Asparaginase Erwinia chrysanthemi Asparaginase Erwinia chrysanthemi 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 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.[rx] L-asparaginase was first identified in 1963,[rx] and there are different formulations of L-asparaginase, including Asparaginase Escherichia coli and a pegylated form of this enzyme, Pegaspargase.[rx] Asparaginase Erwinia chrysanthemi and Asparaginase Escherichia coli differ in their pharmacokinetic and immunogenic profiles;[rx] thus, those who are allergic to Asparaginase Escherichia coli do not cross-react to Asparaginase Erwinia chrysanthemi.[rx] Studies show that the substitution of Erwinia asparaginase for E. coli-derived asparaginase following an allergic reaction has been safe and effective.[rx] Asparaginase is an enzyme isolated from the bacterium Escherichia coli or the bacterium Erwinia carotovora with antileukemic activity. Asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia in leukemic cells, resulting in the depletion of asparagine, inhibition of protein synthesis, cell cycle arrest in the G1 phase, and apoptosis in susceptible leukemic cell populations. Asparagine is critical to protein synthesis in leukemic cells; some leukemic cells cannot synthesize this amino acid de novo due to the absent or deficient expression of the enzyme asparagine synthase. The E. carotovora-derived form of asparaginase is typically reserved for cases of asparaginase hypersensitivity. Asparaginase is a bacterial enzyme that is used as an antineoplastic agent, largely in the therapy of acute lymphocytic leukemia. L-asparaginase has many side effects, one of which is a hepatic injury that is characterized by inhibition of hepatic protein synthesis and steatosis, which can be severe and lead to death from hepatic failure. Asparagine is an alpha-amino-acid anion that is the conjugate base of asparagine, arising from deprotonation of the carboxy group. It is a conjugate base of an asparagine. Asparaginase Erwinia chrysanthemi 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.[rx] 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.[rx] Mechanism of action 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 [rx]; 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.[rx,rx] In addition to asparagine, asparaginase Erwinia chrysanthemi also deaminates glutamine to a lesser extent.[rx] Asparaginase Erwinia chrysanthemi 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.[rx] Indications 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.[rx,rx] 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. Spectrila is indicated as a component of antineoplastic combination therapy for the treatment of acute lymphoblastic leukemia (ALL) in paediatric patients from birth to 18 years and adults. Acute Lymphoblastic Leukemia (ALL) Lymphoma, Lymphoblastic Contraindications History of serious thrombosis with prior asparaginase therapy. History of serious pancreatitis with prior asparaginase therapy. History of serious hemorrhagic events with prior asparaginase therapy. diabetes increased uric acid in the body resulting in kidney disease a type of joint disorder due to excess uric acid in the blood called gout anemia an increased risk of bleeding low levels of white blood cells obstruction of a blood vessel by a blood clot bleeding acute inflammation of the pancreas high amount of bilirubin in the blood high amount of uric acid in the blood abnormally high levels of nitrogen-containing compounds in your blood abnormal liver function tests pregnancy a patient who is producing milk and breastfeeding a type of brain disorder called posterior reversible encephalopathy syndrome You Might Also Read Uses Indications of Botulinum ToxinDosage Strengths: 10000 intl units; rywn recombinant 10 mg/0.5 mL Acute Lymphoblastic Leukemia To substitute for a dose of pegaspargase: 25,000 International Units/m2 intramuscularly three times a week (Monday/Wednesday/Friday) for six doses for each planned dose of pegaspargase. To substitute for a dose of native E. coli asparaginase: 25,000 International Units/m2 administered intramuscularly for each scheduled dose of native E. coli asparaginase within a treatment regimen. Limit the volume of reconstitution at a single injection site to 2 mL; if reconstituted dose to be administered is greater than 2 mL, use multiple injection sites. If a partial vial is used, do not save or reuse the unused drug for later administration. Discard unused portions. Pediatric Dose for Acute Lymphoblastic Leukemia To substitute for a dose of pegaspargase: 25,000 International Units/m2 