Rasburicase catalyzes the enzymatic oxidation of uric acid to the inactive and more soluble metabolite, allantoin. It is a recombinant form of urate oxidase produced by cloning the gene for Aspergillus flavus urate oxidase for expression in Saccharomyces cerevisiae. Rasburicase 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 anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid. The uric acid response rate was significantly higher with rasburicase compared with allopurinol (87% vs. 66%; p = 0.001) in adult patients with active leukemia or lymphoma at high risk for hyperuricemia and tumor lysis syndrome in a randomized, 3-arm, phase III trial (n= 275). Treatment with rasburicase resulted in a 2.6-fold reduction in uric acid exposure compared with allopurinol in pediatric patients (age range, 0.3 to 17 years) with leukemia or lymphoma at high risk for tumor lysis in a multicenter, randomized trial (n = 52). Rasburicase was approved by the FDA in 2002 for pediatric patients and in 2009 for adult patients.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Dilution is required prior to administration as an infusion.
-Do not administer as an IV bolus.
Reconstitution of rasburicase vial:
-Use the provided diluent. Add 1 mL of diluent to the 1.5-mg vial or 5 mL of diluent to the 7.5-mg vial for a final concentration of 1.5 mg/mL.
-Do not shake or vortex the vial; gently swirl to mix.
Preparation of infusion:
-Inject the calculated dose of reconstituted rasburicase solution into an infusion bag containing the appropriate volume of 0.9% Sodium Chloride injection, to achieve a final total volume of 50 mL.
-Storage following infusion preparation: Store diluted infusion solution at 2 to 8 degrees C (36 to 46 degrees F); infuse within 24 hours of preparation.
Intravenous infusion:
-Infuse the diluted solution IV over 30 minutes. Do not use filters during the infusion.
-Infuse through a separate line; if the use of a separate line is not possible, flush the line with at least 15 mL of 0.9% Sodium Chloride injection prior to and after each infusion.
Hemolysis and methemoglobinemia have been reported with rasburicase therapy in clinical trials (n = 887); both hemolysis and methemoglobinemia occurred in less than 1% of patients. Some patients with methemoglobinemia experienced serious hypoxemia requiring intervention with medical support measures. Permanently discontinue rasburicase if a patient experiences hemolysis or methemoglobinemia and start appropriate monitoring and medical management (e.g., transfusion support for hemolysis and transfusion support and methylene-blue administration for methemoglobinemia). Severe hemolytic reactions have occurred within 2 to 4 days of starting rasburicase.
Gastrointestinal (GI) toxicity occurred with rasburicase (n = 92) or rasburicase plus allopurinol (combination therapy; n = 92) in adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome in a multicenter, 3-arm, randomized study. GI toxicity included abdominal pain (rasburicase alone: 21.7% (grade 3/4, 3.3%); combination therapy: 33.7% (grade 3/4, 4.3%)), nausea (rasburicase alone: 57.6% (grade 3/4, 1.1%); combination therapy: 60.9% (grade 3/4, 1.1%)), and vomiting (rasburicase alone: 38% (grade 3/4, 1.1%); combination therapy: 37% (grade 3/4, 0%)). Abdominal pain (20%), constipation (20%), diarrhea (20%), mucositis/oral ulceration (15%), nausea (27%), and vomiting (50%) were reported in patients who received rasburicase in a pooled analysis of 4 studies (n = 347; adults, n = 82; pediatric patients, n = 265).
Antibody formation has been reported with rasburicase use. Antibodies developed 28 days after rasburicase administration (ELISA assessment) in 11% of pediatric patients with hematologic malignancies tested in clinical trials (n = 218). In adult patients with hematological malignancies and no prior exposure to rasburicase (n = 260), 18% of patients were positive for anti-rasburicase immunoglobulin G (IgG), 8% of patients were positive for anti-rasburicase neutralizing IgG, and 6% of patients were positive for anti-rasburicase immunoglobulin E at day 14 to 24 months following 5 daily doses of rasburicase.
Fever was reported in 46% of patients who received rasburicase in a pooled analysis of 4 studies (n = 347; adults, n = 82; pediatric patients, n = 265).
