients in Arm A receiving rasburicase was 87 percent versus 66 percent uric acid response rate in patients in Arm C receiving allopurinol. (p=0.0009). No significant difference in the uric acid response rates were noted between Arms B and C. There was no difference between the arms in the incidence of TLS.

The adverse reactions related to rasburicase observed during the EFC 4978 trial were consistent in nature and severity to the labeled adverse reactions.

Serious adverse reactions occurring at a difference in incidence of at least two percent in patients receiving rasburicase compared to patients receiving allopurinol in randomized trials included pulmonary hemorrhage, respiratory failure, cardiac (supraventricular) arrhythmias, ischemic coronary artery disorders, and abdominal and gastrointestinal infections. The incidence of anaphylactic shock, hemolysis (lysis of red blood cells), and methemoglobinemia (presence of higher than normal levels of a form of hemoglobin that doesn't bind oxygen) occurred in less than one percent of the 887 patients treated with rasburicase in clinical trials.

The most common toxicities occurring at an overall incidence at least ten percent with the largest difference between the rasburicase arm versus the allopurinol arm in the EFC 4978 trial included peripheral edema (50 percent), vomiting (38 percent), hyperbilirubinemia (excess bilirubin, a breakdown product of heme, in the blood) (16 percent), sepsis (12 percent), and fluid overload (12 percent).

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

  • Updated: July 3, 2013