Asparaginase


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Asparaginase
Asparaginase (Elspar)
Asparaginase
(ah- SPAIR-ah-jin-ays)
Pregnancy Category: C Colaspase Elspar Kidrolase (Abbreviation: Lcf-ASP) (Rx)

Classification: Antineoplastic, miscellaneous

See Also: See also Antineoplastic Agents.

Action/Kinetics: Asparaginase, derived from Escherichia coli contains the enzyme L-asparagine amidohydrolase, type EC-2 . Neoplastic cells are unable to synthesize sufficient asparagine, an amino acid, to meet their metabolic needs. The supply of asparagine is further decreased by the enzyme asparaginase, which breaks down asparagine to aspartic acid and ammonia. Asparaginase interferes with synthesis of DNA, RNA, and protein and is cell-cycle specific for the G 1 phase of cell division. Time to peak plasma levels, after IM: 14-24 hr. t 1/2, after IV: 8-30 hr; after IM: 39-49 hr. Accumulates in plasma and tissue, and a small amount (1%) appears in CSF. Excretion is unknown. More toxic in adults than in children.

Uses: Acute lymphocytic leukemia in children; mostly used in combination with other drugs. Not to be used for maintenance therapy. Investigational: Acute myelocytic and myelomonocytic leukemia, chronic lymphocytic leukemia, Hodgkin's and non-Hodgkin's lymphomas, melanosarcoma.

Contraindications: Anaphylactic reactions to asparaginase. Pancreatitis or a history of pancreatitis. Lactation.

Special Concerns: Use with caution in presence of liver dysfunction. Due to the possibility of an increased risk of hypersensitivity, institute retreatment with great care.

Side Effects: GI: N&V, anorexia, abdominal cramps, pancreatitis (sometimes fulminant), acute hemorrhagic pancreatitis. CNS: Depression, somnolence, coma, confusion, fatigue, agitation, mild to severe hallucinations, headache, irritability, Parkinson-like syndrome with tremor and a progressive increase in muscle tone (rare). Hematologic: Marked leukopenia, bone marrow depression (rare). Depression of clotting factors; rarely, intracranial hemorrhage and fatal bleeding. Hypersensitivity: Skin rashes, urticaria, arthralgia, respiratory distress, acute anaphylaxis. Renal: Azotemia, proteinuria (rare), acute renal shutdown, fatal renal insufficiency. Hepatic: Hepatotoxicity, fatty changes in the liver. Miscellaneous: Hyperglycemia with glucosuria and polyuria. Marked hypoalbuminemia associated with peripheral edema, malabsorption syndrome, fatal hyperthermia chills, fever, mild weight loss.

Laboratory Test Alterations: Blood ammonia, BUN, glucose, uric acid, AST, ALT, alkaline phosphatase, bilirubin (direct and indirect). Serum albumin, cholesterol (total and esters), plasma fibrinogen. or Decreases in total lipids. Interference with interpretation of thyroid function tests.

Drug Interactions: Methotrexate / Asparaginase effect of methotrexate Prednisone / Even though used with asparaginase, may cause toxicity Vincristine / Even though used with asparaginase, may cause toxicity; hyperglycemic effect

How Supplied: Powder for injection: 10,000 IU

Dosage
?IV, IM When used as the sole agent for induction.
Adults and children: 200 IU/kg/day IV for 28 days.
Regimen I for acute lymphocytic leukemia in children.
Prednisone: 40 mg/m 2/day PO in three divided doses for 15 days, followed by tapering of dosage as follows: 20 mg/m 2/day for 2 days, 10 mg/m 2/day for 2 days, 5 mg/m 2/day for 2 days, 2.5 mg/m 2/day 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 IU/kg/day IV for 10 successive days beginning on day 22.
Regimen II for acute lymphocytic leukemia in children.
Prednisone: 40 mg/m 2/day PO in three divided doses for 28 days with the total daily dose to the nearest 2.5 mg; then, discontinue gradually over 14 days. Vincristine sulfate: 1.5 mg/m 2 IV weekly for four doses on days 1, 8, 15, and 22. The maximum single dose should not exceed 2 mg. Asparaginase: 6,000 IU/m 2 IM on days 4, 7, 10, 13, 16, 19, 22, 25, and 28. When remission is obtained with either regimen, appropriate maintenance therapy should be instituted. Asparaginase should not be used for maintenance therapy.

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