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Drug: Rasburicase - Elitek™

Usual Diluents

Dilution Data

DILUTION SUMMARY

[Amount of drug] [Infusion volume] [Infusion rate]

[Prescribed dose] [50ml (total volume )] [30 minutes]

-Reconstitute with supplied diluent (see section below).

Do not administer Elitek as a bolus injection.
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 reconstitution or infusion of Elitek.

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.
Inspect reconstituted Elitek visually for particulate matter and discoloration prior to administration. Discard solution if particulate matter is visible or product is discolored.

Further Dilution and Administration

Do not administer Elitek as a bolus injection.
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 reconstitution or infusion of Elitek.
Store reconstituted or diluted solution at 2–8°C.
Discard unused product solution 24 hours following reconstitution.

The lyophilized drug product and the diluent for reconstitution should be stored at 2–8°C (36–46°F). Do not freeze. Protect from light.

Stability / Miscellaneous

WARNINGS	CLINICAL PHARMACOLOGY	INDICATIONS
CONTRAINDICATIONS	DOSAGE AND ADMINISTRATION	RECONSTITUTION / DILUTION
	HOW SUPPLIED
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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 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).

CLINICAL PHARMACOLOGY

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).

WARNINGS
ANAPHYLAXIS, HEMOLYSIS, METHEMOGLOBINEMIA, AND INTERFERENCE WITH URIC ACID MEASUREMENTS

Anaphylaxis
Elitek® can cause severe 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 pre-chilled 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)].

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 anti-cancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid.

Limitation of use: Elitek is indicated only for a single course of treatment [see Warnings and Precautions (5.1)].

2. DOSAGE AND ADMINISTRATION

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.
Inspect reconstituted Elitek visually for particulate matter and discoloration prior to administration. Discard solution if particulate matter is visible or product is discolored

2.3 Further Dilution and Administration

Do not administer Elitek as a bolus injection.
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 reconstitution or infusion of Elitek.
Store reconstituted or diluted solution at 2–8°C.
Discard unused product solution 24 hours following reconstitution

3. DOSAGE FORMS AND STRENGTHS
1.5 mg powder per single-use vial
7.5 mg powder per single-use vial

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)].

Elitek is contraindicated in individuals deficient in glucose-6-phosphate dehydrogenase (G6PD) [see Boxed Warning, Warnings and Precautions (5.2)].

5. WARNINGS AND PRECAUTIONS

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

Elitek can cause severe allergic 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)].

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)].

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 b5 reductase (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)].

5.4 Laboratory Sample Handling Procedure
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 pre-chilled 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 pre-cooled 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].

HOW SUPPLIED/STORAGE AND HANDLING
How Supplied

NDC 0024-5150-10: One carton contains 3 single-use 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-use 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 2–8°C (36–46°F). Do not freeze. Protect from light.

Mfd. at Hospira, Inc.
Mfd. for sanofi-aventis U.S. LLC