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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(ras BYOOR i kayse)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Initial management of uric acid levels in patients with leukemia, lymphoma, and solid tumor malignancies receiving chemotherapy expected to result in tumor lysis and elevation of plasma uric acid
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse effects were observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
Contraindications
History of anaphylaxis or severe hypersensitivity to rasburicase or any component of the formulation; history of hemolytic reaction or methemoglobinemia associated with rasburicase; glucose-6-phosphatase dehydrogenase (G6PD) deficiency
Warnings/Precautions
Boxed warnings:
• Hemolysis: See “Concerns related to adverse effects” below.
• Hypersensitivity/anaphylactoid reactions: See “Concerns related to adverse effects” below.
• Methemoglobinemia: See “Concerns related to adverse effects” below.
• Uric acid degradation: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Hypersensitivity/anaphylactoid reactions: [U.S. Boxed Warning]: Severe hypersensitivity reactions (including anaphylaxis) have been reported; immediately and permanently discontinue in patients developing serious hypersensitivity reaction. Reactions may occur at any time during treatment (including the initial dose); signs and symptoms may include bronchospasm, chest pain/tightness, dyspnea, hypotension, hypoxia, shock, or urticaria.
• Hemolysis: [U.S. Boxed Warning]: Due to the risk for hemolysis (<1%), rasburicase is contraindicated in patients with G6PD deficiency. Discontinue immediately and permanently in any patient developing hemolysis. Patients at higher risk for G6PD deficiency (eg, African, Mediterranean, or Southeast Asian descent) should be screened prior to therapy. Severe hemolytic reactions occurred within 2-4 days of rasburicase initiation.
• Methemoglobinemia: [U.S. Boxed Warning]: Methemoglobinemia has been reported (<1%). Discontinue immediately and permanently in any patient developing methemoglobinemia. Initiate appropriate treatment (eg, transfusion, methylene blue) if methemoglobinemia occurs.
Other warnings/precautions:
• Hydration: Patients at risk for tumor lysis syndrome should receive appropriate I.V. hydration as part of uric acid management; however, alkalinization (with sodium bicarbonate) concurrently with rasburicase is not recommended (Coiffier, 2008).
• Multiple courses: Rasburicase is immunogenic and can elicit an antibody response; administration of more than one course is not recommended.
• Uric acid degradation: [U.S. Boxed Warning]: Enzymatic degradation of uric acid in blood samples will occur if left at room temperature, which may interfere with serum uric acid measurements; specific guidelines for the collection of plasma uric acid samples must be followed, including collection in prechilled tubes with heparin anticoagulant, immediate ice water bath immersion and assay within 4 hours.
Adverse Reactions
>10%:
Cardiovascular: Peripheral edema (≤50%), fluid overload (≤12%)
Central nervous system: Fever (46%; serious: 5%), headache (26%), anxiety (≤24%)
Dermatologic: Rash (13%; serious: 1%)
Endocrine & metabolic: Hypophosphatemia (≤17%)
Gastrointestinal: Vomiting (50%), nausea (27%), abdominal pain (20%), constipation (20%), diarrhea (20%), mucositis (15%; serious: 2%)
Hepatic: Hyperbilirubinemia (≤16%), ALT increased (≤11%)
Respiratory: Pharyngolaryngeal pain (≤14%)
Miscellaneous: Antibody formation (healthy volunteers: 61% to 64%; patients with malignancies: 11%), sepsis (≤12%; serious: 3% to 5%)
1% to 10%:
Cardiovascular: Ischemic coronary disorder, supraventricular arrhythmia
Endocrine & metabolic: Hyperphosphatemia (≤10%)
Gastrointestinal: Abdominal/gastrointestinal infection
Hematologic: Neutropenic fever (serious: 4%), neutropenia (serious: 2%)
Respiratory: Respiratory distress (serious: 3%), pulmonary hemorrhage, respiratory failure
Miscellaneous: Hypersensitivity (≤4%)
<1%, postmarketing, and/or case reports: Acute renal failure, anaphylaxis, arrhythmia, cardiac arrest, cardiac failure, cellulitis, cerebrovascular disorder, chest pain, cyanosis, dehydration, hemolysis, hemorrhage, hot flashes, ileus, infection, intestinal obstruction, liver enzymes increased, methemoglobinemia, MI, pancytopenia, paresthesia, pneumonia, pulmonary edema, pulmonary hypertension, retinal hemorrhage, rigors, seizure, thrombosis, thrombophlebitis
Metabolism/Transport Effects
None known.
