Incidence of non-hematologic, non-infectious grade 3 and 4 adverse reactions occurring with ERWINAZE2

Description of Event Study 1 (IM) Study 2 (IV) EMTP (IM and IV)
Collated Term N=58 N=30 N=940
Allergic reactions 5 (9%) 1 (3%) 42 (4%)
Hypersensitivity (systemic, grade 3)
Anaphylactic reaction (grade 4)
5 (9%)
0
1 (3%)
0
34 (4%)
8 (<1%)
Hyperglycemia 1 (2%) 1 (3%) 33 (4%)
Liver abnormalities 3 (5%) 0 7 (<1%)
Transaminases abnormal
Hyperbilirubinemia
3 (5%)
0
0
0
6 (<1%)
1 (<1%)
Pancreatitis 0 2 (7%) 8 (<1%)
Clinical coagulation abnormalities 0 0 9 (<1%)
Thrombosisa
Hemorrhagic disorder
0
0
0
0
8 (<1%)
1 (<1%)
Gastrointestinal symptoms not
associated with pancreatitis
1 (2%) 2 (7%) 6 (<1%)
Abdominal pain/discomfort
Nausea
Vomiting
1 (2%)
1 (2%)
1 (2%)
1 (3%)
1 (3%)
1 (3%)
3 (<1%)
3 (<1%)
3 (<1%)

aIncluding pulmonary embolism and cerebrovascular accident.

Study Design2

Study 1 was a single-arm, multi-center, open-label safety and clinical pharmacology trial (IM administration) in 58 ALL patients who were switched to intramuscular ERWINAZE following a hypersensitivity reaction to PEG-asparaginase. The Study 1 population included patients with a median age of 11 years.

Study 2, a single-arm, multi-center, open-label, pharmacokinetic (PK) study trial of intravenous administration of ERWINAZE, enrolled 30 patients; 29 were being treated for ALL and 1 for lymphoblastic lymphoma, who were switched to intravenous ERWINAZE following allergy to native E. coli asparaginase or PEG-asparaginase. The Study 2 population included patients with a median age of 7 years.

The ERWINAZE Master Treatment Protocol (EMTP) trial was an expanded access program (IM, IV, and other or unknown administration), enrolling 1368 patients with ALL or lymphoblastic lymphoma who were switched to ERWINAZE following a hypersensitivity reaction to an E. coli-derived asparaginase. Safety data were submitted for 940 patients with a median age of 9 years. The routes of administration were intramuscular (n=852), intravenous (n=29), and other or unknown (n=59).

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.

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