The role of asparagine in ALL2,3
Leukemic cells need asparagine to survive and proliferate2,3
The amino acid asparagine is essential for the survival and reproduction of leukemic cells2,3
- Although most normal cells can synthesize asparagine, leukemic cells rely on extracellular sources
- Leukemic cells are thought to be unable to synthesize asparagine due to the lack of asparagine synthetase activity
Asparaginase proposed mechanism of action2-4
Asparaginase is believed to deprive leukemic cells of asparagine2-4
- Asparaginase converts serum asparagine into aspartic acid and ammonia2,3
- Since asparagine is an essential amino acid that leukemic cells cannot synthesize, its depletion is thought to result in the death of leukemic cells2-4
ERWINAZE® (asparaginase Erwinia chrysanthemi) for intramuscular injection (IM) or intravenous infusion (IV), 10,000 International Units (IU)/vial, is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase.
IMPORTANT SAFETY INFORMATION
ERWINAZE is contraindicated in patients with a history of:
- Serious hypersensitivity reactions to ERWINAZE, including anaphylaxis
- Serious pancreatitis with prior L-asparaginase therapy
- Serious thrombosis with prior L-asparaginase therapy
- Serious hemorrhagic events with prior L-asparaginase therapy
Warnings and Precautions
After the use of ERWINAZE in clinical trials, grade 3 and 4 hypersensitivity reactions have occurred in 5% of patients. Administer in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis. If a serious hypersensitivity reaction occurs (including anaphylaxis), discontinue ERWINAZE and initiate appropriate therapy.
In clinical trials, 4% of patients reported pancreatitis with ERWINAZE therapy. Discontinue ERWINAZE for severe or hemorrhagic pancreatitis manifested by abdominal pain >72 hours and amylase elevation ≥2.0 x ULN. In case of mild pancreatitis, hold ERWINAZE until the signs and symptoms subside and amylase levels return to normal. After resolution, ERWINAZE therapy may be resumed.
In clinical trials, 5% of patients reported glucose intolerance, which in some cases may be irreversible. Monitor glucose levels at baseline and periodically during treatment. Administer insulin therapy as necessary in patients with hyperglycemia.
Thrombosis and Hemorrhage
Serious thrombotic events, including sagittal sinus thrombosis, have been reported in both E. coli and Erwinia-derived L-asparaginase therapy. The following coagulation proteins were decreased in the majority of patients after a 2-week course of ERWINAZE by intramuscular administration: fibrinogen, protein C activity, protein S activity, and anti-thrombin III. Discontinue ERWINAZE for a thrombotic or hemorrhagic event until symptoms resolve; after resolution, ERWINAZE therapy may be resumed.
Most Common Adverse Reactions
The most common adverse reactions (incidence 1% or greater) with ERWINAZE treatment are systemic hypersensitivity, hyperglycemia, transaminases abnormal, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain/discomfort, and diarrhea.
Use in Specific Populations
Pregnancy and Lactation
ERWINAZE can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Females of reproductive potential should be advised to use effective contraception during treatment with ERWINAZE and for 3 months after the final dose. Since an indirect interaction between oral contraceptives and ERWINAZE cannot be ruled out, a method of contraception other than oral contraceptives should be used. Breastfeeding is not recommended during treatment with ERWINAZE and for 3 months after the last dose.
Please see full Prescribing Information.