Rasburicase
FDA Drug Information • Also known as: Elitek
- Brand Names
- Elitek
- Dosage Form
- KIT
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
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 ). Hemolysis: Do not administer Elitek to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Immediately and permanently discontinue Elitek if hemolysis occurs. Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting Elitek therapy ( 4 , 5.2 ). Methemoglobinemia: Elitek can result in methemoglobinemia in some patients. Immediately and permanently discontinue Elitek if methemoglobinemia occurs ( 4 , 5.3 ). Interference with uric acid measurements: Elitek enzymatically degrades uric acid in blood samples left at room temperature. Collect blood samples in prechilled tubes containing heparin and immediately immerse and maintain sample in an ice water bath. Assay plasma samples within 4 hours of collection ( 5.4 ). Hypersensitivity Reactions Elitek can cause serious and fatal hypersensitivity reactions including anaphylaxis. Immediately and permanently discontinue Elitek in patients who experience a serious hypersensitivity reaction [see Contraindications (4) , Warnings and Precautions (5.1) , Adverse Reactions (6.2) ] . Hemolysis Do not administer Elitek to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Immediately and permanently discontinue Elitek in patients developing hemolysis. Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting Elitek [see Contraindications (4) , Warnings and Precautions (5.2) ] . Methemoglobinemia Elitek can result in methemoglobinemia in some patients. Immediately and permanently discontinue Elitek in patients developing methemoglobinemia [see Contraindications (4) , Warnings and Precautions (5.3) ] . Interference with Uric Acid Measurements Elitek enzymatically degrades uric acid in blood samples left at room temperature. Collect blood samples in prechilled tubes containing heparin and immediately immerse and maintain sample in an ice water bath. Assay plasma samples within 4 hours of collection [see Warnings and Precautions (5.4) ] .
Description
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. The drug product is a sterile, white to off-white, lyophilized powder intended for intravenous administration following reconstitution with a diluent. Elitek is supplied in 2 mL or 3 mL and 10 mL colorless, glass vials containing rasburicase at a concentration of 1.5 mg/mL after reconstitution. Elitek 1.5 mg presentation contains 1.5 mg rasburicase, 10.6 mg mannitol, 15.9 mg L-alanine, between 12.6 and 14.3 mg of dibasic sodium phosphate (lyophilized powder), and a diluent (1 mL Water for Injection, USP, and 1 mg Poloxamer 188). Elitek 7.5 mg presentation contains 7.5 mg of rasburicase, 53 mg mannitol, 79.5 mg L-alanine, and between 63 and 71.5 mg dibasic sodium phosphate (lyophilized powder) and a diluent (5 mL Water for Injection, USP, and 5 mg Poloxamer 188).
What Is Rasburicase Used For?
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 acid. ( 1 ) Limitations of use: Elitek is indicated only for a single course of treatment. ( 1 ) Limitations of Use Elitek is indicated only for a single course of treatment [see Warnings and Precautions (5.1) ] .
Dosage and Administration
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. Mix by swirling gently. Do not shake or vortex. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard solution if particulate matter is visible or product is discolored. 2.3 Further Dilution and Administration Administer Elitek as an intravenous infusion only: Inject the calculated dose of reconstituted Elitek solution into an infusion bag containing the appropriate volume of 0.9% sterile sodium chloride, to achieve a final total volume of 50 mL. Infuse over 30 minutes through a separate line or flush line with at least 15 mL of normal saline prior to and after Elitek infusion. Do not use filters during infusion of reconstituted Elitek drug product. Store reconstituted or diluted solution at 2°C–8°C. Discard unused product solution 24 hours following reconstitution.