In a multicenter, 3-arm, randomized study, anxiety occurred in 23.9% and 17.4% of adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome who received single-agent rasburicase (n = 92) and rasburicase plus allopurinol (n = 92), respectively. Additionally, grade 3 or 4 anxiety was reported in 3.3% of patients who received single-agent rasburicase.
Abdominal infection and GI infection occurred at an incidence that was at least 2% greater in patients who received rasburicase compared with patients who received allopurinol in 2 randomized studies. In a multicenter, 3-arm, randomized study, sepsis occurred in 12% and 7.6% of adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome who received single-agent rasburicase (n = 92) and rasburicase plus allopurinol (n = 92), respectively. Additionally, grade 3 or 4 sepsis was reported in 5.4% and 6.5% of patients, respectively.
Altered serum phosphate levels occurred with rasburicase (n = 92) or rasburicase plus allopurinol (combination therapy; n = 92) in adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome in a multicenter, 3-arm, randomized study. Serum phosphate changes included hypophosphatemia (rasburicase alone: 17.4% (grade 3/4, 4.3%); combination therapy: 22.8% (grade 3/4, 6.5%)) and hyperphosphatemia (rasburicase alone: 9.8%; combination therapy: 15.2%).
Supraventricular tachycardia (SVT)/arrhythmias and ischemic coronary artery disorders each occurred at an incidence that was at least 2% greater in patients who received rasburicase compared with patients who received allopurinol in 2 randomized studies.
In postmarketing surveillance, seizures and involuntary movements/muscle contractions were reported in patients who received rasburicase.
Edema occurred with rasburicase (n = 92) and rasburicase plus allopurinol (combination therapy; n = 92) in adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome in a multicenter, 3-arm, randomized study. Edema included fluid overload (rasburicase alone: 12%; combination therapy: 6.5%) and peripheral edema (rasburicase alone: 50% (grade 3/4, 2.2%); combination therapy: 43.5% (grade 3/4, 3.3%)).
Pulmonary bleeding and respiratory failure each occurred at an incidence that was at least 2% greater in patients who received rasburicase compared with patients who received allopurinol in 2 randomized studies. In a multicenter, 3-arm, randomized study, pharyngolaryngeal pain occurred in 14.1% and 20.7% of adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome who received single-agent rasburicase (n = 92) and rasburicase plus allopurinol (n = 92), respectively. Additionally, grade 3 or 4 pharyngolaryngeal pain was reported in 1.1% of patients who received single-agent rasburicase.
Elevated hepatic enzymes occurred with rasburicase (n = 92) or rasburicase plus allopurinol (combination therapy; n = 92) in adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome in a multicenter, 3-arm, randomized study. These altered liver function tests included increased ALT levels (rasburicase alone: 10.9% (grade 3/4, 3.3%); combination therapy: 27.2% (grade 3/4, 4.3%)) and hyperbilirubinemia (rasburicase alone: 16.3% (grade 3/4, 3.3%); combination therapy: 14.1% (grade 3/4, 2.2%)).
Headache was reported in 26% of patients who received rasburicase in a pooled analysis of 4 studies (n = 347; adults, n = 82; pediatric patients, n = 265).
Rash (unspecified) was reported in 13% of patients who received rasburicase in a pooled analysis of 4 studies (n = 347; adults, n = 82; pediatric patients, n = 265).
Serious hypersensitivity reactions or anaphylaxis has been reported with rasburicase use. Anaphylaxis was reported in less than 1% of patients in clinical studies (n = 887); this may occur after the first dose or at any time during treatment. Permanently discontinue rasburicase if a patient experiences signs or symptoms of a severe hypersensitivity reaction such as bronchospasm, chest pain (unspecified)/tightness, dyspnea, hypoxia, hypotension, anaphylactic shock, and urticaria. In a multicenter, 3-arm, randomized study, hypersensitivity reactions (e.g., arthralgia, injection site reaction/irritation, peripheral edema, and rash) occurred in 4.3% and 1.1% of adult patients with leukemia, lymphoma, or solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome who received single-agent rasburicase (n = 92) and rasburicase plus allopurinol (n = 92), respectively.