Drug Interactions
There are no known significant interactions.
Storage
Prior to reconstitution, store with diluent at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Reconstituted and final solution may be stored up to 24 hours at 2°C to 8°C (36°F to 46°F). Discard unused product.
Reconstitution
Reconstitute with provided diluent (use 1 mL diluent for the 1.5 mg vial and 5 mL diluent for the 7.5 mg vial). Mix by gently swirling; do not shake or vortex. Discard if discolored or containing particulate matter. Total dose should be further diluted in NS to a final volume of 50 mL.
Mechanism of Action
Rasburicase is a recombinant urate-oxidase enzyme, which converts uric acid to allantoin (an inactive and soluble metabolite of uric acid); it does not inhibit the formation of uric acid.
Pharmacodynamics/Kinetics
Onset: Uric acid levels decrease within 4 hours of initial administration
Distribution: Children: 110-127 mL/kg; Adults: 76-138 mL/kg
Half-life elimination: ~16-23 hours
Dosage
I.V.: Hyperuricemia associated with malignancy:
Children: 0.2 mg/kg once daily for up to 5 days (manufacturer-recommended dose) or
Alternate dosing (unlabeled; Coiffier, 2008): 0.05-0.2 mg/kg once daily for 1-7 days (average of 2-3 days) with the duration of treatment dependent on plasma uric acid levels and clinical judgment (patients with significant tumor burden may require an increase to twice daily); the following dose levels are recommended based on risk of tumor lysis syndrome (TLS):
High risk: 0.2 mg/kg once daily (duration is based on plasma uric acid levels)
Intermediate risk: 0.15 mg/kg once daily (duration is based on plasma uric acid levels); may consider managing initially with a single dose
Low risk: 0.1 mg/kg once daily (duration is based on clinical judgment); a dose of 0.05 mg/kg was used effectively in one trial
Single-dose rasburicase (unlabeled use; based on limited data): 0.15 mg/kg; additional doses may be needed based on serum uric acid levels (Liu, 2005)
Adults: 0.2 mg/kg once daily for up to 5 days (manufacturer-recommended dose) or
Alternate dosing (unlabeled; Coiffier, 2008): 0.05-0.2 mg/kg once daily for 1-7 days (average of 2-3 days) with the duration of treatment dependent on plasma uric acid levels and clinical judgment (patients with significant tumor burden may require an increase to twice daily); the following dose levels are recommended based on risk of tumor lysis syndrome (TLS):
High risk: 0.2 mg/kg once daily (duration is based on plasma uric acid levels)
Intermediate risk: 0.15 mg/kg once daily (duration is based on plasma uric acid levels)
Low risk: 0.1 mg/kg once daily (duration is based on clinical judgment); a dose of 0.05 mg/kg was used effectively in one trial
Single-dose rasburicase (unlabeled use; based on limited data): 0.15 mg/kg (Campara, 2009; Liu, 2005) or 3-7.5 mg as a single dose (Hutcherson, 2006; McDonnell, 2006; Reeves, 2008; Trifilio, 2006); repeat doses (1.5-6 mg) may be needed based on serum uric acid levels
Administration: I.V.
I.V. 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, I.V. line should be flushed with at least 15 mL saline prior to and following rasburicase infusion. May begin chemotherapy 4 hours after the initiation of rasburicase (Coiffier, 2008).