Side Effects (Adverse Reactions)
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 (5.3) ] Most common adverse reactions (incidence ≥20%), when used concomitantly with anticancer therapy are vomiting, nausea, fever, peripheral edema, anxiety, headache, abdominal pain, constipation, diarrhea, hypophosphatemia, pharyngolaryngeal pain, and increased alanine aminotransferase. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data below reflect exposure to Elitek in 265 pediatric and 82 adult patients enrolled in one active-controlled trial (Study 1), two uncontrolled trials (Studies 2 and 3), and an uncontrolled safety trial (n=82). Additional data were obtained from an expanded access program of 356 patients, for whom data collection was limited to serious adverse reactions. Among these 703 patients 63% were male, the median age was 10 years (range 10 days to 88 years), 73% were Caucasian, 9% African, 4% Asian, and 14% other/unknown. Among the 347 patients for whom all adverse reactions regardless of severity were assessed, the most frequently observed adverse reactions (incidence ≥10%) were vomiting (50%), fever (46%), nausea (27%), headache (26%), abdominal pain (20%), constipation (20%), diarrhea (20%), mucositis (15%), and rash (13%). In Study 1, an active control study, the following adverse reactions occurred more frequently in Elitek-treated subjects than allopurinol-treated subjects: vomiting, fever, nausea, diarrhea, and headache. Although the incidence of rash was similar in the two arms, severe rash was reported only in one Elitek-treated patient. Further studies, including one-active controlled study (Study 4) and four supportive studies, have been conducted in adult patients. In these studies, Elitek was administered to a total of 434 adult patients (58% male, 42% female; median age 56 years [range 18 years to 89 years]; 52% Caucasian, 7% African, 14% Asian, 28% other/unknown). Of these 434 patients, 275 adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomized in an open label trial receiving either Elitek alone, Elitek in combination with allopurinol, or allopurinol alone (Study 4). A drug-related adverse reaction in Study 4 of any grade was experienced in 4.3% of Elitek-treated patients, 5.4% of Elitek/allopurinol-treated patients, and 1.1% of allopurinol-treated patients. Table 1 presents the per-patient incidence of adverse reactions by study arm in Study 4. Table 1: Per-Patient Incidence of Selected Adverse Reactions by Study Arm in Study 4 Adverse Reaction Events were reported and graded according to NCI-CTC version 3.0 and presented as preferred terms MedDRA version 10.1. Elitek (n=92) Elitek/Allopurinol (n=92) Allopurinol (n=91) All Grades % Grades 3,4 % All Grades % Grades 3,4 % All Grades % Grades 3,4 % Overall incidence ≥10% in any Elitek arm and the difference between any Elitek arm versus the allopurinol arm ≥5%. Nausea 57.6 1.1 60.9 1.1 54.9 2.2 Peripheral edema 50 2.2 43.5 3.3 42.9 6.6 Vomiting 38 1.1 37 0 30.8 1.1 Anxiety 23.9 3.3 17.4 0 17.6 0 Abdominal pain 21.7 3.3 33.7 4.3 25.3 2.2 Hypophosphatemia 17.4 4.3 22.8 6.5 16.5 6.6 Hyperbilirubinemia 16.3 3.3 14.1 2.2 7.7 4.4 Pharyngolaryngeal pain...
Drug 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. Plasma samples must be prepared by centrifugation in a precooled centrifuge (4°C). Finally, the plasma must be maintained in an ice water bath and analyzed for uric acid within four hours of collection [see Boxed Warning ] . Rasburicase does not metabolize allopurinol, cytarabine, methylprednisolone, methotrexate, 6-mercaptopurine, thioguanine, etoposide, daunorubicin, cyclophosphamide or vincristine in vitro. No metabolic-based drug interactions are therefore anticipated with these agents in patients.
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. ( 4 ) Glucose-6-phosphate dehydrogenase (G6PD) deficiency. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings in animals, Elitek may cause fetal harm when administered to pregnant women. In animal reproduction studies, intravenous administration of rasburicase to pregnant rabbits during organogenesis at 5-times the human exposure (based on AUC) at the recommended human dose of 0.2 mg/kg resulted in adverse developmental outcomes, including structural abnormalities, embryo-fetal mortality, and alterations to growth (see Data ) . The limited available data with Elitek use in pregnant women are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal fetal outcomes. Consider the benefits and risks of Elitek and possible risks to the fetus when prescribing Elitek to a pregnant woman. The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data Intravenous administration of rasburicase at doses of 10, 20, or 50 mg/kg/day (approximately 14, 34, and 100 times the exposure at the recommended human dose of 0.2 mg/kg) to pregnant rats from gestation days (GD) 6 to 17 produced multiple heart and great vessel malformations at 50 mg/kg/day (approximately 100 times the exposure at the recommended human dose). Intravenous administration of rasburicase from GD 6 to 19 at doses of 2, 10, or 20 mg/kg/day (approximately 5, 26, and 54 times the exposure at the recommended human dose) to pregnant rabbits produced increased pre and postimplantation loss, abortion, decreased uterine weight, decreased fetal body weights, and heart and great vessel malformations at all dose levels.
Overdosage
10 OVERDOSAGE Of the six reported cases of overdosage, five cases had no adverse events reported; nonserious adverse events in the sixth case (a single dose of 1.3 mg/kg) included decreased levels of blood potassium and blood albumin, and increased levels of carbon dioxide, blood lactate dehydrogenase, blood urea, blood phosphorus, blood sodium, and blood alkaline phosphatase. Monitor patients who receive an overdose and initiate supportive measures if required.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied NDC 0024-5150-10: One carton contains 3 single-dose vials each containing 1.5 mg of rasburicase and 3 ampules each containing 1 mL diluent. NDC 0024-5151-75: One carton contains 1 single-dose vial containing 7.5 mg of rasburicase and 1 ampule containing 5 mL diluent. Storage and Handling The lyophilized drug product and the diluent for reconstitution should be stored at 2°C-8°C (36°F-46°F). Do not freeze. Protect from light.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.