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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyPegaspargase
Identification
- Name
- Pegaspargase
- Accession Number
- DB00059 (BTD00079, BIOD00079)
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Description
Pegylated L-asparagine amidohydrolase from E. coli. Pegylation substantially (by a factor of 4) extends the protein half life.
- Protein structure
- Protein chemical formula
- C1377H2208N382O442S17
- Protein average weight
- 31731.9 Da
- Sequences
>DB00059 sequence MEFFKKTALAALVMGFSGAALALPNITILATGGTIAGGGDSATKSNYTVGKVGVENLVNA VPQLKDIANVKGEQVVNIGSQDMNDNVWLTLAKKINTDCDKTDGFVITHGTDTMEETAYF LDLTVKCDKPVVMVGAMRPSTSMSADGPFNLYNAVVTAADKASANRGVLVVMNDTVLDGR DVTKTNTTDVATFKSVNYGPLGYIHNGKIDYQRTPARKHTSDTPFDVSKLNELPKVGIVY NYANASDLPAKALVDAGYDGIVSAGVGNGNLYKSVFDTLATAAKTGTAVVRSSRVPTGAT TQDAEVDDAKYGFVASGTLNPQKARVLLQLALTQTKDPQQIQQIFNQY
Download FASTA Format- Synonyms
- Peg-asparaginase
- Peg/L-asparaginase
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Oncaspar Liquid 750 unit Intramuscular; Intravenous Aventis Pharma Ltd. 1998-10-13 2004-01-02 Canada 
Oncaspar Injection, solution 750 [iU]/mL Intramuscular; Intravenous Baxalta Canada Corporation 1994-02-01 Not applicable US 
Oncaspar Injection, solution 750 [iU]/mL Intramuscular; Intravenous Sigma Tau Pharmaceuticals, Inc. 1994-02-01 2016-11-30 US Oncaspar Solution 750 unit Intramuscular; Intravenous Baxalta Canada Corporation 2017-06-01 Not applicable Canada Oncaspar Use Injection, solution 750 U/ml Baxalta Innovations Gmb H 2016-01-14 Not applicable EU 
- Categories
- Alcohols
- Amidohydrolases
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Asparagine-specific Enzyme
- Biomedical and Dental Materials
- Delayed-Action Preparations
- Enzymes
- Enzymes and Coenzymes
- Enzymes, Immobilized
- Ethylene Glycols
- Glycols
- Hydrolases
- Immunosuppressive Agents
- Macromolecular Substances
- Polymers
- UNII
- 7D96IR0PPM
- CAS number
- 130167-69-0
Pharmacology
- Indication
For treatment of acute lymphoblastic leukemia
- Structured Indications
- 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.
Target Actions Organism AL-asparagine other/unknownHuman - Absorption
Onset of Asparagine depletion by IM is within 4 days Time to peak: IM: 3 to 4 days
- Volume of distribution
IV: Adults (asparaginase naive): 2.4 L/m2 Distributes into CSF (reportedly reducing CSF asparagine concentrations to a similar extent as asparaginase
- Protein binding
- Not Available
- Metabolism
- Not Available
- Route of elimination
- Not Available
- Half life
IM: ~6 days; half-life decreased to ~3 days (range: 1.4 to 5 days) in patients with previous hypersensitivity to native L-asparaginase; IV: Adults (asparaginase naive): 7 days
- Clearance
- Not Available
- 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.
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Pegaspargase. Approved Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Pegaspargase. Experimental Ancestim The risk or severity of cytotoxicity can be increased when Ancestim is combined with Pegaspargase. Approved, Investigational, Withdrawn Anthrax immune globulin human The risk or severity of adverse effects can be increased when Pegaspargase is combined with Anthrax immune globulin human. Approved Bacillus calmette-guerin substrain connaught live antigen The risk or severity of adverse effects can be increased when Pegaspargase is combined with Bacillus calmette-guerin substrain connaught live antigen. Approved, Investigational Bacillus calmette-guerin substrain tice live antigen The risk or severity of adverse effects can be increased when Pegaspargase is combined with Bacillus calmette-guerin substrain tice live antigen. Approved BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Pegaspargase. Investigational Bevacizumab Bevacizumab may increase the cardiotoxic activities of Pegaspargase. Approved, Investigational Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Pegaspargase. Approved Clostridium tetani toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pegaspargase is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated). Approved Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pegaspargase is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated). Approved Cyclophosphamide Cyclophosphamide may increase the cardiotoxic activities of Pegaspargase. Approved, Investigational Cymarin Cymarin may decrease the cardiotoxic activities of Pegaspargase. Experimental Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Pegaspargase. Approved Deslanoside Deslanoside may decrease the cardiotoxic activities of Pegaspargase. Approved Digitoxin Digitoxin may decrease the cardiotoxic activities of Pegaspargase. Approved, Investigational Digoxin Digoxin may decrease the cardiotoxic activities of Pegaspargase. Approved Digoxin Immune Fab (Ovine) Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Pegaspargase. Approved Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Pegaspargase. Approved, Investigational Fingolimod Pegaspargase may increase the immunosuppressive activities of Fingolimod. Approved, Investigational G17DT The risk or severity of adverse effects can be increased when Pegaspargase is combined with G17DT. Investigational GI-5005 The risk or severity of adverse effects can be increased when Pegaspargase is combined with GI-5005. Investigational Gitoformate Gitoformate may decrease the cardiotoxic activities of Pegaspargase. Experimental Hepatitis A Vaccine The risk or severity of adverse effects can be increased when Pegaspargase is combined with Hepatitis A Vaccine. Approved Hepatitis B Vaccine (Recombinant) The risk or severity of adverse effects can be increased when Pegaspargase is combined with Hepatitis B Vaccine (Recombinant). Approved, Withdrawn Human rabies virus immune globulin The risk or severity of adverse effects can be increased when Pegaspargase is combined with Human