Manufacturer:

EUSA Pharma (USA), Inc.

Pharmacological Class:

Asparaginase specific enzyme.

Active Ingredient(s):

Asparaginase Erwinia chrysanthemi 10,000 IU; per vial; lyophilized pwd for IM inj after reconstitution.

Indication(s):

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.

Pharmacology:

Asparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine.

The mechanism of action of Erwinaze is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of the amino acid asparagine for their protein metabolism and survival.

Clinical Trials:

The safety and efficacy of Erwinaze was demonstrated in Study 1, a single-arm, multi-center, open-label, safety and clinical trial. Study 1 enrolled patients treated on National Cancer Institute (NCI)-sponsored cooperative group ALL protocols who were unable to continue to receive pegaspargase due to hypersensitivity reactions. The main outcome measure was determination of the proportion of patients who achieved a serum trough asparaginase level ≥0.1 IU/mL. Serum trough asparaginase activity ≥0.1 IU/mL has been demonstrated to correlate with asparagine depletion (asparagine <0.4mcg/mL or 3µM) and to serum levels that predict clinical efficacy.

Fifty-eight patients were enrolled in Study 1, of these 48 were evaluable for the main outcome measure based on availability of pharmacokinetic samples in course 1. Patients were given Erwinaze 25,000 IU/m² intramuscularly for two weeks (total 6 doses) as a replacement for each scheduled dose of pegaspargase remaining on their original treatment protocol. Study 1 met its main outcome measure of demonstrating that 100% of patients achieved serum trough asparaginase concentrations ≥0.1 IU/mL at 48 hours (n=35) or 72 hours (n=13) after the third dose. In an exploratory analysis, 80% (28/35) of those evaluated at 48 hours and 38% (5/13) evaluated at 72 hours had serum asparaginase activity levels ≥0.4 IU/mL.

Legal Classification:

Rx

Contraindication(s):

History of serious pancreatitis, thrombosis, hemorrhagic events with prior L-asparaginase therapy.

Adults & Children:

Give by IM inj (max 2mL/inj site). To substitute for a pegaspargase dose: 25,000 IU/m² three times weekly (M/W/F) for 6 doses for each planned pegaspargase dose. To substitute for a native E. coli asparaginase dose: 25,000 IU/m² for each scheduled native E. coli asparaginase dose within a treatment.

Warnings/Precautions:

Have resuscitation equipment available and other agents necessary to treat anaphylaxis. Discontinue if serious hypersensitivity reactions occur. Monitor for pancreatitis; discontinue if severe or hemorrhagic pancreatitis manifested by abdominal pain >72hrs and amylase elevation ≥2XULN occurs. Withhold therapy if mild pancreatitis; may resume after resolution. Monitor glucose levels at baseline and during therapy. Discontinue if thrombotic or hemorrhagic event occurs; may resume after resolution. Pregnancy (Cat.C). Nursing mothers: not recommended.

Adverse Reaction(s):

Serious allergic reactions (eg, anaphylaxis, hypersensitivity, urticaria), pancreatitis, abnormal transaminases, coagulation abnormalities (eg, thrombosis, hemorrhage), GI upset, hyperglycemia, fever.

How Supplied:

Vials—5

Last Updated:

12/16/2011