asparaginase (as-PAYR-uh-jih-NAYS) is a drug that is used to treat acute lymphoblastic leukemia (ALL) and is being studied in the treatment of some other types of cancer. It is an enzyme taken from the bacterium Escherichia coli (E. coli) . It breaks down the amino acid asparagine and may block the growth of tumor cells that need asparagine to grow. Also called Elspar and L-asparaginase.
Information about Asparaginase
Liver safety of Asparaginase
L-asparaginase has many side effects, one of which is hepatic injury that is characterized by inhibition of hepatic protein synthesis and steatosis, which can be severe and lead to death from hepatic failure.
Mechanism of action of Asparaginase
Asparaginase (as par' a jin ase), often referred to as L-asparaginase, is a bacterial enzyme that acts to decrease tissue stores of asparagine, a secondary amino acid that is important in the growth of many cancers. Asparaginase, prepared from E. coli, was introduced into cancer chemotherapy over 50 years ago and remains an important agent in the therapy of acute lymphocytic leukemia. Asparaginase has activity against other cancer types, but is rarely used for other indications.
FDA approval information for Asparaginase
Asparaginase was first approved for use in the United States in 1972 as an anticancer agent, with initial preparations being prepared from E. coli. Pegylated formulations of E. coli-derived asparaginase (pegaspargase) became available and were approved for use in 1994. These preparations can be given every other week and have largely replaced standard asparaginase. Asparaginase made from other bacteria (Erwinia chrysanthemi) was approved for use in the United States in 2011 and is available under the brand name Erwinaze.
Dosage and administration for Asparaginase
Standard asparaginase is given either by intramuscular injection or, more typically, intravenous injection in doses of 25,000 IU/m2 three times weekly in 14 day cycles. Pegaspargase can also be given intramuscularly or intravenously, typically in a dose of 2500 IU/m2 every other week. Both standard and pegylated asparaginase are usually given in combination with other antineoplastic agents such as vincristine, mercaptopurine, methotrexate, daunorubicin, and prednisone.
Side effects of Asparaginase
Asparaginase has many dose related toxicities including nausea, fever, hypersensitivity reactions (urticaria, wheezing), clotting abnormalities, bone marrow suppression, pancreatitis, hepatotoxicity and central nervous system toxicities.
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