asparaginase

n.
An enzyme isolated from bacteria that catalyzes the hydrolysis of asparagine and is used in the chemotherapeutic treatment of leukemia.

Key Terms: Acute lymphocytic leukemia, Anaphylaxis.

Definition

Asparaginase (also known as L-asparaginase, and sold under the brand name Elspar) is a medicine used to stop growth of cancer and formation of new cancer cells.

Purpose

Asparaginase is used as part of an induction regimen for the treatment of acute lymphocytic leukemia (ALL) in children.

Description

Asparaginase is an enzyme made from the bacteria escherichia coli (E. coli). In this country, two forms of asparaginase are available: one made from E. coli, and a slightly changed version of the E.Coli form linked to polyethylene glycol (PEG) molecule. This PEG-linked asparaginase is called pegaspargase. This version was made available in 1994, is more expensive than the other form, and is mainly used in patients who have developed an allergy to E. Coli. Another natural form of asparaginase made from the plant bacteria erwinia carotovora is known by the brand name Erwinar and can be specially obtained for patients who develop a severe allergy to E. coli asparaginase. Asparaginase kills cancer cells by depleting a certain protein in the blood (L-asparagine) that is necessary for survival and growth of tumor cells in patients with ALL. Fortunately, normal cells are not dependent on L-asparagine for survival.

Asparaginase is mainly given in combination with vincristine and steroids (either prednisone or dexamethasone) for the first three weeks of therapy.

Recommended Dosage

Adults and Children

Induction Chemotherapy for All

Doses vary between different chemotherapy protocols. The usual dose is 6,000-10,000 units per square meter of body surface area given for 10 days. Patients should refer to individual protocol for recommended dose.

Administration

This medicine can be given directly into the muscle (intramuscular) or into the vein (intravenous). Intramuscular injection of asparaginase lowers the risk of severe allergic reactions (also known as hypersensitivity or anaphylaxis). The risk of hypersensitivity reaction is higher with the second and third dose of the drug.

Precautions

The use of this medication should be avoided in patients with active pancreatitis (inflammation of the pancreas) or history of pancreatitis, and in patients with serious allergic reaction to asparaginase in the past.

Asparaginase should only be given in a hospital. A patient's blood pressure will need to be monitored every 15 minutes for the first hour. A small test dose may be given to check if patient is allergic to this medicine.

This medication can lower the body's ability to fight infections. Patients should avoid contact with crowds or any individual that may have an infection.

Breast-feeding mothers should use asparaginase with caution. It is not yet known whether this drug crosses into breast milk. Women who are pregnant or may become pregnant should avoid this drug unless the benefits to the mother outweigh the risks to the child.

Contact a doctor immediately if any of these symptoms develop:

• fever, chills, sore throat
• yellowing of the skin or eyes
• puffy face, skin rash, trouble breathing, joint pain
• drowsiness, confusion, hallucinations, convulsions
• unusual bleeding or bruising
• stomach pain with nausea, vomiting and loss of appetite

A physician will perform blood tests before starting therapy and during therapy to monitor complete blood count, blood sugar, and pancreas, kidney, and liver functions.

Side Effects

Asparaginase is a very potent medicine that can cause serious side effects. An allergic reaction with skin rash, itching, joint pain, puffy face, and difficulty breathing can occur very quickly after injection with his drug. This side effect is managed by having the drugs epinephrine, diphenhydramine, and steroids available near the bedside to counter the allergic reaction if it occurs. Other common side effects include nausea, vomiting, diarrhea, loss of appetite, stomach cramps, and yellowing of the eyes or skin. Less frequent side effects include high blood sugar, drowsiness, confusion, hallucinations, convulsions, decreased kidney function, increased blood clotting, mouth sores, and decreased ability to fight infections. Usually the side effects of asparaginase are more severe in adults than in children.

Interactions

Asparaginase can decrease effectiveness of methotrexate in killing cancer cells when given right before and together with methotrexate. The use of these two medicines together should be avoided.

Asparaginase can decrease breakdown and increase toxicity of cyclophosphamide.

Risk of liver disease may be increased in patients receiving both asparaginase and mercaptopurine.

This medicine can increase blood sugar especially when given in together with steroids.

Asparaginase should be given after vincristine instead of before or with vincristine because it can increase the risk of numbing, tingling and pain in hands and feet.

—Olga Bessmertny, Pharm.D.

An enzyme that catalyzes the deamination of asparagine; used as an antineoplastic agent against cancers, e.g. acute lymphocytic leukemia, in which the malignant cells require exogenous asparagine for protein synthesis.

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