Hypersensitivity reactions could potentially lead to interruptions in asparaginase treatment2,4

  • The majority of hypersensitivity reactions occur following induction7
  • Patients unable to complete a scheduled dose of asparaginase due to a hypersensitivity reaction may not achieve adequate asparagine depletion between doses12

Protocol AALL1131: Scheduled doses of PEG-asparaginase14

Scheduled dosing of PEG-asparaginase

  • A hypersensitivity reaction that interferes with the administration of asparaginase could result in a prolonged time period between complete consecutive doses of asparaginase

Patients rechallenged with the same asparaginase preparation following a hypersensitivity reaction may develop a subsequent reaction15,16

Data suggest that premedication with antihistamines or corticosteroids prior to a rechallenge may not eliminate the risk of a subsequent reaction15,16

  • In a clinical trial, 22 patients developed hypersensitivity to E. coli asparaginase15
    • 10 of the 22 were switched to Erwinia asparaginase
    • The remaining 12 patients were premedicated and rechallenged with E. coli asparaginase
      • 10 of the 12 (83%) who were rechallenged had a subsequent hypersensitivity reaction

Study Design

A clinical trial in 35 newly diagnosed patients with ALL evaluated plasma anti-asparaginase antibody concentrations (as measured by enzyme-linked immunosorbent assay [ELISA]) during native E. coli asparaginase treatment. Of the 22 patients who developed allergy, 12 continued with E. coli asparaginase and were premedicated with diphenhydramine or corticosteroid; 10 of those patients reacted again and were switched to Erwinia asparaginase. The remaining 10 of the 22 reacting patients were switched to Erwinia asparaginase as a control with 3 patients receiving premedication; 2 of these 3 patients were able to remain on Erwinia asparaginase with premedication, whereas 1 was switched to PEG. The patient experienced a hypersensitivity reaction to all 3 asparaginase preparations. In this study, 25% of patients switched to Erwinia asparaginase had a subsequent reaction.15

Indication
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

Contraindications
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.

Pancreatitis
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.

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.