Identification

Name
Pegaspargase
Accession Number
DB00059
Description

Pegylated L-asparagine amidohydrolase from E. coli. Pegylation substantially (by a factor of 4) extends the protein half life.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
Protein Structure
Db00059
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
  • Pegaspargasa

Pharmacology

Indication

For treatment of acute lymphoblastic leukemia

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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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.

TargetActionsOrganism
AL-asparagine
other/unknown
Humans
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
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
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
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Pegaspargase is combined with Abatacept.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Pegaspargase.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Pegaspargase.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Pegaspargase.
AlefaceptThe risk or severity of adverse effects can be increased when Pegaspargase is combined with Alefacept.
AlemtuzumabThe risk or severity of adverse effects can be increased when Pegaspargase is combined with Alemtuzumab.
AllantoinThe therapeutic efficacy of Allantoin can be increased when used in combination with Pegaspargase.
AltretamineThe risk or severity of adverse effects can be increased when Pegaspargase is combined with Altretamine.
AmsacrineThe risk or severity of adverse effects can be increased when Pegaspargase is combined with Amsacrine.
AnakinraThe risk or severity of adverse effects can be increased when Anakinra is combined with Pegaspargase.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Lyophilized PegaspargaseInjection, powder, lyophilized, for solution750 U/1mLIntramuscularBaxalta US Inc.2018-02-072020-05-16Us
OncasparLiquidIntramuscular; IntravenousAventis Pharma Ltd.1998-10-132004-01-02Canada
OncasparSolutionIntramuscular; IntravenousServier2017-06-01Not applicableCanada
OncasparInjection, solution750 [iU]/1mLIntramuscular; IntravenousSigma Tau Pharmaceuticals, Inc.1994-02-012016-11-30Us
OncasparInjection, solution750 [iU]/1mLIntramuscular; IntravenousBaxalta US Inc.1994-02-012020-05-16Us
OncasparInjection, solution750 U/mlBaxalta Innovations Gmb H2016-01-14Not applicableEu
OncasparInjection, solution750 [iU]/1mLIntramuscular; IntravenousServier Pharmaceuticals LLC2020-01-02Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01XX24 — Pegaspargase
Drug Categories
Chemical TaxonomyProvided by Classyfire
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

Chemical Identifiers

UNII
7D96IR0PPM
CAS number
130167-69-0

References

General References
  1. Graham ML: Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev. 2003 Sep 26;55(10):1293-302. [PubMed:14499708]
UniProt
P37595
Genbank
U00096
PubChem Substance
46505366
RxNav
34132
ChEMBL
CHEMBL2108546
PharmGKB
PA164760860
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pegaspargase
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (400 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentHematological Neoplasms1
4RecruitingTreatmentNasal and Nasal-type NK/T-cell Lymphoma1
4Unknown StatusTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)2
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Undifferentiated Leukemia (AUL) / Childhood T Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Adult B Lymphoblastic Lymphoma / Ann Arbor Stage I B Lymphoblastic Lymphoma / Ann Arbor Stage II B Lymphoblastic Lymphoma / Childhood B Acute Lymphoblastic Leukemia / Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / Childhood B Lymphoblastic Lymphoma / Down Syndrome (DS) / Hypodiploid B Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative1
3Active Not RecruitingTreatmentAdult T Acute Lymphoblastic Leukemia / Ann Arbor Stage II Adult Lymphoblastic Lymphoma / Ann Arbor Stage II Childhood Lymphoblastic Lymphoma / Ann Arbor Stage III Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Childhood Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult Lymphoblastic Lymphoma / Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma / Childhood T Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentB Acute Lymphoblastic Leukemia / Central Nervous System Leukemia / Ph-Like Acute Lymphoblastic Leukemia / Testicular Leukemia1
3Active Not RecruitingTreatmentB-cell Childhood Acute Lymphoblastic Leukemia / Intermediate Risk Recurrent Childhood Acute Lymphoblastic Leukemia / L1 Childhood Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Ben Venue Laboratories Inc.
  • Enzon Inc.
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntramuscular750 U/1mL
Injection, solution750 U/ml
Injection, solutionIntramuscular; Intravenous750 [iU]/1mL
LiquidIntramuscular; Intravenous
SolutionIntramuscular; Intravenous
Prices
Unit descriptionCostUnit
Oncaspar 750 unit/ml vial656.0USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity0.059Not Available
isoelectric point4.67Not Available

Targets

Kind
Small molecule
Organism
Humans
Pharmacological action
Yes
Actions
Other/unknown
References
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da

Drug created on June 13, 2005 07:24 / Updated on August 02, 2020 22:18

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