Version May 2024
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:
Note: Although weight-directed dosing (mg/kg) with multiple days of therapy is described in the prescribing information and guidelines, (Ref) recent reports have described cost-reducing practice trends using fixed doses, lower maximum doses, and/or fewer doses while maintaining efficacy (Ref); optimal regimen not established.
Fixed dosing:
Note: Various regimens have been reported with doses that are fixed based on rounding to nearest 1.5 mg vial size. Dosing presented is a synthesis of various reported experience; refer to specific protocols.
Infants: Very limited data available: IV: 0.15 to 0.2 mg/kg/dose once; maximum dose: 1.5 mg/dose. Additional doses may be needed once daily based on serum uric acid levels (Ref).
Children and Adolescents: Limited data available:
Weight ≤30 kg: IV: 1.5 mg once. Additional doses may be needed once daily based on serum uric acid levels (Ref).
Weight >30 to ≤60 kg: IV: 1.5 mg, 3 mg, or 6 mg once. Additional doses may be needed once daily based on serum uric acid levels (Ref).
Weight >60 to ≤90 kg: IV: 3 mg, 4.5 mg, or 6 mg once. Additional doses may be needed once daily based on serum uric acid levels (Ref).
Weight >90 kg: IV: 6 mg once. Additional doses may be needed once daily based on serum uric acid levels (Ref).
Dosing based on various types of study design. The largest report (n=105 for age <18 years, n=81 for >18 years) utilized a weight-based dose of 0.15 mg/kg with a lower maximum dose of 1.5 mg for all patients; based on this dosing all patients ≥10 kg would receive the 1.5 mg dose (Philips 2018). In another report, a set 1.5 mg fixed dose in all patients (n=18, age range: 8 months to 14 years) regardless of weight was used; when the fixed 1.5 mg dose was broken down to weight-based for subjects included, the mean dose was 0.085 mg/kg and the heaviest patient (age 13 years) received 0.04 mg/kg/dose (Ref). Another trial included 24 pediatric patients (and 31 adults) and utilized a lower dose of 0.05 mg/kg, which was then rounded to the nearest vial size so patients received a fixed dose of 1.5 mg, 3 mg, or 6 mg (Ref). Another report described 48 patients ≥30 kg receiving a fixed dose of 6 mg (Ref).
Weight-directed dosing:
Infants, Children, and Adolescents: IV: 0.05 to 0.2 mg/kg/dose once daily for 1 to 7 days (average: 2 to 3 days; manufacturer's labeling: up to 5 days) (Ref); 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.
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: 0.1 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) (Ref):
High risk: IV: 0.2 mg/kg once daily (duration is based on plasma uric acid levels).
Intermediate risk: IV: 0.15 mg/kg once daily (duration is based on plasma uric acid levels).
Low risk: IV: 0.1 mg/kg once daily (duration is based on clinical judgment).
Single-dose rasburicase (off-label dosing): IV: 0.15 mg/kg (Ref) or 3 to 7.5 mg as a single dose (Ref); 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 (Ref). 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 (Ref).
Prevention in high-risk patients with hematologic malignancies (off-label dosing): IV: 3 mg as a single dose (Ref).
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).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (minimal excretion by the kidney) (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (large molecular weight): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (large molecular weight): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; however, baseline liver enzymes did not impact rasburicase pharmacokinetics.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in infants, children, adolescents, and adults unless otherwise indicated.
>10%:
Cardiovascular: Peripheral edema (adults: 50%)
Dermatologic: Skin rash (13%; serious: <1%)
Endocrine & metabolic: Hypervolemia (adults: 12%), hypophosphatemia (adults: 17%)
Gastrointestinal: Abdominal pain (20% to 22%), constipation (20%), diarrhea (20%), nausea (27% to 58%), stomatitis (15%), vomiting (38% to 50%)
Hepatic: Hyperbilirubinemia (16%), increased serum alanine aminotransferase (adults: 11%)
Immunologic: Antibody development (infants, children, and adolescents: 11%; adults [IgE]: 6%), development of IgG antibodies (adults: 18%; neutralizing 8%)
Infection: Sepsis (adults: 12%)
Nervous system: Anxiety (adults: 24%), headache (26%)
Respiratory: Pharyngolaryngeal pain (adults: 14%)
Miscellaneous: Fever (46%)
1% to 10%:
Endocrine & metabolic: Hyperphosphatemia (adults: 10%)
Hypersensitivity: Hypersensitivity reaction (adults: 4%)
<1%:
Hematologic & oncologic: Hemolysis, methemoglobinemia
Hypersensitivity: Anaphylaxis
Frequency not defined:
Cardiovascular: Ischemic heart disease, supraventricular cardiac arrhythmia
Gastrointestinal: Gastrointestinal infection
Respiratory: Pulmonary hemorrhage, respiratory failure
Postmarketing:
Nervous system: Seizure
Neuromuscular & skeletal: Muscle spasm
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: Rasburicase may cause hemolysis (<1%). Severe hemolytic reactions occurred within 2 to 4 days of rasburicase initiation. Screen patients at higher risk for G6PD deficiency (eg, patients of African or Mediterranean descent) prior to therapy.
• Hypersensitivity: Serious and fatal hypersensitivity reactions (including anaphylaxis) have been reported. 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: Methemoglobinemia has been reported (<1%), including cases of serious hypoxemia requiring medical intervention. 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: 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).
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
Solution (reconstituted) (Elitek Intravenous)
1.5 mg (per each): $1,289.42
7.5 mg (per each): $6,447.08
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 (Ref); 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. Infuse through a separate line or flush IV line 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 (Ref); 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).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Outcome data related to the use of rasburicase in pregnancy are limited (Middeke 2014).
Plasma uric acid levels (every 6 to 8 hours until tumor lysis syndrome 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/ethnicity: The geometric mean values of body weight-normalized clearance were approximately 40% lower in Japanese patients than in White patients.
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