Pegaspargase

Identification

Summary

Pegaspargase is a modified form of L-asparagine amidohydrolase used to treat acute lymphoblastic leukemia, which is dependent on an external source of asparagine.

Brand Names
Oncaspar
Generic Name
Pegaspargase
DrugBank Accession Number
DB00059
Background

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
  • Pegaspargase

Pharmacology

Indication

For treatment of acute lymphoblastic leukemia

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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
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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.

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.
Interactions
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Food Interactions
  • Avoid excessive or chronic alcohol consumption. Alcohol and pegaspargase can both cause hepatoxicity, therefore if they are used together they may have additive hepatoxic effects.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Lyophilized PegaspargaseInjection, powder, lyophilized, for solution750 U/1mLIntramuscularBaxalta US Inc.2018-02-072020-05-16US flag
Lyophilized PegaspargaseInjection, powder, lyophilized, for solution750 [iU]/1mLIntravenousServier Pharmaceuticals2020-08-03Not applicableUS flag
Oncaspar750 U/mlLes Laboratoires Servier2020-12-16Not applicableEU flag
OncasparLiquid750 unit / mLIntramuscular; IntravenousAventis Pharma Ltd.1998-10-132004-01-02Canada flag
OncasparInjection, solution750 U/mlIntramuscular; IntravenousLes Laboratoires Servier2016-09-08Not applicableEU flag
OncasparInjection, solution750 [iU]/1mLIntramuscular; IntravenousServier Pharmaceuticals LLC2020-01-02Not applicableUS flag
OncasparInjection, solution750 [iU]/1mLIntramuscular; IntravenousSigma Tau Pharmaceuticals, Inc.1994-02-012016-11-30US flag
OncasparSolution750 unit / mLIntramuscular; IntravenousServier2017-06-01Not applicableCanada flag
OncasparInjection, solution750 [iU]/1mLIntramuscular; IntravenousBaxalta US Inc.1994-02-012020-05-16US flag

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
Affected organisms
  • Humans and other mammals

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. [Article]
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
4Unknown StatusTreatmentAcute Lymphoblastic Leukaemias (ALL)1
4Unknown StatusTreatmentNasal and Nasal-type NK/T-cell Lymphoma1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)2
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Undifferentiated Leukemia (AUL) / Childhood T 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 RecruitingTreatmentExtranodal NK/T-cell Lymphoma, Nasal Type1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Ben Venue Laboratories Inc.
  • Enzon Inc.
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntramuscular750 U/1mL
Injection, powder, lyophilized, for solutionIntravenous750 [iU]/1mL
Injection, powder, for solutionIntramuscular; Intravenous
Injection, solutionIntramuscular; Intravenous
Injection, solutionIntramuscular; Intravenous750 [iU]/1mL
Injection, solutionIntramuscular; Intravenous750 U/ml
LiquidIntramuscular; Intravenous750 unit / mL
SolutionIntramuscular; Intravenous750 unit / mL
SolutionIntramuscular; Intravenous750 IU
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

Drugtargets
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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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

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 13:24 / Updated on June 23, 2021 06:08