Rasburicase

Serious side effects have been reported with rasburicase.

• Rasburicase may cause a severe allergic reaction. If you experience any of the following symptoms, contact your doctor immediately: chest pain or tightness, shortness of breath, lightheadedness, faintness, or hives.
• Rasburicase injection may cause serious blood problems. Tell your doctor if you have glucose-6-phosphate dehydrogenase (G6PD) deficiency (an inherited blood disease). Your doctor will probably tell you that you cannot receive rasburicase. Also tell your doctor if you are of African or Mediterranean descent. If you experience any of the following symptoms, contact your doctor immediately: headache; shortness of breath; lightheadedness; weakness; confusion; fast, pounding, or irregular heartbeat; seizures; pale or blue-gray skin color; yellowing of the skin or eyes; chills; extreme tiredness; and dark urine.
• Rasburicase can result in methemoglobinemia in some patients. This is a blood disorder in which an abnormal amount of methemoglobin (a protein in the blood) is made. This medication should be stopped if methemoglobinemia occurs. Signs of methemoglobinemia are a bluish coloring of the skin, headache, fatigue, shortness of breath, and lack of energy.

Do not take this medication if you:

• are allergic to rasburicase or to any of its ingredients
• have developed blood disorders or methemoglobinemia while on rasburicase
• have a glucose-6-phosphate dehydrogenase (G6PD)

Rasburicase comes as a solution (liquid) to be injected intravenously (into a vein) by a healthcare professional. It is usually given over a period of 30 minutes once a day for up to 5 days. This medication is given as a single course of treatment that will not be repeated.

Call your doctor for instructions if you miss an appointment for your rasburicase injection.

Other drugs may interact with rasburicase, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

General

• Initiate chemotherapy 4–24 hours after administering first dose of rasburicase.1

• Administer concomitantly with IV hydration according to standard medical practice for management of plasma uric acid in patients at risk for tumor lysis syndrome.1

Administration

IV Administration

Administer by IV infusion.1

Do not administer as a rapid IV injection (e.g., IV push or bolus).1

Do not use filters during administration.1

Infuse through a different line than that used for other concomitant drugs; if not possible, flush the line with at least 15 mL of 0.9% sodium chloride injection prior to and after infusion of rasburicase solutions.1

Reconstitute prior to administration.1

Determine number of vials needed to achieve the proper dosage based on the patient’s weight and the dose per kg.1

Reconstitute vial containing 1.5 mg of rasburicase lyophilized powder with 1 mL of provided diluent (sterile water for injection and poloxamer 188) to provide a solution containing 1.5 mg of rasburicase per mL.1

Mix by swirling very gently.1 Do not shake or form a vortex.1

Must be diluted further before IV administration.a

Use strict aseptic technique since drug product contains no preservatives.1

Withdraw appropriate dose from reconstituted vials and add to the appropriate volume of 0.9% sodium chloride injection to achieve a final volume of 50 mL.1

Administer diluted solution by IV infusion over 30 minutes.1

Dosage

Pediatric Patients

Infants and children 1 month to 17 years of age: 0.15 or 0.2 mg/kg once daily for 5 days.1

Safety and efficacy established only for a single course of treatment.1 (See Sensitivity Reactions under Cautions.)

Prescribing Limits

Pediatric Patients

Infants and children 1 month to 17 years of age: Safety and efficacy of twice daily dosing, dosing for >5 days, or administration of >1 course of therapy not established.1

Special Populations

No special populations dosing recommendations at this time.1

Pharmacokinetics evaluated in pediatric patients; insufficient data available to evaluate pharmacokinetics in adults.1

Absorption

Onset

Age-adjusted target plasma uric acid concentrations (i.e., ≤6.5 mg/dL in children <13 years of age or ≤7.5 mg/dL in those ≥13 years of age) achieved within 48 hours following initiation of rasburicase therapy.1 3

Duration

Target plasma uric acid concentrations maintained for 24 hours after the last administered rasburicase dose.1 3

Distribution

Extent

Not known whether rasburicase is distributed into milk.a

Elimination

Half-life

18 hours.a

• If you have an allergy to rasburicase or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding or plan to breast-feed.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take rasburicase with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of methemoglobinemia like a blue or gray color of the lips, nails, or skin; a heartbeat that does not feel normal; seizures; very bad dizziness or passing out; very bad headache; feeling very sleepy; feeling tired or weak; or shortness of breath.
• Chest pain or pressure.
• Shortness of breath.
• Very bad dizziness or passing out.
• Feeling very tired or weak.
• Yellow skin or eyes.
• Dark urine.
• Pale skin.
• Swelling in the arms or legs.
• Fever.
• Coughing up blood.

• Enzyme
• Enzyme, Urate-Oxidase (Recombinant)

There are no dosage adjustments provided in the manufacturer’s labeling.

IV infusion over 30 minutes; do not administer as a bolus infusion. Do not filter during infusion. If not possible to administer through a separate line, IV line should be flushed with at least 15 mL saline prior to and following rasburicase infusion.

The optimal timing of rasburicase administration (with respect to chemotherapy administration) is not specified in the US labeling. In some studies, chemotherapy was administered 4 to 24 hours after the first rasburicase dose (Cortes 2010; Kikuchi 2009; Vadhan-Raj 2012); however, rasburicase generally may be administered irrespective of chemotherapy timing.

There are no known significant interactions.

Plasma uric acid levels (4 hours after rasburicase administration, then every 6 to 8 hours until TLS resolution), CBC, G6PD deficiency screening (in patients at high risk for deficiency); monitor for hypersensitivity reactions

Commonly reported side effects of rasburicase include: abdominal pain, fever, headache, nausea, and vomiting. See below for a comprehensive list of adverse effects.

0.2 mg/kg as a 30-minute IV infusion once a day for up to 5 days

Comments:
-Use beyond 5 days or administration of more than 1 course of therapy is not recommended; the exact duration should be based upon adequate monitoring of uric acid levels in plasma and clinical judgement.

Use: For the initial management of plasma uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving chemotherapy expected to result in tumor lysis and subsequent elevation of plasma uric acid; this drug is only approved for a single course of treatment.

No adjustment recommended