rabies virus immune globulin. Approved INGN 201 The risk or severity of adverse effects can be increased when Pegaspargase is combined with INGN 201. Investigational INGN 225 The risk or severity of adverse effects can be increased when Pegaspargase is combined with INGN 225. Investigational Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pegaspargase is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated). Approved Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Pegaspargase. Experimental Leflunomide The risk or severity of adverse effects can be increased when Pegaspargase is combined with Leflunomide. Approved, Investigational Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Pegaspargase. Experimental Natalizumab The risk or severity of adverse effects can be increased when Pegaspargase is combined with Natalizumab. Approved, Investigational Ocrelizumab Ocrelizumab may increase the immunosuppressive activities of Pegaspargase. Approved, Investigational Oleandrin Oleandrin may decrease the cardiotoxic activities of Pegaspargase. Experimental, Investigational Ouabain Ouabain may decrease the cardiotoxic activities of Pegaspargase. Approved Paclitaxel The risk or severity of adverse effects can be increased when Paclitaxel is combined with Pegaspargase. Approved, Vet Approved Pegloticase The therapeutic efficacy of Pegaspargase can be decreased when used in combination with Pegloticase. Approved, Investigational Peruvoside Peruvoside may decrease the cardiotoxic activities of Pegaspargase. Experimental Pimecrolimus The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Pegaspargase. Approved, Investigational Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Pegaspargase. Experimental Rabies virus inactivated antigen, A The risk or severity of adverse effects can be increased when Pegaspargase is combined with Rabies virus inactivated antigen, A. Approved, Investigational Rabies virus inactivated antigen, A The therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Pegaspargase. Approved, Investigational Rindopepimut The risk or severity of adverse effects can be increased when Pegaspargase is combined with Rindopepimut. Investigational Roflumilast Roflumilast may increase the immunosuppressive activities of Pegaspargase. Approved Rotavirus Vaccine The risk or severity of adverse effects can be increased when Pegaspargase is combined with Rotavirus Vaccine. Approved Rubella virus vaccine The risk or severity of adverse effects can be increased when Pegaspargase is combined with Rubella virus vaccine. Approved, Investigational Salmonella typhi ty2 vi polysaccharide antigen The risk or severity of adverse effects can be increased when Pegaspargase is combined with Salmonella typhi ty2 vi polysaccharide antigen. Approved Salmonella typhi ty21a live antigen The risk or severity of adverse effects can be increased when Pegaspargase is combined with Salmonella typhi ty21a live antigen. Approved Sipuleucel-T The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Pegaspargase. Approved, Investigational SRP 299 The risk or severity of adverse effects can be increased when Pegaspargase is combined with SRP 299. Investigational Tacrolimus Tacrolimus may increase the immunosuppressive activities of Pegaspargase. Approved, Investigational Tecemotide The risk or severity of adverse effects can be increased when Pegaspargase is combined with Tecemotide. Investigational TG4010 The risk or severity of adverse effects can be increased when Pegaspargase is combined with TG4010. Investigational Tofacitinib Pegaspargase may increase the immunosuppressive activities of Tofacitinib. Approved, Investigational Trastuzumab Trastuzumab may increase the cardiotoxic activities of Pegaspargase. Approved, Investigational Varicella Zoster Vaccine (Live/Attenuated) The risk or severity of adverse effects can be increased when Pegaspargase is combined with Varicella Zoster Vaccine (Live/Attenuated). Approved Yellow Fever Vaccine The risk or severity of adverse effects can be increased when Pegaspargase is combined with Yellow Fever Vaccine. Approved, Investigational - Food Interactions
- Not Available
References
- General References
- Graham ML: Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev. 2003 Sep 26;55(10):1293-302. [PubMed:14499708]
- Link [Link]
- External Links
- UniProt
- P37595
- Genbank
- U00096
- PubChem Substance
- 46505366
- ChEMBL
- CHEMBL2108546
- PharmGKB
- PA164760860
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pegaspargase
- ATC Codes
- L01XX24 — Pegaspargase
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- FDA label
- Download (400 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Ben Venue Laboratories Inc.
- Enzon Inc.
- Dosage forms
Form Route Strength Injection, solution Intramuscular; Intravenous 750 [iU]/mL Liquid Intramuscular; Intravenous 750 unit Solution Intramuscular; Intravenous 750 unit Injection, solution 750 U/ml - Prices
Unit description Cost Unit Oncaspar 750 unit/ml vial 656.0USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source hydrophobicity 0.059 Not Available isoelectric point 4.67 Not Available
Taxonomy
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
Targets
1. L-asparagine
Yes
Other/unknown
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
- Douer D, Yampolsky H, Cohen LJ, Watkins K, Levine AM, Periclou AP, Avramis VI: Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia. Blood. 2007 Apr 1;109(7):2744-50. [PubMed:17132721]
- Wetzler M, Sanford BL, Kurtzberg J, DeOliveira D, Frankel SR, Powell BL, Kolitz JE, Bloomfield CD, Larson RA: Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. Blood. 2007 May 15;109(10):4164-7. Epub 2007 Jan 30. [PubMed:17264295]
- Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R: FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007 Aug;12(8):991-8. [PubMed:17766659]
Drug created on June 13, 2005 07:24 / Updated on April 23, 2018 22:56