Monitoring Parameters
Plasma uric acid levels (4 hours after rasburicase administration, then every 6-8 hours until TLS resolution), CBC, G6PD deficiency screening (in patients at high risk for deficiency); monitor for hypersensitivity
Test Interactions
Specific handling procedures must be followed to prevent the degradation of uric acid in plasma samples. Blood must be collected in prechilled tubes containing heparin anticoagulant. Samples must then be immediately immersed in an ice water bath. Prepare samples by centrifugation in a precooled centrifuge (4°C). Samples must be kept in ice water bath and analyzed within 4 hours of collection.
Patient Education
This medication can only be administered by infusion; you will be monitored closely during and following infusion. Report immediately any swelling or any signs of allergic reaction (eg, respiratory difficulty or swallowing, back pain, chest tightness, rash, hives, swelling of lips or mouth). Report severe headache, persistent gastrointestinal upset (nausea, vomiting, or abdominal pain), respiratory difficulty, or swelling of extremities.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Mucositis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
GI side effects are common; use caution with SSRIs. May cause neutropenia; use caution with clozapine.
Nursing: Physical Assessment/Monitoring
Evaluate carefully for use-related cautions prior to instituting therapy. Patient must be observed closely for hypersensitivity reaction.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Elitek®: 1.5 mg, 7.5 mg [supplied with diluent]
References
Arnold TM, Reuter JP, Delman BS, et al, “Use of Single-Dose Rasburicase in an Obese Female,” Ann Pharmacother, 2004, 38(9):1428-31.
Campara M, Shord SS, and Haaf CM, “Single-Dose Rasburicase for Tumour Lysis Syndrome in Adults: Weight-Based Approach,” J Clin Pharm Ther, 2009, 34(2):207-13.
Coiffier B, Altman A, Pui CH, et al, “Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review,” J Clin Oncol, 2008, 26(16):2767-78.
Coiffier B, Mounier N, Bologna S, et al, “Efficacy and Safety of Rasburicase (Recombinant Urate Oxidase) for the Prevention and Treatment of Hyperuricemia During Induction Chemotherapy of Aggressive Non-Hodgkin's Lymphoma: Results of GRAALI (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) Study,” J Clin Oncol, 2003, 21(23):4402-6.
Hutcherson DA, Gammon DC, Bhatt MS, et al, “Reduced-Dose Rasburicase in the Treatment of Adults With Hyperuricemia Associated With Malignancy,” Pharmacother, 2006, 26(2):242-7.
Jeha S, Kantarjian H, Irwin D, et al, “Efficacy and Safety of Rasburicase, a Recombinant Urate Oxidase (Elitek), in the Management of Malignancy-Associated Hyperuricemia in Pediatric and Adult Patients: Final Results of a Multicenter Compassionate Use Trial,” Leukemia, 2005, 19(1):34-8.
Lee AC, Li CH, So KT, et al, “Treatment of Impending Tumor Lysis With Single-Dose Rasburicase,” Ann Pharmacother, 2003, 37(11):1614-7.
Liu CY, Sims-McCallum RP, and Schiffer CA, “A Single Dose of Rasburicase is Sufficient for the Treatment of Hyperuricemia in Patients Receiving Chemotherapy,” Leuk Res, 2005, 29(4):463-5.
McDonnell AM, Lenz KL, Frei-Lahr DA, et al, “Single-Dose Rasburicase 6 mg in the Management of Tumor Lysis Syndrome in Adults,” Pharmacother, 2006, 26(6):806-12.
Reeves DJ and Bestul DJ, “Evaluation of a Single Fixed Dose of Rasburicase 7.5 mg for the Treatment of Hyperuricemia in Adults With Cancer,” Pharmacother, 2008; 28(6):685–90.
Trifilio S, Gordon L, Singhall S, et al, “Reduced Dose Rasburicase (Recombinant Xanthine Oxidase) in Adult Cancer Patients With Hyperuricemia,” Bone Marrow Transplant, 2006, 37(11):997-1001.
International Brand Names
Lexi-Comp.com
Last full review/revision November 2011
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