intramuscularly three times a week (Monday/Wednesday/Friday) for six doses for each planned dose of pegaspargase. To substitute for a dose of native E. coli asparaginase: 25,000 International Units/m2 administered intramuscularly for each scheduled dose of native E. coli asparaginase within a treatment. Limit the volume of reconstitution at a single injection site to 2 mL; if the reconstituted dose to be administered is greater than 2 mL, use multiple injection sites. If a partial vial is used, do not save or reuse the unused drug for later administration. Discard unused portions. Side Effects The Most Common nausea diarrhea constipation muscle or bone pain headache tiredness fever, chills, cough, or other signs of infection loss of appetite difficulty falling asleep or staying asleep swelling of the face, lips, eyes, arms, or legs hives itching rash or redness shortness of breath or difficulty breathing yellowing of skin or eyes, pain in the upper right part of the stomach, dark-colored urine, or loss of appetite unusual bleeding or bruising blood in urine headache, arm or leg swelling, shortness of breath, and chest pain severe abdominal pain, fever, weight loss, nausea, and vomiting More common Agitation back pain black, tarry stools bleeding gums bloating blood in the urine or stools blurred vision chest pain chills coma confusion constipation cough or hoarseness difficulty in walking dizziness drooping eyelids drowsiness dry mouth lightheadedness fainting fast heartbeat fever flushed, dry skin fruit-like breath odor hallucinations headache increased hunger increased menstrual flow or vaginal bleeding increased thirst increased urination indigestion irritability jaw pain lower back or side pain mood or mental changes nosebleeds numbness or tingling in the fingers and toes pain in the fingers and toes pain in the testicles pains in the chest, groin, or legs, especially calves of the legs pains in stomach, side, or abdomen, possibly radiating to the back painful or difficult urination pale skin paralysis pinpoint red spots on the skin prolonged bleeding from cuts rapid, shallow breathing seizures severe headaches of sudden onset sleepiness or unusual drowsiness sore throat sores, ulcers, or white spots on the lips or in the mouth stiff neck stomach pain sudden loss of coordination sudden onset of slurred speech sudden vision changes sweating swollen glands trouble breathing unexplained weight loss unusual bleeding or bruising unusual tiredness or weakness vomiting yellow eyes or skin Rare Chest tightness difficulty swallowing dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position hives, itching, skin rash increase in the frequency of seizures loss of appetite loss of consciousness puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue Diarrhea nervousness pounding in the ears slow or fast heartbeat unpleasant breath odor vomiting of blood Bleeding, blistering, burning, coldness, discoloration of the skin, the feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site Drug Interactions DRUG INTERACTION Allantoin The therapeutic efficacy of Allantoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Articaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Bupivacaine. Butacaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Butacaine. Butamben The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Butamben. Capsaicin The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Capsaicin. Carbamazepine The therapeutic efficacy of Carbamazepine can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Chloroprocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Chloroprocaine. Cinchocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Cinchocaine. Cocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Cocaine. Dantrolene The therapeutic efficacy of Dantrolene can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Darbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Asparaginase Erwinia chrysanthemi. Dexamethasone The serum concentration of Dexamethasone can be increased when it is combined with Asparaginase Erwinia chrysanthemi. Diphenhydramine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Diphenhydramine. Dyclonine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Dyclonine. