asparaginase Erwinia chrysanthemi recombinant

Action and Spectrum

Actions and Spectrum: 

asparaginase Erwinia chrysanthemi recombinant, also known as Erwinase, is a medication generally used to treat acute lymphoblastic leukemia (ALL) in certain situations. It is derived from the bacterium Erwinia chrysanthemi through recombinant DNA technology. 

Action:

asparaginase is an enzyme that breaks down the amino acid asparagine into aspartic acid and ammonia. Asparagine is essential for the growth and proliferation of leukemia cells. By depleting the levels of asparagine in the blood, asparaginase inhibits the ability of leukemia cells to synthesize proteins necessary for their survival. This leads to the selective death of leukemic cells, helping to control the progression of ALL. 

Spectrum:

asparaginase Erwinia chrysanthemi recombinant is used explicitly as a 2nd line treatment option in patients with ALL who have developed an allergic reaction or intolerance to the first-line asparaginase derived from Escherichia coli. It is an alternative therapeutic agent that can be employed when patients cannot tolerate other forms of asparaginase. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Neuropathy peripheral (15%) 

Stomatitis (21%) 

Febrile neutropenia (24%) 

Fatigue (36%) 

Dehydration (15%) 

Nausea (46%) 

Hypersensitivity (24%) 

Abdominal pain (18%) 

Insomnia (15%) 

Musculoskeletal pain (39%) 

Abnormal liver test (70%) 

Pyrexia (27%) 

Cough (15%) 

Diarrhea (18%) 

Infection (30%) 

Headache (30%) 

Bleeding (21%) 

Tachycardia (18%) 

Constipation (15%) 

Decreased appetite (21%) 

Hyperglycemia (21%) 

Febrile neutropenia (24%) 

Infection (12%) 

1-10% 

Diarrhea (6%) 

Pyrexia (6%) 

Nausea (9%) 

Musculoskeletal pain (6%) 

Stomatitis (9%) 

Hypersensitivity (6%) 

Fatigue (3%) 

Dehydration (9%) 

Decreased appetite (6%) 

Hyperglycemia (3%) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

The asparaginase Erwinia chrysanthemi recombinant has specific contraindications, factors, or conditions that make the use of the medically inadvisable. Here are the known contraindications for Erwinase: 

• History of severe hypersensitivity reactions: Patients with a history of serious hypersensitivity (allergic) reactions, including anaphylaxis, to asparaginase products should not receive Erwinase. Hypersensitivity reactions can be life-threatening, and using Erwinase in such patients could lead to severe adverse effects. 
• History of pancreatitis: Patients with a history of pancreatitis, which is inflammation of the pancreas, should not receive Erwinase. The medication can increase the risk of pancreatitis or worsen existing pancreatic conditions. 

Caution 

Specific cautions may apply to asparaginase medications: 

• Hypersensitivity Reactions: asparaginase medications, including Erwinase, can potentially cause hypersensitivity reactions ranging from mild to severe, including anaphylaxis. Close monitoring for allergic reactions is necessary during treatment. Patients with a history of hypersensitivity to asparaginase or other related substances may be at higher risk. 
• Coagulopathy: asparaginase can affect blood clotting function, leading to bleeding or disorders. Close monitoring of coagulation parameters, like PT (prothrombin time) and activated partial thromboplastin time (aPTT), may be necessary during treatment. 
• Liver Dysfunction: Erwinase can potentially cause liver toxicity. Liver function tests should be regularly monitored during treatment, and caution should be exercised in patients with pre-existing liver dysfunction. 
• Pancreatitis: asparaginase medications, including Erwinase, have been associated with pancreatitis. Monitoring for signs and symptoms of pancreatitis, such as abdominal pain, nausea, and vomiting, is essential during treatment. 
• Glucose Intolerance: asparaginase can interfere with glucose metabolism and lead to glucose intolerance or hyperglycemia. Blood glucose levels should be monitored regularly in patients receiving treatment. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

asparaginase Erwinia chrysanthemi recombinant is an enzyme-based medication for treating acute lymphoblastic leukemia (ALL). Here is an overview of its pharmacology: 

Erwinase is an asparagine-specific enzyme hydrolyzes the amino acid asparagine into aspartic acid and ammonia. Asparagine is essential for the growth and survival of leukemic cells in ALL. By depleting the levels of asparagine in the blood, Erwinase deprives leukemic cells of this critical nutrient, leading to inhibition of protein synthesis and, eventually, selective death of the leukemic cells. 

Pharmacodynamics: 

Mechanism of action: Its action is related to the depletion of the amino acid asparagine. 

