Hypersensitivity reactions to asparaginase may lead to:

  • Shortened asparaginase half-life11
  • Subtherapeutic asparaginase levels and reduced ability to deplete asparagine10,12,13
  • Potential interruptions in asparaginase treatment1,2,4

Impact of hypersensitivity on E. coli asparaginase activity10

Hypersensitivity related to asparaginase activity

Adapted from Zalewska-Szewczyk et al, 2007.

Study Design

In this clinical study, 47 standard- and medium-risk pediatric patients newly diagnosed with ALL received native E. coli asparaginase as part of the treatment protocol for a median of 30 months. Patients received 8 doses of asparaginase (5000 IU/m2) every 3 days during induction and 4 doses (10,000 IU/m2) on 4 specified days in the reinduction phase. Blood samples were collected immediately before the next dose of asparaginase and evaluated for anti-asparaginase antibodies using an enzyme-linked immunosorbent assay (ELISA).10

Note that native E. coli-derived asparaginase is no longer available in the US. However, this information is presented to illustrate the general principles regarding the potential impact of hypersensitivity reactions on asparaginase activity.

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.


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
Hypersensitivity Reactions
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.

Glucose Intolerance
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.

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