Pegaspargase Drugbank ID DB 00059 Protein chemical formula

Pegaspargase Drugbank ID: DB 00059 Protein chemical formula : C 1377 H 2208 N 382 O 442 S 17 Protein average weight : 31731. 9000

Description : Pegylated L-asparagine amidohydrolase from E. coli. Pegylation substantially (by a factor of 4) extends the protein half life. Indication : For treatment of acute lymphoblastic leukemia Pharmacodynamics : In a significant number of patients with acute leukemia, the malignant cells are dependent on an exogenous source of asparagine for survival. Normal cells, however, are able to synthesize asparagine and thus are affected less by the rapid depletion produced by treatment with the enzyme asparaginase. Oncaspar exploits a metabolic defect in asparagine synthesis of some malignant cells. Mechanism Of Action : Pegaspargase, more effective than asparaginase, converts asparagine to aspartic acid and ammonia. It facilitates production of oxaloacetate which is needed for general cellular metabolism. Some malignant cells lose the ability to produce asparagine and so the loss of exogenous sources of asparagine leads to cell death. Categories : Antineoplastic Agents Affected Organism : Humans and other mammals

Drug Interactions: Denosumab : Monitor therapy due to increased immunosuppressive effect and risk of infections. Leflunomide : Immunosuppressants can increase toxic effects of leflunomide such as hematologic toxicity. Natalizumab : Avoid combination because of increased immunosuppressants and risk of infections. Pimecrolimus : Avoid combination because pimecrolimus enhances the adverse effects of immunosuppressants. Roflumilast : Consider therapy modification because pegaspargase enhances the immunosuppressive effect of roflumilast. Sipuleucel-T Monitor therapy because pegaspargase may diminish therapeutic effect of sipuleucel-T. Tacrolimus : Tacrolimus enhances adverse effects of pegaspargase therefore the combination should be avoided. Tofacitinib : Avoid combination due to enhanced immunosuppressive effect of tofacitinib. Trastuzumab : Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Sequence : MEFFKKTALAALVMGFSGAALALPNITILATGGTIAGGGDSATKSNYTVGKVGVENLVNAVPQLKDIANV KGEQVVNIGSQDMNDNVWLTLAKKINTDCDKTDGFVITHGTDTMEETAYFLDLTVKCDKPVVMVGAM RPSTSMSADGPFNLYNAVVTAADKASANRGVLVVMNDTVLDGRDVTKTNTTDVATFKSVNYGPLGYIH NGKIDYQRTPARKHTSDTPFDVSKLNELPKVGIVYNYANASDLPAKALVDAGYDGIVSAGVGNGNLYKSV FDTLATAAKTGTAVVRSSRVPTGATTQDAEVDDAKYGFVASGTLNPQKARVLLQLALTQTKDPQQIQQI FNQY Targets : L-asparagine

Brands : Oncaspar Company : Enzon Inc Description : Oncaspar® (pegaspargase) is L-asparaginase (L-asparagine amidohydrolase) that is covalently conjugated to monomethoxypolyethylene glycol (m. PEG). L-asparaginase is a tetrameric enzyme that is produced endogenously by E. coli and consists of identical 34. 5 k. Da subunits. Approximately 69 to 82 molecules of m. PEG are linked to Lasparaginase; the molecular weight of each m. PEG molecule is about 5 k. Da. Oncaspar® activity is expressed in International Units. One International Unit of L-asparaginase is defined as the amount of enzyme required to generate 1 micromole of ammonia per minute at p. H 7. 3 and 37°C Used For/Prescribed for : Oncaspar® is indicated as a component of a multiagent chemotherapeutic regimen for the first line treatment of patients with Acute Lymphoblastic Leukemia (ALL). Formulation : Oncaspar® is supplied as a clear, colorless, preservative-free, isotonic sterile solution in phosphate-buffered saline, p. H 7. 3. Each milliliter contains 750 ± 150 International Units of pegaspargase, dibasic sodium phosphate, USP (5. 58 mg), monobasic sodium phosphate, USP, (1. 20 mg) and sodium chloride, USP (8. 50 mg) in water for injection, USP. Form : solution Route of administration : intravenous or intramuscular administration

Dosage: The recommended dose of Oncaspar® is 2, 500 International Units/m² intramuscularly or intravenously. Oncaspar® should be administered no more frequently than every 14 days. When Oncaspar® is administered intramuscularly, the volume at a single injection site should be limited to 2 m. L. If the volume to be administered is greater than 2 m. L, multiple injection sites should be used. Oncaspar® does not contain a preservative. Use only one dose per vial; discard unused product. When administered intravenously, Oncaspar® should be given over a period of 1 to 2 hours in 100 m. L of sodium chloride or dextrose injection 5%, through an infusion that is already running. After the solution is diluted for intravenous use, the solution should be used immediately. If immediate use is not possible, the diluted solution should be stored refrigerated at 2°C to 8°C (36°F to 46°F). Storage after dilution should not exceed 48 hours from the time of preparation to completion of administration. Contraindication : History of serious allergic reactions to Oncaspar®. History of serious thrombosis with prior L-asparaginase therapy. History of pancreatitis with prior L-asparaginase therapy. History of serious hemorrhagic events with prior L-asparaginase therapy. Side effects : Hypersensitivity reactions, coagulopathy, hyperglycemia, elevated serum transaminase concentrations, hyperbilirubinemia, pancreatitis, CNS thrombosis. No apparent difference in adverse effects following IV versus IM administration. Drug Interaction : A total of 136 drugs (572 brand generic names) are known to interact with Oncaspar (pegaspargase). 2 major drug interactions (4 brand generic names) 134 moderate drug interactions (568 brand generic names)

General References # Graham ML: Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev. 2003 Sep 26; 55(10): 1293 -302. "Pubmed": http: //www. ncbi. nlm. nih. gov/pubmed/14499708

Refrence http: //www. fda. gov/About. FDA/Centers. Offices/Officeof. Medical. Pr oductsand. Tobacco/CDER/ucm 095609. htm http: //www. oncaspar. com/ http: //www. rxlist. com/oncaspar-drug. htm http: //www. drugs. com/monograph/oncaspar. html