• Asparagine Depletion: Erwinase is an asparagine-specific enzyme. It catalyzes the hydrolysis of the amino acid asparagine into aspartic acid and ammonia. Asparagine is necessary for the growth and survival of leukemic cells, including those in ALL. 
• Inhibition of Protein Synthesis: Leukemic cells cannot synthesize asparagine due to a deficiency of the enzyme asparagine synthetase. Therefore, they rely on exogenous asparagine from the blood for protein synthesis and proliferation. By depleting the levels of asparagine in the blood, Erwinase restricts the availability of this essential nutrient to leukemic cells. 
• Selective Toxicity: Unlike normal cells in the body, leukemic cells lack sufficient levels of asparagine synthetase and cannot produce asparagine internally. Consequently, the depletion of asparagine by Erwinase selectively affects leukemic cells while sparing normal cells, as they can synthesize asparagine independently. 

Pharmacokinetics: 

Absorption 

Erwinase can be administered via intramuscular (IM) or intravenous (IV) routes. When administered IM, the absorption rate of Erwinase is variable. Peak plasma concentrations are typically reached within a few hours after IM administration. Factors such as injection site, blood flow, and individual patient characteristics may influence the absorption process. 

Distribution 

Erwinase is distributed in the extracellular fluid compartment. It does not significantly cross the blood-brain barrier. The exact distribution characteristics of Erwinase in various tissues and organs are not extensively documented. 

Metabolism 

Erwinase is primarily metabolized by proteolytic enzymes in the body. These enzymes break down Erwinase into smaller peptide fragments. The specific details of the metabolic pathways and the enzymes involved in the metabolism of Erwinase have yet to be extensively studied. 

Elimination and Excretion 

The elimination of Erwinase occurs primarily through renal excretion. After metabolism and breakdown, the resulting peptide fragments are eliminated via the kidneys as metabolites. A smaller fraction of Erwinase may be eliminated in feces, although the exact percentage is not well-documented. 

Adminstartion

Administration: 

Intramuscular administration 

asparaginase Erwinia chrysanthemi recombinant (Erwinase) is administered by a healthcare professional, typically in a hospital or clinical setting. The specific administration instructions may vary based on the patient’s condition and the healthcare provider’s guidance. Here are some general guidelines for the administration of Erwinase: 

• Route of Administration: Erwinase is usually administered as an intramuscular (IM) injection. It is injected into the muscle, typically the thigh or upper arm. It may also be given intravenously (IV), depending on the healthcare provider’s preference and the patient’s situation. 
• Dosage and Schedule: The dosage and schedule of Erwinase will be determined by the treating physician based on factors like the patient’s age, weight, overall health, and the specific treatment protocol being followed. The medication is typically given several times a week, with the frequency and duration of treatment varying depending on the individual treatment plan. 
• Preparation and Administration: Erwinase is supplied as a sterile lyophilized powder that needs to be reconstituted before administration. The healthcare provider will follow the appropriate procedures to prepare the medication according to the instructions provided with the product. It is essential to follow aseptic techniques to maintain sterility during preparation and administration. 
• Monitoring and Follow-up: Regular monitoring of blood counts, liver function, coagulation parameters, and other relevant laboratory tests may be necessary during treatment with Erwinase. The healthcare provider will determine the frequency of monitoring based on the patient’s condition and treatment response. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: asparaginase Erwinia chrysanthemi recombinant 

Pronounced: [ as-PAR-a-jin-ase-er-WIN-ee-a-kri-SAN-the-mee ] 

Why do we use asparaginase Erwinia chrysanthemi recombinant? 

asparaginase Erwinia chrysanthemi recombinant (Erwinase) is primarily used in treating acute lymphoblastic leukemia (ALL) in certain situations. Here are the specific uses of Erwinase: 

• ALL Treatment: Erwinase is indicated for use as a component of multi-agent chemotherapeutic regimens in treating ALL, specifically in patients who have developed hypersensitivity or intolerance to E. coli-derived asparaginase. It is used as a second-line or alternative therapy when patients cannot tolerate other forms of asparaginase. 
• Hypersensitivity or Intolerance to E. coli-derived asparaginase: Some patients with ALL may develop allergic reactions or experience intolerance to asparaginase derived from Escherichia coli, commonly used as a first-line treatment. In these cases, Erwinase can be used as a substitute to provide the necessary asparaginase activity. 

It’s important to note that Erwinase is specifically indicated for treating ALL and is not used for other types of cancers or medical conditions. A qualified healthcare professional should determine the specific usage and treatment plan involving Erwinase based on the individual patient’s condition, medical history, and treatment protocol.