Elitek

• Hypersensitivity Reactions: Elitek can cause serious and fatal hypersensitivity reactions including anaphylaxis. Immediately and permanently discontinue Elitek if a serious hypersensitivity reaction occurs (

  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.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

  ,

  5.1 Hypersensitivity Reactions

  Elitek can cause serious and fatal hypersensitivity reactions including anaphylaxis. In clinical studies, anaphylaxis was reported in <1% patients receiving Elitek. This can occur at any time during treatment including the first dose. Signs and symptoms of these reactions include bronchospasm, chest pain and tightness, dyspnea, hypoxia, hypotension, shock, and urticaria. Immediately and permanently discontinue Elitek administration in any patient developing clinical evidence of a serious hypersensitivity reaction

  [see Boxed Warning, Contraindications (4), Adverse Reactions (6.2)]

  .

  The safety and efficacy of Elitek have been established only for a single course of treatment once daily for 5 days.

  ,

  6.2 Immunogenicity

  As with all therapeutic proteins, there is potential for immunogenicity. Elitek can elicit antiproduct antibodies that bind to rasburicase and in some instances inhibit the activity of rasburicase in vitro

  [see Boxed Warning, Warnings and Precautions (5.1)]

  .

  In clinical trials of pediatric patients with hematologic malignancies, 24/218 patients tested (11%) developed antibodies by day 28 following Elitek administration as assessed by qualitative ELISA.

  Using quasi-quantitative immunoassays in rasburicase-naive adult patients with hematological malignancies, 47/260 (18%) patients were positive for anti-rasburicase immunoglobulin G (IgG), 21/260 (8%) patients were positive for anti-rasburicase neutralizing IgG, and 16/260 (6%) patients were positive for anti-rasburicase immunoglobulin E (IgE) from day 14 to 24 months after 5 daily doses of Elitek.

  The incidence of antibody responses detected is highly dependent on the sensitivity and specificity of the assay, which have not been fully evaluated. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors, including serum sampling, timing and methodology, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Elitek with the incidence of antibodies to other products may be misleading.

  ).
• 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 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.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

  ,

  5.2 Hemolysis

  Elitek is contraindicated in patients with G6PD deficiency because hydrogen peroxide is one of the major by-products of the conversion of uric acid to allantoin. In clinical studies, hemolysis occurs in <1% patients receiving Elitek; severe hemolytic reactions occurred within 2–4 days of the start of Elitek. Immediately and permanently discontinue Elitek administration in any patient developing hemolysis. Institute appropriate patient monitoring and support measures (e.g., transfusion support). Screen patients at higher risk for G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to starting Elitek

  [see Boxed Warning, Contraindications (4)]

  .

  ).
• Methemoglobinemia: Elitek can result in methemoglobinemia in some patients. Immediately and permanently discontinue Elitek if methemoglobinemia occurs (

  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.
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

  ,

  5.3 Methemoglobinemia

  In clinical studies, methemoglobinemia occurred in <1% patients receiving Elitek. These included cases of serious hypoxemia requiring intervention with medical support measures. It is not known whether patients with deficiency of cytochrome b₅reductase (formerly known as methemoglobin reductase) or of other enzymes with antioxidant activity are at increased risk for methemoglobinemia or hemolytic anemia. Immediately and permanently discontinue Elitek administration in any patient identified as having developed methemoglobinemia. Institute appropriate monitoring and support measures (e.g., transfusion support, methylene-blue administration)

  [see Boxed Warning, Contraindications (4)]

  .

  ).
• 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 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. Special sample handling procedure must be followed to avoid ex vivo uric acid degradation

  [see Boxed Warning, Drug Interactions (7)]

  .

  ).

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.

• Administer at 0.2 mg/kg as an intravenous infusion over 30 minutes daily for up to 5 days. (
  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.
  )
• Do not administer as an intravenous bolus. (
  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.
  )

• For injection: 1.5 mg, lyophilized powder in single-dose vial for reconstitution
• For injection: 7.5 mg, lyophilized powder in single-dose vial for reconstitution

• Pregnancy: May cause fetal harm. (
  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.
  )
• Lactation: Breastfeeding not recommended. (
  8.2 Lactation

  Risk Summary

  There are no available data on the presence of rasburicase in human breast milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with Elitek, and for 2 weeks after the last dose.
  )