Hypersensitivity is an immunologic response5
Hypersensitivity reactions are mediated by the immune system5
- An antigen, such as asparaginase, may trigger an immune response, which results in the proliferation of antibody-producing plasma cells5
- Antibodies may directly bind to the surface of the mast cell, thereby activating the mast cell5
- Upon re-exposure, the antigen may bind to5,9,10:
- Antibodies that are present on the surface of the mast cell (characterized by an IgE response or Type 1 reaction)
- Free antibodies (typically IgG or IgM), which may neutralize or clear the antigen
- Antigens bound to antibodies on mast cells trigger the release of histamine and other mediators that can cause clinical symptoms5
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.