Rasburicase may cause serious and fatal hypersensitivity reactions, including anaphylaxis. Immediately and permanently discontinue rasburicase in patients who experience a serious hypersensitivity reaction.
Do not administer rasburicase to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Immediately and permanently discontinue rasburicase in patients developing hemolysis. Screen patients at higher risk for G6PD deficiency (eg, patients of African or Mediterranean ancestry) prior to starting rasburicase.
Rasburicase can result in methemoglobinemia in some patients. Immediately and permanently discontinue rasburicase in patients developing methemoglobinemia.
Rasburicase 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.
Hyperuricemia associated with malignancy: Infants, Children, and Adolescents:
Multiple-dosing:
Manufacturer's labeling (Elitek): IV: 0.2 mg/kg/dose once daily for up to 5 days
Alternate dosing (Coiffier 2008): Limited data available: IV: 0.05 to 0.2 mg/kg/dose once daily for 1 to 7 days (average: 2 to 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 and baseline uric acid level >7.5 mg/dL: 0.2 mg/kg/dose once daily (duration is based on plasma uric acid levels)
Intermediate risk and baseline uric acid level <7.5 mg/dL: 0.15 mg/kg/dose once daily (duration is based on plasma uric acid levels); may consider managing initially with a single dose
Low risk and baseline uric acid level <7.5 mg/dL: 0.1 mg/kg/dose once daily (duration is based on clinical judgment); a dose of 0.05 mg/kg was used (with good results) in one trial
Single-dose: Limited data available: IV: 0.15 mg/kg/dose; additional doses may be needed based on serum uric acid levels (Liu 2005)
Prevention in high-risk patients with hematologic malignancies: IV: 0.2 mg/kg/dose as a single dose (Jones 2015)
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Rasburicase: Drug information")
Hyperuricemia associated with malignancy: IV: 0.05 to 0.2 mg/kg once daily for 1 to 7 days (average of 2 to 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) (Coiffier 2008):
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 (off-label dosing): 0.15 mg/kg (Campara 2009; Liu 2005) or 3 to 7.5 mg as a single dose (Hutcherson 2006; McBride 2013; McDonnell 2006; Reeves 2008; Trifilio 2006); repeat doses (1.5 to 6 mg) may be needed based on serum uric acid levels. A meta-analysis of 10 studies determined that the pooled response rate of single-dose rasburicase (doses ranging from 0.05 mg/kg to 0.2 mg/kg) was not inferior to daily rasburicase dosing while allowing for cost savings; monitor closely in case an additional dose may be needed (Feng 2013). Another meta-analysis of 15 studies determined that a single 6 mg dose was sufficient to lower and maintain uric acid and creatinine levels in adult patients with TLS; if the uric acid level is <12 mg/dL, single doses of 3 mg or 4.5 mg may be considered with close monitoring and if needed, repeat doses (Yu 2017).
Prevention in high-risk patients with hematologic malignancies (off-label dosing): IV: 3 mg as a single dose (Jones 2015)
Manufacturer’s labeling: IV: 0.2 mg/kg once daily for up to 5 days (use beyond 5 days or administration of more than 1 course is not recommended)
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Elitek: 1.5 mg (1 ea); 7.5 mg (1 ea)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Fasturtec: 1.5 mg (1 ea)
IV: Infuse over 30 minutes; do not administer as a bolus infusion. During administration, do not filter or mix with other medications. If not possible to administer through a separate line, IV line should be flushed with at least 15 mL NS prior to and following rasburicase infusion. The optimal timing of rasburicase administration (with respect to chemotherapy administration) is not specified in the manufacturer's 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.
IV: IV infusion over 30 minutes; do not administer as a bolus. 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 manufacturer's 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.
The lyophilized drug product and the diluent for reconstitution should be stored at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Reconstituted solution and solution diluted for infusion may be stored for up to 24 hours at 2°C to 8°C (36°F to 46°F). Discard unused product.
Initial management of plasma uric acid levels in 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 (FDA approved in ages ≥1 month and adults)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (50%)
Central nervous system: Headache (26%), anxiety (24%)
Dermatologic: Rash (13%; serious: <1%)
Endocrine & metabolic: Hypophosphatemia (17%), hypervolemia (12%)
Gastrointestinal: Nausea (27% to 58%), vomiting (38% to 50%), abdominal pain (20% to 22%), constipation (20%), diarrhea (20%), mucositis (15%)
Hepatic: Hyperbilirubinemia (16%), increased serum ALT (11%)
Immunologic: Antibody development (children: 11%; IgE: 6%), development of IgG antibodies (18%; neutralizing 8%)
Infection: Sepsis (12%; serious: 5%)
Respiratory: Pharyngolaryngeal pain (14%)
Miscellaneous: Fever (46%)
1% to 10%:
Cardiovascular: Ischemic heart disease (≥2%), supraventricular arrhythmia (≥2%)
Endocrine & metabolic: Hyperphosphatemia (10%)
Gastrointestinal: Gastrointestinal infection (≥2%)
Hematologic & oncologic: Pulmonary hemorrhage (≥2%)
Hypersensitivity: Hypersensitivity (4%)
Infection: Infection (abdominal, ≥2%)
Respiratory: Respiratory failure (≥2%)
<1%, postmarketing, and/or case reports: Anaphylaxis, hemolysis, methemoglobinemia, muscle spasm, seizure
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
Concerns related to adverse effects:
• Hemolysis: [US 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 or Mediterranean descent) should be screened prior to therapy. Severe hemolytic reactions occurred within 2 to 4 days of rasburicase initiation.
• Hypersensitivity: [US Boxed Warning]: Serious and fatal hypersensitivity reactions (including anaphylaxis) have been reported; immediately and permanently discontinue in patients developing a 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. The safety and efficacy of more than one course of administration has not been established.
• Methemoglobinemia: [US 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 IV 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; efficacy may be reduced with subsequent courses of therapy.
• Uric acid degradation: [US 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 (sample should remain on ice until analyzed).
Data suggest that children <2 years of age may experience a higher frequency of adverse effects than adults, particularly vomiting (75% vs 55%), diarrhea (63% vs 20%), fever (50% vs 38%), and rash (38% vs 10%).
None known.
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Based on data from animal reproduction studies, in utero exposure to rasburicase may cause fetal harm. Information related to the use of rasburicase in pregnancy is limited (Middeke 2014).
Plasma uric acid levels (4 hours after rasburicase administration, then every 6 to 8 hours until TLS resolution), electrolytes, hydration status, CBC, G6PD deficiency screening (in patients at high risk for deficiency); monitor for hypersensitivity
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.
Onset: Uric acid levels decrease within 4 hours of initial administration
Distribution: Pediatric patients: 110 to 127 mL/kg; Adults: 76 to 138 mL/kg
Half-life elimination: ~16 to 23 hours
Race: The geometric mean values of body weight-normalized clearance were approximately 40% lower in Japanese patients than in white patients.
Solution (reconstituted) (Elitek Intravenous)
1.5 mg (per each): $1,182.98
7.5 mg (per each): $5,914.86
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