Rasburicase causes interference with uric acid measurements by enzymatically degrading uric acid in blood/plasma/serum samples left at room temperature; this results in low plasma uric acid assay readings. To ensure accurate measurements, collect blood into pre-chilled tubes containing heparin and immediately immerse and maintain the tube in an ice water bath. Prepare plasma samples by centrifugation in a pre-cooled centrifuge (4 degrees Celsius). Keep the plasma samples in an ice water bath and analyze within 4 hours of collection.
There is a risk of serious hypersensitivity reactions or anaphylaxis with rasburicase use; fatal anaphylactic reactions have been reported. Rasburicase is contraindicated in patients with a known history of anaphylaxis or hypersensitivity reactions to rasburicase or any component of the product. Permanently discontinue rasburicase if a patient experiences signs or symptoms of a severe hypersensitivity reaction such as acute bronchospasm, chest pain/tightness, dyspnea, hypoxia, hypotension, shock, and urticaria. The rasburicase lyophilized vial contains mannitol; therefore, use caution in patients with a mannitol hypersensitivity. Rasburicase is produced by a genetically modified Saccharomyces cerevisiae (yeast) strain and the DNA coding was cloned from a strain of Aspergillus flavus; use caution in patients with a yeast hypersensitivity.
Rasburicase is contraindicated in patients with a known history of hemolysis or methemoglobinemia with rasburicase and in patients with glucose-6 phosphate dehydrogenase (G6PD) deficiency. Patients who have a high risk of G6PD deficiency, such as patients of African or Mediterranean ancestry, should be screened prior to starting rasburicase. Permanently discontinue rasburicase if a patient experiences hemolysis or methemoglobinemia; start appropriate monitoring and medical management (e.g., transfusion support, methylene blue). It is not known if the risk of methemoglobinemia or hemolytic anemia is increased in patients with deficiencies of cytochrome b5 reductase or of other enzymes with antioxidant activity; use rasburicase with caution in patients with methemoglobin reductase deficiency. Severe hemolytic reactions have occurred within 2 to 4 days of starting rasburicase.
Rasburicase may cause fetal harm if used during pregnancy, based on data from animal studies. Rasburicase use has not been evaluated in pregnant women; weigh the benefits of therapy with the potential risk to the fetus in these patients. Multiple heart and great vessel malformations were observed in the offspring of pregnant rats who received IV rasburicase doses that resulted in 100 times the exposure seen with the recommended human dose. Additionally, decreased fetal body weights and heart and great vessel malformations occurred in the offspring of pregnant rabbits who received IV rasburicase doses that resulted in 5 to 54 times the exposure seen with the recommended human dose.
Advise patients that breast-feeding is not recommended during rasburicase treatment and for 2 weeks after the last dose due to the potential for serious adverse reactions in the breast-fed child. There are no data on the presence of rasburicase in human milk, the effects on the breast-fed child, or the effects on milk production.
For the initial management of plasma uric acid levels in adult and pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and elevation of plasma uric acid:
NOTE: The FDA has designated rasburicase as an orphan drug for the treatment of malignancy-associated or chemotherapy-induced hyperuricemia.
-Weight-based dosing for the initial management of plasma uric acid levels:
Intravenous dosage:
Adults: 0.2 mg/kg IV over 30 minutes once daily for up to 5 days.
Adolescents, Children, and Infants 1 month and older: 0.2 mg/kg IV over 30 minutes once daily for up to 5 days. Patients receive IV hydration (3 L/m2 per day); some patients also receive urinary alkalinization as necessary.
-Fixed-dose therapy*:
Intravenous dosage:
Adults: 3 mg and 6 mg (range, 1.5 to 7.5 mg) IV were the most frequently evaluated fixed doses of rasburicase in retrospective studies; most patients required only 1 fixed dose to achieve normalized uric acid levels. A single, 7.5-mg fixed dose of rasburicase was evaluated in a small, prospective, case-controlled study. Most patients in this study received additional supportive care measures to prevent tumor lysis syndrome such as allopurinol and/or alkalinization.
Maximum Dosage Limits:
-Adults
0.2 mg/kg per day IV for up to 5 days.; fixed-dose*, 7.5 mg IV.
-Geriatric
0.2 mg/kg per day IV for up to 5 days.; fixed-dose*, 7.5 mg IV.
-Adolescents
0.2 mg/kg per day IV for up to 5 days.
