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The following serious adverse reactions are discussed in greater detail in other sections of the label:
- Serious hypersensitivity reactions, including anaphylaxis [see WARNINGS AND PRECAUTIONS]
- Pancreatitis [see WARNINGS AND PRECAUTIONS]
- Glucose intolerance [see WARNINGS AND PRECAUTIONS]
- Thrombosis and hemorrhage [see WARNINGS AND PRECAUTIONS]
The most common adverse reactions (incidence > 1%) with ERWINAZE treatment are serious hypersensitivity reactions, including anaphylaxis, pancreatitis, abnormal transaminases, coagulation abnormalities including thrombosis and hemorrhage, nausea and vomiting, and hyperglycemia.
Because clinical trials are conducted under controlled, but widely varying conditions, adverse reaction rates observed in clinical trials of ERWINAZE cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice. The data presented below are based on information collected from Study 1, a single-arm, multi-center, open-label, safety and clinical pharmacology trial and the ERWINAZE Master Treatment Protocol (EMTP), an expanded access program. Study 1 enrolled 58 patients treated on National Cancer Institute (NCI)-sponsored cooperative group ALL protocols who were unable to continue to receive pegaspargase due to hypersensitivity reactions. Patients received 6 doses of ERWINAZE 25,000 International Units/m2 intramuscularly on a Monday, Wednesday, and Friday schedule as a replacement for each scheduled dose of pegaspargase remaining on their original treatment protocol. The Study 1 population included patients with a median age of 10 years (2 to 18 years), 59% were male, 78% were White, 10% were Black/African American, 5% were Asian, and 5% were Hispanic or Latino. In Study 1, the planned number of ERWINAZE courses ranged from 1 to 8. Most patients, 55% (32 of 58) completed all planned therapy. Nine patients stopped therapy prior to completion, four due to allergic reactions, and five due to physician or patient choice. The remaining patients were continuing to receive ERWINAZE at the time of Study data lock. All other chemotherapy was continued according to the patient's prescribed treatment regimen [see Clinical Studies]
At the time of data cut-off, the EMTP trial had enrolled 843 patients with ALL or lymphoblastic lymphoma who received ERWINAZE after developing systemic hypersensitivity to an E. coli-derived asparaginase. Safety data were submitted for 574 patients with a median age of 9 years (1 to 66 years), 62% were male, 97% with leukemia, and 3% with lymphoma. Patients received ERWINAZE according to several schedules, and treatment center specifications with doses that ranged from 20,000 to 25,000 International Units/m2. In the EMTP trial, the planned number of doses of ERWINAZE ranged from 3 to 48 doses. Seventy-five percent of patients (434 of 575) were able to receive all planned doses to complete their prescribed treatment regimen.
In Study 1, safety information included all reported adverse events with systematic collection of the following adverse events of special interest: allergy, pancreatitis, coagulopathy (hemorrhage, thrombosis or infarct), hyperbilirubinemia, hyperglycemia, hyperlipidemia, ketoacidosis, and CNS events (hemorrhage, thrombosis or infarction, cerebral venous thrombosis). EMTP safety data were derived from case report forms that collected adverse event information. The forms specifically requested information on occurrence of allergic reactions, thrombotic events, hemorrhagic events, hepatobiliary disorders, pancreatic disorders, and hyperglycemia.
The combined incidence of non-hematologic, non-infectious, adverse reactions (all Grades) occurring with ERWINAZE in Study 1 and the EMTP trial is provided in Table 1. The incidence of Grade 3 or greater non-hematologic, non-infectious adverse reactions occurring with ERWINAZE in each individual Study is provided in Table 2.
Table 1: Per Patient Combined Incidence of Non-Hematologic
and Non-Infectious Adverse Events N=630 (Study 1 + EMTP)
|Type of Event||Specific Response||Total Patients
(N/% of total)
|Allergic Reactions||Systemic Allergic Reactions (Anaphylaxis, Hypersensitivity, Urticaria)||108 (17%)|
|Local Reactions (injection site)||3 ( < 1%)|
|Clinical Coagulation Abnormalities||Total||16 (3%)|
|Transient Ischemic Attack||1 ( < 1%)|
|Disseminated Intravascular Coagulation||1 ( < 1%)|
|Liver Abnormalities||Total||27 (4%)|
|Liver Abnormalities Abnormal Transaminase||22 (3%)|
|Gastrointestinal Symptoms Not Associated with Pancreatitis||Vomiting||15 (2%)|
|Abdominal Pain||6 (1%)|
Table 2: Per Patient Incidence of Non-Hematologic, Non-Infectious,
Grade 3 and 4 Adverse Reactions
|Description of Event||Study 1 N=58||EMTP N=572|
|Allergic Reaction / Hypersensitivity||5 (9%)||27 (5%)|
|Clinical Coagulation Abnormalities - Thrombosis||0||6 (1%)|
|Clinical Coagulation Abnormalities - Hemorrhage||0||1 ( < 1%)|
|Elevated Transaminases||1 (2%)||2 ( < 1%)|
There is a potential for immunogenicity with therapeutic proteins such as ERWINAZE. Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to ERWINAZE with the incidence of antibodies to other products may be misleading.
There is insufficient information to characterize the incidence of antibodies to ERWINAZE.
Read the Erwinaze (asparaginase erwinia chrysanthemi) Side Effects Center for a complete guide to possible side effects
No formal drug interaction studies between ERWINAZE and other drugs have been performed.
Last reviewed on RxList: 12/5/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Erwinaze Information
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