Erwinase
Erwinase Uses, Dosage, Side Effects, Food Interaction and all others data.
Erwinase is an asparaginase-specific enzyme derived from Erwinia chrysanthemi used as an anticancer agent. It works by depleting the stores of an important amino acid called asparagine, which is involved in DNA synthesis and cell survival of malignant cells, leading to cell death. L-asparaginase was first identified in 1963, and there are different formulations of L-asparaginase, including Asparaginase Escherichia coli and a pegylated form of this enzyme, Pegaspargase. Erwinase and Asparaginase Escherichia coli differ in their pharmacokinetic and immunogenic profiles; thus, those who are allergic to Asparaginase Escherichia coli do not cross-react to Erwinase. Studies show that substitution of Erwinia asparaginase for E. coli-derived asparaginase following an allergic reaction has been safe and effective.
Erwinase was first approved by the FDA in November 2011 to treat patients with acute lymphoblastic leukemia (ALL) who are allergic to E. coli-derived asparaginase: it has been used as part of multi-agent chemotherapy. In June 2021, the recombinant form of asparaginase Erwinia chrysanthemi was approved by the FDA as a component of a chemotherapy regimen to treat acute lymphoblastic leukemia and lymphoblastic lymphoma in adult and pediatric patients who are allergic to the E. coli-derived asparaginase.
Erwinase is an enzyme that exerts cytotoxic effects on leukemic cells by depleting the source of an amino acid asparagine, which plays a role in the proliferation, protein metabolism, and survival of malignant cells.
| Trade Name | Erwinase |
| Generic | Asparaginase Erwinia chrysanthemi |
| Asparaginase Erwinia chrysanthemi Other Names | Asparaginase (Erwinia chrysanthemi), Asparaginase (Erwinia), Asparaginase Erwinia chrysanthemi, Asparaginase Erwinia chrysanthemi (recombinant), asparaginase erwinia chrysanthemi (recombinant)-rywn, Crisantaspase, Erwinase, Erwinaze, Erwinia asparaginase, Erwinia chrysanthemi, Erwinia L-asparaginase, L-asparaginase (Erwinia), L-asparaginase, Erwinia chrysanthemi |
| Type | |
| Formula | C1546H2510N432O476S9 |
| Weight | 140000.0 Da |
| Protein binding | There is limited information on protein binding. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Erwinase is an asparagine-specific enzyme used as part of a chemotherapeutic regimen to treat patients with acute lymphoblastic leukemia and lymphoblastic lymphoma.
Asparaginase Erwinia chrysanthemi is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma in adults and children who have developed hypersensitivity to E. coli-derived asparaginase.
Erwinase is also used to associated treatment for these conditions: Acute Lymphoblastic Leukaemias (ALL)
How Erwinase works
Asparaginase Erwinia chrysanthemi is a tetrameric enzyme made up of four identical subunits, each having a molecular weight of about 35 kDa. It rapidly and completely catalyzes the deamidation reaction of L-asparagine to aspartic acid and ammonia, resulting in reduced levels of circulating asparagine in the plasma. Asparagine is essential for DNA synthesis, RNA synthesis, protein metabolism, and survival of leukemic cells ; however, they lack the asparagine synthetase enzyme and depend on an exogenous source of asparagine. Asparaginase Erwinia chrysanthemi depletes the source of asparagine for leukemic cells, resulting in the death of leukemic cells. In addition to asparagine, asparaginase Erwinia chrysanthemi also deaminates glutamine to a lesser extent.
Toxicity
There are no known cases of overdose with asparaginase Erwinia chrysanthemi. In clinical trials, the most common adverse effects were hypersensitivity reactions, pancreatic toxicity, blood clots, hemorrhage, and liver toxicity. Pancreatitis occurs in 8-14% of pediatric patients, with adolescents at the highest risk for developing this adverse event. Pancreatitis typically occurs after the first few weeks of asparaginase administration, which suggests this complication occurs from an underlying predisposition rather than a cumulative drug effect.
Food Interaction
No interactions found.Volume of Distribution
The volume of distribution of asparaginase Erwinia chrysanthemi can be up to 5 L/m2. The geometric mean (%CV) apparent volume of distribution of asparaginase Erwinia chrysanthemi (recombinant)-rywn was 1.48 L/m2 While asparaginases are not detectable in cerebrospinal fluid, asparagine in cerebrospinal fluid is depleted with systemic administration of any formulation of asparaginases.
Elimination Route
In patients two to 80 years of age, intramuscular administration of asparaginase Erwinia chrysanthemi 25,000 International Units (IU)/m2 resulted in serum trough asparaginase concentrations ≥ 0.1 IU/mL at either 48-hour (n=35) or 72-hour (n=13) post third dose. 80% of patients evaluted at 48 hours and 38% of patients evaluated at 72 hours had serum asparaginase activity levels > 0.4 IU/mL. For asparaginase Erwinia chrysanthemi (recombinant)-rywn, the median tmax is 10 hours and the mean absolute bioavailability is 37% in healthy subjects.
Half Life
The apparent half-life (%CV) of asparaginase Erwinia chrysanthemi (recombinant)-rywn is 18.2 hours (16%). Asparaginase Erwinia chrysanthemi has a shorter half-life compared with the E. coli-derived preparations.
Clearance
The geometric mean (%CV) apparent clearance of asparaginase Erwinia chrysanthemi (recombinant)-rywn is 0.31 L/hour/m (36%).
Elimination Route
Trace amounts of asparaginases are found in urine.
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