-Children
0.2 mg/kg per day IV for up to 5 days.
-Infants
0.2 mg/kg per day IV for up to 5 days.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Articaine; Epinephrine: (Moderate) Coadministration of articaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chloroprocaine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Tetracaine: (Moderate) Coadministration of tetracaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue tetracaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rasburicase catalyzes the enzymatic oxidation of uric acid to the inactive and more soluble metabolite, allantoin. Allantoin is metabolized by peptide hydrolysis and excreted. Rasburicase is a recombinant form of urate oxidase produced by cloning the gene for Aspergillus flavus urate oxidase for expression in Saccharomyces cerevisiae. Humans do not produce urate oxidase due to a nonsense mutation in the coding region of the gene. In some hematologic malignancies and solid tumors, effective anticancer therapy causes a rapid lysis of malignant cells and an abrupt release of cellular contents into the blood resulting in tumor lysis syndrome (TLS). TLS is characterized by hyperuricemia and electrolyte abnormalities (e.g., hyperkalemia, hyperphosphatemia, hypocalcemia) and may lead to acute renal failure, arrhythmias, and/or death. Allopurinol inhibits the xanthine oxidase enzyme and prevents the formation of uric acid. In addition to a unique mechanism of action, rasburicase differs from allopurinol in that it degrades preexisting uric acid, reduces uric acid levels quickly (usually within 4 hours), and does not lead to xanthine accumulation.
Rasburicase is administered as an intravenous infusion. In adult patients with leukemia, lymphoma, or other hematological malignancies, the mean volume of distribution was 75.8 to 138 mL/kg following rasburicase 0.15 to 0.2 mg/kg IV once daily for up to 5 days in a pharmacokinetic analysis. The mean terminal half-life range was 15.7 to 22.5 hours. Additionally, plasma uric acid levels decreased within 4 hours and were maintained below 7.5 mg/dL for at least 7 days in 98% of adult patients. There was no dose response effect on uric acid levels with the 0.2 mg/kg dosage. Rasburicase is metabolized by peptide hydrolysis.
Affected cytochrome P450 isoenzymes: none
Clinically relevant CYP450-mediated drug interactions are not expected in patients who receive the recommended rasburicase dose and dosing schedule. In vivo, rasburicase did not induce or inhibit the activity of CYP1A, CYP2A, CYP2B, CYP2C, CYP2E, or CYP3A.
-Route-Specific Pharmacokinetics
Intravenous Route
The exposure at 24 hours (AUC0-24 hours) and Cmax increased when the rasburicase dose increased from 0.15 to 0.2 mg/kg IV; however, drug accumulation was minimal (less than 1.3 fold) between dosing days 1 and 5.
-Special Populations
Hepatic Impairment
Baseline hepatic function (i.e., liver enzymes) did not significantly affect the pharmacokinetic parameters of rasburicase.
Renal Impairment
Baseline renal function (i.e., creatinine clearance) did not significantly affect the pharmacokinetic parameters of rasburicase.
Pediatrics
In pediatric patients with leukemia, lymphoma, or other hematological malignancies, the mean volume of distribution was 110 to 127 mL/kg following rasburicase 0.15 to 0.2 mg/kg IV once daily for up to 5 days in a pharmacokinetic analysis. The mean terminal half-life range of 15.7 to 22.5 hours was similar in both adult and pediatric patients. Additionally, plasma uric acid levels decreased within 4 hours and were maintained below 7.5 mg/dL for at least 7 days in 90% of pediatric patients. Children less than 2 years of age (n = 24; age 0 to 6 months, n = 7) had higher mean uric acid exposures at 96 hours (150 +/- 16 mg x hour/dL vs. 108 +/- 4 mg x hour/dL) and a lower rate of normal uric acid concentrations by 48 hours (83% vs. 93%) compared with pediatric patients aged 2 to 17 years (n = 222).
Geriatric
Age did not significantly affect the pharmacokinetic parameters of rasburicase.
Gender Differences
Gender did not significantly affect the pharmacokinetic parameters of rasburicase.
Ethnic Differences
The geometric mean values of body-weight normalized rasburicase clearance were about 40% lower in Japanese patients (n = 20) compared with Caucasian patients (n = 22) in a cross-study comparison.