Rasburicase

Brand Names: Elitek

Drug Class: General Prescription

Overview

11 DESCRIPTION Elitek (rasburicase) is a recombinant urate-oxidase produced by a genetically modified Saccharomyces cerevisiae strain. The cDNA coding for rasburicase was cloned from a strain of Aspergillus flavus. Rasburicase is a tetrameric protein with identical subunits. Each subunit is made up of a single 301 amino acid polypeptide chain with a molecular mass of about 34 kDa.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action In humans, uric acid is the final step in the catabolic pathway of purines. Rasburicase catalyzes enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite (allantoin). 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. There was no evidence of a dose response effect on uric acid control for doses between 0.15 and 0.20 mg/kg rasburicase.

Indications

  • 1 INDICATIONS AND USAGE Elitek is indicated for the initial management of plasma uric acid levels in pediatric and 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. Elitek is a recombinant urate-oxidase indicated for initial management of plasma uric acid levels in pediatric and 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...

Common Doses

  • 0.2 mg
  • 1.5 mg
  • 1 mL
  • 7.5 mg

Dosage

2 DOSAGE AND ADMINISTRATION Administer at 0.2 mg/kg as an intravenous infusion over 30 minutes daily for up to 5 days. ( 2.1 ) Do not administer as an intravenous bolus. ( 2.3 ) 2.1 Dosage The recommended dose of Elitek is 0.2 mg/kg as a 30-minute intravenous infusion daily for up to 5 days. Dosing beyond 5 days or administration of more than one course is not recommended. 2.2 Reconstitution Procedure Elitek must be reconstituted with the diluent provided in the carton. Reconstitute the 1.5 mg vial of Elitek with 1 mL of diluent. Reconstitute the 7.5 mg vial of Elitek with 5 mL of diluent.

Black Box Warning

WARNING: HYPERSENSITIVITY REACTIONS, HEMOLYSIS, METHEMOGLOBINEMIA, AND INTERFERENCE WITH URIC ACID MEASUREMENTS WARNING: HYPERSENSITIVITY REACTIONS, HEMOLYSIS, METHEMOGLOBINEMIA, AND INTERFERENCE WITH URIC ACID MEASUREMENTS See full prescribing information for complete boxed warning . Hypersensitivity Reactions: Elitek can cause serious and fatal hypersensitivity reactions including anaphylaxis. Immediately and permanently discontinue Elitek if a serious hypersensitivity reaction occurs ( 4 , 5.1 , 6.2 ).

Contraindications

  • 4 CONTRAINDICATIONS Elitek is contraindicated in patients with a history of anaphylaxis or severe hypersensitivity to rasburicase or in patients with development of hemolytic reactions or methemoglobinemia with rasburicase [see Boxed Warning , Warnings and Precautions (5.1 , 5.2 , 5.3) ] . Elitek is contraindicated in individuals deficient in glucose-6-phosphate dehydrogenase (G6PD) [see Boxed Warning , Warnings and Precautions (5.2) ] . History of the following reactions to rasburicase: anaphylaxis, severe hypersensitivity, hemolysis, methemoglobinemia.

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the prescribing information: Anaphylaxis [see Boxed Warning , Contraindications (4) , Warnings and Precautions (5.1) ] Hemolysis [see Boxed Warning , Contraindications (4) , Warnings and Precautions (5.2) ] Methemoglobinemia [see Boxed Warning , Contraindications (4) , Warnings and Precautions (5.

Interactions

  • 7 DRUG INTERACTIONS Laboratory Test Interference At room temperature, Elitek causes enzymatic degradation of the uric acid in blood/plasma/serum samples potentially resulting in spuriously low plasma uric acid assay readings. The following special sample handling procedure must be followed to avoid ex vivo uric acid degradation. Uric acid must be analyzed in plasma. Blood must be collected into prechilled tubes containing heparin anticoagulant. Immediately immerse plasma samples for uric acid measurement in an ice water bath.