Asparaginase

Synonyms :

L-Asparaginase, L-Asparginase

Mechanism :

Asparaginase contains the enzyme L-asparagine amidohydrolase, derived from Escherichia coli. In a significant number of patients with acute leukemia, particularly lymphocytic, the malignant cells are dependent on an exogenous source of asparagine for survival. Normal cells, however, can synthesize asparagine and thus are less affected by the rapid depletion produced by treatment with the enzyme asparaginase.

Indication :

Acute lymphoblastic leukemia
Acute myeloid leukemia
Non-Hodgkin lymphoma

Contraindications :

Contraindicated in patients with pancreatitis or a history of pancreatitis, and known hypersensitivity to it.

Dosing :

Always consult the current treatment protocol for details of dosage and scheduling. Perform intradermal sensitivity testing with 2 units of asparginase before the initial dose and when a week or more has elapsed between doses.

As part of combination therapy-IM:

6000 units/m², 3 times/week for 3 weeks.

High-dose IM therapy:

25,000 units/m²/dose weekly once for 9 doses.

IV therapy:

1000 units/kg/24 hours for 10 days.

Single drug therapy:

200 IU/kg/24 hours for 28 days.

Adverse Effect :

Allergic reactions (skin rashes, urticaria, arthralgia, respiratory distress, and acute anaphylaxis), fatal hyperthermia, depression, somnolence, fatigue, coma, confusion, agitation, hallucinations, nausea, vomiting, acute pancreatitis, elevations of AST/ALT, alkaline phosphatase, bilirubin, hypoalbuminemia, hypercholesterolemia, increased plasma fibrinogen, azotemia, proteinuria. Bone marrow suppression: Onset 7 days, nadir 14 days, recovery 21 days.

Interaction :

It should not be mixed with any other drug before administration.

Hepatic Dose :

Mild to moderate hepatic impairment: No dosage adjustments are recommended.
Severe hepatic impairment: Use is contraindicated

Hepatotoxicity during therapy:
Direct bilirubin <3 mg/dL: Continue therapy.
Direct bilirubin >3 to 5 times upper limit of normal (ULN): Withold therapy until total bilirubin decreases to =2 ULN. May switch to other asparginase product. Direct bilirubin >5 mg/dL: Discontinue asparaginase.
ALT/AST >3 to 5 times ULN: Continue therapy.
ALT/AST >5 to 20 times ULN: Delay next dose until transaminases <3 times ULN.
ALT/AST >20 times ULN: Discontinue therapy if it takes longer than 1 week for transaminases to return to <3 times ULN.
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