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Asparaginase Erwinia chrysanthemi. Ethotoin The therapeutic efficacy of Ethotoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Ethyl chloride The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Ethyl chloride. Etidocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Etidocaine. Fosphenytoin The therapeutic efficacy of Fosphenytoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Furosemide The therapeutic efficacy of Furosemide can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Heparin The therapeutic efficacy of Heparin can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Imatinib The risk or severity of liver damage can be increased when Asparaginase Erwinia chrysanthemi is combined with Imatinib. Levobupivacaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Levobupivacaine. Levothyroxine The therapeutic efficacy of Levothyroxine can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Lidocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Lidocaine. Liothyronine The therapeutic efficacy of Liothyronine can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Liotrix The therapeutic efficacy of Liotrix can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Meclofenamic acid The therapeutic efficacy of Meclofenamic acid can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Meloxicam The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Meloxicam. Mephenytoin The therapeutic efficacy of Mephenytoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Mepivacaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Mepivacaine. Methotrexate The therapeutic efficacy of Methotrexate can be decreased when used in combination with Asparaginase Erwinia chrysanthemi. Methoxy The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Asparaginase Erwinia chrysanthemi. Nitrofurantoin The therapeutic efficacy of Nitrofurantoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Oxetacaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Oxetacaine. Oxybuprocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Oxybuprocaine. Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Asparaginase Erwinia chrysanthemi. Pexidartinib Asparaginase Erwinia chrysanthemi may increase the hepatotoxic activities of Pexidartinib. Phenol The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Phenol. Phenytoin The therapeutic efficacy of Phenytoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi. Pramocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Pramocaine. Prilocaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Prilocaine. Procaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Procaine. Proparacaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Proparacaine. Propoxycaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Propoxycaine. Ropivacaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Ropivacaine. Tetracaine The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Tetracaine. Valoctocogene The therapeutic efficacy of Valoctocogene roxaparvovec can be decreased when used in combination with Asparaginase Erwinia chrysanthemi. You Might Also Read Dactinomycin - Uses, Dosage, Side Effects, InteractionPregnancy and Lactation US FDA pregnancy category: C Pregnancy Use is recommended only if clearly needed and the benefit outweighs the risk. In animal studies, maternal toxicities of decreased body weight and decreased body weight gain and fetal findings of increased incidence of partially undescended thymic tissue, increased post-implantation loss, decreased number of live fetuses, and gross abnormalities were observed. There are no controlled data in human pregnancy. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant the use of the drug in pregnant women despite potential risks. Lactation Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Data not available The effects on the nursing infant are unknown. How should this medicine be used? Asparaginase erwinia chrysanthemi (recombinant)-rywn comes as a solution (liquid) to be given intramuscularly (injected into a muscle) by a doctor or nurse in a medical facility. It is usually given every 48 hours. The length of treatment depends on how you respond to the medication. Your doctor may need to delay your treatment or stop your treatment if you experience certain side effects. It is important for you to tell your doctor how you are feeling during your treatment with asparaginase erwinia chrysanthemi (recombinant)-rywn injection. Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient. You Might Also Read Salicylic Acid - Indications, Contraindications Other uses for this medicine This medication may be prescribed for other uses; ask your doctor or pharmacist for more information. What special precautions should I follow? Before receiving asparaginase erwinia chrysanthemi (recombinant)-rywn, tell your doctor and pharmacist if you are allergic to asparaginase erwinia chrysanthemi (recombinant)-rywn, any other medications, or any of the ingredients in asparaginase erwinia chrysanthemi (recombinant)-rywn. Ask your pharmacist for a list of the ingredients. tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had pancreatitis (swelling of the pancreas), blood clots, or severe bleeding, especially if these happened during treatment with asparaginase (Elspar). Your doctor probably will not want you to receive asparaginase erwinia chrysanthemi (recombinant)-rywn. tell your doctor if you have or have ever had medical conditions. tell your doctor if you are pregnant or plan to become pregnant. You will need to take a pregnancy test before you start treatment and use a non-hormonal birth control (device that blocks sperm from entering the uterus such as a condom or a diaphragm) during your treatment and for 3 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you become pregnant while receiving asparaginase erwinia chrysanthemi (recombinant)-rywn, call your doctor immediately. Asparaginase erwinia chrysanthemi (recombinant)-rywn may harm the fetus. tell your doctor if you are breastfeeding. You should not breastfeed while you are receiving asparaginase erwinia chrysanthemi (recombinant)-rywn and for 1 week after the final dose. References https://www.cancer.gov/about-cancer/treatment/drugs/asparaginase-erwinia-chrysanthemi https://go.drugbank.com/drugs/DB08886 https://pubchem.ncbi.nlm.nih.gov/bioassay/481838/version/3.1 https://www.mayoclinic.org/drugs-supplements/asparaginase-erwinia-chrysanthemi-injection-route/side-effects/drg-20075340 https://medlineplus.gov/druginfo/meds/a621042.html https://www.drugs.com/mtm/asparaginase-erwinia-chrysanthemi.html ChEBI http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:32660 ChEBI Ontology http://www.ebi.ac.uk/chebi/userManualForward.do#ChEBI%20Ontology LiverTox LICENSE https://www.nlm.nih.gov/copyright.html Asparaginase https://www.ncbi.nlm.nih.gov/books/n/livertox/Asparaginase/ NCI Thesaurus (NCIt) https://www.cancer.gov/policies/copyright-reuse https://ncithesaurus.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C286 ChemIDplus LICENSE https://www.nlm.nih.gov/copyright.html Asparaginase [USAN] https://chem.nlm.nih.gov/chemidplus/sid/0009015683 European Chemicals Agency (ECHA) https://echa.europa.eu/web/guest/legal-notice Asparaginase https://echa.europa.eu/substance-information/-/substanceinfo/100.029.774 Asparaginase https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/42570 ClinicalTrials.gov https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use https://clinicaltrials.gov/ Drug Induced Liver Injury Rank (DILIrank) Dataset https://www.fda.gov/about-fda/about-website/website-policies#linking asparaginase https://www.fda.gov/science-research/liver-toxicity-knowledge-base-ltkb/drug-induced-liver-injury-rank-dilirank-dataset EPA DSSTox LICENSE https://www.epa.gov/privacy/privacy-act-laws-policies-and-resources Asparaginase https://comptox.epa.gov/dashboard/DTXSID3042554 EU Clinical Trials Register https://www.clinicaltrialsregister.eu/ European Medicines Agency (EMA) https://www.ema.europa.eu/en/about-us/legal-notice Spectrila (EMEA/H/C/002661) https://www.ema.europa.eu/en/medicines/human/EPAR/spectrila WHO Anatomical Therapeutic Chemical (ATC) Classification https://www.whocc.no/copyright_disclaimer/ https://www.whocc.no/atc/ ATC Code https://www.whocc.no/atc_ddd_index/ FDA Purple Book Elspar https://purplebooksearch.fda.gov/productdetails?query=101063 National Drug Code (NDC) Directory https://www.fda.gov/about-fda/about-website/website-policies#linking ASPARAGINASE https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory NLM RxNorm Terminology https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html asparaginase https://rxnav.nlm.nih.gov/id/rxnorm/1156 WHO Model Lists of Essential Medicines https://www.who.int/about/who-we-are/publishing-policies/copyright Asparaginase https://list.essentialmeds.org/medicines/72 Wikidata LICENSE CCZero https://creativecommons.org/publicdomain/zero/1.0/ asparaginate https://www.wikidata.org/wiki/Q27115042 Medical Subject Headings (MeSH) https://www.nlm.nih.gov/copyright.html Asparaginase https://www.ncbi.nlm.nih.gov/mesh/68001215 MeSH Tree http://www.nlm.nih.gov/mesh/meshhome.html Antineoplastic Agents https://www.ncbi.nlm.nih.gov/mesh/68000970 PubChem https://pubchem.ncbi.nlm.nih.gov UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) GHS Classification Tree http://www.unece.org/trans/danger/publi/ghs/ghs_welcome_e.html PATENTSCOPE (WIPO) SID 390068549 https://pubchem.ncbi.nlm.nih.gov/substance/390068549 Show More