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| Primary information |
|---|
| ID | 10337 |
| Therapeutic ID | Th1048 |
| Protein Name | Pegaspargase |
| Sequence | >Th1048_Pegaspargase
MEFFKKTALAALVMGFSGAALALPNITILATGGTIAGGGDSATKSNYTVGKVGVENLVNAVPQLKDIANVKGEQVVNIGSQDMNDNVWLTLAKKINTDCDKTDGFVITHGTDTMEETAYFLDLTVKCDKPVVMVGAMRPSTSMSADGPFNLYNAVVTAADKASANRGVLVVMNDTVLDGRDVTKTNTTDVATFKSVNYGPLGYIHNGKIDYQRTPARKHTSDTPFDVSKLNELPKVGIVYNYANASDLPAKALVDAGYDGIVSAGVGNGNLYKSVFDTLATAAKTGTAVVRSSRVPTGATTQDAEVDDAKYGFVASGTLNPQKARVLLQLALTQTKDPQQIQQIFNQY
|
| Molecular Weight | 31731.9 |
| Chemical Formula | C1377H2208N382O442S17 |
| Isoelectric Point | 4.67 |
| Hydrophobicity | 0.059 |
| Melting point | NA |
| Half-life | IM: ~6 days |
| Description | Pegylated L-asparagine amidohydrolase from E. coli. Pegylation substantially (by a factor of 4) extends the protein half life. |
| Indication/Disease | 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. |
| Toxicity | Adverse effects that occur more than 10% of the time include hepatotoxicity as it is known to increase serum transaminases (ALT, AST). Also known to induce hypersensitivity reactions including anaphylaxis, erythema and bronchospasm. |
| Metabolism | NA |
| Absorption | Onset of Asparagine depletion by IM is within 4 days Time to peak: IM: 3 to 4 days |
| IV: Adults (asparaginase naive): 2.4 L/m2 Distributes into CSF (reportedly reducing CSF asparagine concentrations to a similar extent as asparaginase |
| Clearance | NA |
| Categories | Alcohols, Amidohydrolases, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Asparaginase, Asparagine-specific Enzyme, Compounds used in a research, industrial, or household setting, Delayed-Action Preparations, Enzymes, Enzymes and Coenzymes, Ethylene Glycols, Glycols, Hydrolases, Immunosuppressive Agents, Macromolecular Substances, Pegylated agents, Polymers, Thyroxine-binding globulin inhibitors |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. |
| Target | L-asparagine |
| Brand Name | Oncaspar |
| Company | Enzon Inc, Servier Pharmaceuticals LLC, Sigma Tau Pharmaceuticals, Inc., Les Laboratoires Servier, Baxalta US Inc. |
| Brand Description | Enzon Inc, Servier Pharmaceuticals LLC, Sigma Tau Pharmaceuticals, Inc., Les Laboratoires Servier, Baxalta US Inc. |
| Prescribed For | Oncaspar is indicated as a component of a multi-agent chemotherapeutic regimen for the first line treatment of patients with Acute Lymphoblastic Leukemia (ALL). |
| Chemical Name | NA |
| Formulation | Oncaspar is supplied as a clear, colorless, preservative-free, isotonic sterile solution in phosphate-buffered saline, pH 7.3. Each milliliter contains 750 ± 150 International Units of pegaspargase, dibasic sodium phosphate, USP (5.58 mg), monobasic sodiu |
| Physical Appearance | Solution |
| Route of Administration | Intravenous or intramuSubcutaneousular administrat |
| Recommended Dosage | The recommended dose of Oncaspar is 2,500 International Units/m_ 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 2ml. |
| 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. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |