Trade Names:Elspar- Powder for injection, lyophilized 10,000 unitsKidrolase (Canada)
Asparaginase contains the enzyme L-asparagine amidohydrolase. In a significant number of patients with acute leukemia, the malignant cells depend on exogenous asparagine for survival. Administration of asparaginase hydrolyzes serum asparagine to nonfunctional aspartic acid and ammonia, depriving tumor cells of a required amino acid. Tumor cell proliferation is blocked.
T max is 14 to 24 h.
Vd is approximately 70% to 80% of the estimated plasma volume.
Trace amounts found in urine.IV
T ½ is 8 to 30 h.IM
T ½ is 39 to 49 h.
Combination therapy for acute lymphocytic leukemia (ALL). Do not use as the sole induction agent unless combination therapy is deemed inappropriate.Children
ALL. Do not use as the sole induction agent unless combination therapy is deemed inappropriate.
Anaphylactic reactions to asparaginase; pancreatitis or a history of pancreatitis.
IV Give over 30 min through the side arm of an already running infusion of sodium chloride injection or dextrose 5% injection. The drug has little tendency to cause phlebitis when given IV.Children
IM Limit the volume at a single injection site to 2 mL. For a volume greater than 2 mL, use 2 injection sites.ALL Induction RegimensChildren
One of the following combination regimens is recommended for ALL in children.ALL Induction Regimen IChildren Prednisone
40 mg/m 2 /day PO in 3 divided doses for 15 days, followed by tapering of the dosage as follows: 20 mg/m 2 for 2 days, 10 mg/m 2 for 2 days, 5 mg/m 2 for 2 days, 2.5 mg/m 2 for 2 days, and then discontinue.Vincristine sulfate
2 mg/m 2 IV once weekly on days 1, 8, and 15. The maximum single dose should not exceed 2 mg.Asparaginase
1,000 units/kg/day IV for 10 successive days beginning on day 22. When remission is obtained, institute appropriate maintenance therapy. Do not use asparaginase as part of a maintenance regimen. Asparaginase has been used in other combination regimens. Administering the drug IV concurrently with or immediately before a course of vincristine and prednisone may be associated with increased toxicity.ALL Regimen IIChildren Prednisone
40 mg/m 2 /day PO in 3 divided doses for 28 days (the total daily dose to the nearest 2.5 mg), then gradual discontinuation over 14 days.Vincristine sulfate
1.5 mg/m 2 IV weekly for 4 doses, on days 1, 8, 15, and 22. The maximum single dose should not exceed 2 mg.Asparaginase
6,000 units/m 2 IM on days 4, 7, 10, 13, 16, 19, 22, 25, and 28. When remission is obtained, institute appropriate maintenance therapy. Do not use asparaginase as part of a maintenance regimenALL Single Agent Induction TherapyAdults/Children
IV Use asparaginase as the sole induction agent only when a combined regimen is inappropriate because of toxicity or other specific patient-related factors, or in cases refractory to other therapy. Administer 200 units/kg/day IV for 28 days. Complete remissions are of short duration, 1 to 3 mo.
Store at 2° to 8°C (36° to 46°F). Store reconstituted solution at 2° to 8°C (36° to 46°F); discard after 8 h or sooner if cloudy.
Asparaginase may diminish or abolish methotrexate's effect on malignant cells. Do not use methotrexate with, or following asparaginase, while asparagine levels are below normal. Asparaginase may augment corticosteroid-induced hyperglycemia.Vincristine and prednisone
IV administration may be associated with increased toxicity.
May interfere with the interpretation of thyroid function tests by producing a rapid and marked reduction in serum concentrations of thyroxine-binding globulin within 2 days after the first dose.
Depression; confusion; hallucinations; headache; Parkinson-like syndrome.
Moderate potential for nausea, vomiting. Pancreatitis, sometimes fulminant, and acute hemorrhagic pancreatitis have occurred, both may be fatal; fatty changes in the liver; elevation of LFTs.
Hypofibrinogenemia; decreased synthesis of clotting factors and antithrombin III.
Acute anaphylactoid reactions are common; discontinuation of therapy and administration of fluids, corticosteroids, antihistamines, or pressors may be required.
Azotemia, usually prerenal; transient proteinuria.
Chills; fever; weight loss (usually mild); fatal hyperthermia; hypoglycemia.
Be prepared to treat anaphylaxis at each administration.
Intradermal skin test should be performed prior to initial administration of this drug and repeated when at least 1 wk separates doses.
Monitor leukocyte counts and serum uric acid. Take appropriate preventive measures. Monitor peripheral blood count and bone marrow frequently.Serum amylase
Obtain frequent serum amylase to detect early evidence of pancreatitis. If pancreatitis occurs, discontinue therapy.
Category C .
Discontinue breast-feeding or the drug.
Toxicity is reported to be greater in adults than in children.
Patients who have received a course of therapy, if treated again, have an increased risk of hypersensitivity reactions. Therefore, repeat treatment only when the benefit of such therapy is weighed against the increased risk.
Bone marrow depression, leukopenia, thrombosis, and clotting factors depressed; increase in blood ammonia during the conversion of asparagine to aspartic acid by the enzyme.
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