Asparaginases

Asparaginases

Asparaginases are cell cycle’specific and act during the G1 phase. They include:

• asparaginase
• pegaspargase.

Pharmacokinetics

Asparaginase is administered parenterally. It’s considered 100% bioavailable when administered I.V. and about 50% bioavailable when administered I.M.

Distribution and metabolism

After administration, asparaginase remains inside the blood vessels, with minimal distribution elsewhere. The metabolism of asparaginase is unknown; only trace amounts appear in urine.

Pharmacodynamics

Asparaginase and pegaspargase capitalize on the biochemical differences between normal cells and tumor cells.

Tumor cells’eat your asparagine or else

Most normal cells can synthesize asparagine, but some tumor cells depend on other sources of asparagine for survival. Asparaginase and pegaspargase help to degrade asparagine to aspartic acid and ammonia. Deprived of their supply of asparagine, the tumor cells die.

Pharmacotherapeutics

Asparaginase is used primarily in combination with standard chemotherapy to induce remission in patients with acute lymphocytic leukemia.

Warning!

Adverse reactions to asparaginase drugs

Many patients receiving asparaginase and peg-aspargase develop nausea and vomiting. Fever, headache, abdominal pain, pancreatitis, coagulopathy, and liver tox-icity may also occur.

Rising risk

Asparaginase and peg-aspargase can cause anaphylaxis, which is more likely to occur with intermittent I.V. dosing than with daily I.V. dosing or I.M. injections. The risk of a reaction rises with each successive treatment.

Hypersensitivity reactions may also occur.

If allergic…

Pegaspargase is used to treat acute lymphocytic leukemia in patients who are allergic to the native form of asparaginase.

Drug interactions

Asparaginase drugs may interact with other drugs. Asparaginase and pegaspargase may reduce the effectiveness of methotrexate. Concurrent use of asparaginase with prednisone or vincristine increases the risk of toxicity.