Panitumumab

Identification

Summary

Panitumumab is a recombinant humanized monoclonal antibody used to treat EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.

Brand Names
Vectibix
Generic Name
Panitumumab
DrugBank Accession Number
DB01269
Background

Panitumumab (ABX-EGF) is a recombinant human IgG2 monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). This drug is an antineoplastic agent.

Panitumumab was granted FDA approval on 27 September 2006.6

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • ABX-EGF
  • Panitumumab
External IDs
  • E7.6.3

Pharmacology

Indication

For the treatment of EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMetastatic colorectal cancer••••••••••••••••••••••• ••••• ••••••••• •••• ••••••••••••••••• ••••••••••• ••• ••••••••••
Used in combination to treatMetastatic colorectal cancerRegimen in combination with: Oxaliplatin (DB00526), Fluorouracil (DB00544), Leucovorin (DB00650)••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases. Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. Interaction of EGFR with its normal ligands causes phosphorylation and activation of a series of intracellular proteins that will in turn regulate the transcription of genes involved with cellular growth and survival, motility, and prolieration. Signal transduction through EGFR leads to the activation of the wild type KRAS gene, but the presence of an activating somatic mutation of the KRAS gene within a cancer cell can result in the dysregulation of signaling pathways and resistance to EGFR inhibitor therapy.

Mechanism of action

Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR.

TargetActionsOrganism
AEpidermal growth factor receptor
suppressor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

7.5 days (range: 4-11 days)

Clearance
  • 4.9+/- 1.4 mL/kg/day [Following single-dose administrations of panitumumab as 1-hour infusions]
Adverse Effects
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Toxicity

Panitumumab was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving panitumumab. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported.

Pathways
PathwayCategory
Panitumumab Action PathwayDrug action
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Panitumumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Panitumumab.
AducanumabThe risk or severity of adverse effects can be increased when Panitumumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Panitumumab.
AlirocumabThe risk or severity of adverse effects can be increased when Panitumumab is combined with Alirocumab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VectibixSolution200 mg / 10 mLIntravenousAmgenNot applicableNot applicableCanada flag
VectibixSolution100 mg/5mLIntravenousAMGEN INC2006-10-10Not applicableUS flag
VectibixInjection, solution, concentrate20 mg/mlIntravenousAmgen Europe B.V.2016-09-20Not applicableEU flag
VectibixSolution100 mg / 5 mLIntravenousAmgen2008-05-27Not applicableCanada flag
VectibixInjection200 mg/10mLIntravenousAmgen Inc.2008-07-162008-07-16US flag

Categories

ATC Codes
L01FE02 — Panitumumab
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
6A901E312A
CAS number
339177-26-3

References

General References
  1. Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, Rowinsky EK, Dutcher JP, Vogelzang NJ, Gollub J, Thompson JA, Schwartz G, Bukowski RM, Roskos LK, Schwab GM: Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):984-90. [Article]
  2. Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001 Apr;38(1):17-23. [Article]
  3. Wu M, Rivkin A, Pham T: Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther. 2008 Jan;30(1):14-30. doi: 10.1016/j.clinthera.2008.01.014. [Article]
  4. Saadeh CE, Lee HS: Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer. Ann Pharmacother. 2007 Apr;41(4):606-13. Epub 2007 Mar 13. [Article]
  5. Keating GM: Panitumumab: a review of its use in metastatic colorectal cancer. Drugs. 2010 May 28;70(8):1059-78. doi: 10.2165/11205090-000000000-00000. [Article]
  6. FDA Approved Drug Products: VECTIBIX (panitumumab) Injection for intravenous use [Link]
UniProt
P01859
PubChem Substance
46505063
RxNav
263034
ChEMBL
CHEMBL1201827
Therapeutic Targets Database
DNC000135
PharmGKB
PA162373091
Drugs.com
Drugs.com Drug Page
Wikipedia
Panitumumab

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4TerminatedHealth Services ResearchColon Cancer / Unresectable Metastasis Originating in Colonic Cancer1
4Unknown StatusTreatmentCancer1
3Active Not RecruitingTreatmentColorectal Cancer2
3CompletedBasic ScienceStage III Colon Cancer1
3CompletedTreatmentColorectal Cancer3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amgen Inc.
Dosage Forms
FormRouteStrength
InjectionIntravenous200 mg/10mL
Injection, solution, concentrateIntravenous20 mg/ml
Injection, solution, concentrateIntravenous; Parenteral20 MG/ML
SolutionIntravenous100 mg / 5 mL
SolutionIntravenous100 mg/5mL
SolutionIntravenous200 mg / 10 mL
SolutionIntravenous400 mg / 20 mL
SolutionIntravenous400 mg/20mL
SolutionParenteral400.000 mg
Injection, solutionIntravenous
Injection, solutionIntravenous20 mg/mL
SolutionIntravenous100 mg
Solution, concentrateIntravenous20 mg
Injection, solution, concentrateIntravenous100 mg/5ml
Prices
Unit descriptionCostUnit
Vectibix 400 mg/20ml Solution 20ml Vial4349.4USD vial
Vectibix 100 mg/5ml Solution 5ml Vial1059.24USD vial
Vectibix 100 mg/5 ml vial203.7USD ml
Vectibix 200 mg/10 ml vial203.7USD ml
Vectibix 400 mg/20 ml vial203.7USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Suppressor
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
References
  1. Lynch DH, Yang XD: Therapeutic potential of ABX-EGF: a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment. Semin Oncol. 2002 Feb;29(1 Suppl 4):47-50. [Article]
  2. Cohen RB: Epidermal growth factor receptor as a therapeutic target in colorectal cancer. Clin Colorectal Cancer. 2003 Feb;2(4):246-51. [Article]
  3. Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, Rowinsky EK, Dutcher JP, Vogelzang NJ, Gollub J, Thompson JA, Schwartz G, Bukowski RM, Roskos LK, Schwab GM: Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):984-90. [Article]
  4. Segaert S, Van Cutsem E: Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005 Sep;16(9):1425-33. Epub 2005 Jul 12. [Article]
  5. Heymach JV, Nilsson M, Blumenschein G, Papadimitrakopoulou V, Herbst R: Epidermal growth factor receptor inhibitors in development for the treatment of non-small cell lung cancer. Clin Cancer Res. 2006 Jul 15;12(14 Pt 2):4441s-4445s. [Article]
  6. Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001 Apr;38(1):17-23. [Article]
  7. Keating GM: Spotlight on panitumumab in metastatic colorectal cancer. BioDrugs. 2010 Aug 1;24(4):275-8. doi: 10.2165/11205460-000000000-00000. [Article]
  8. Wu M, Rivkin A, Pham T: Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther. 2008 Jan;30(1):14-30. doi: 10.1016/j.clinthera.2008.01.014. [Article]
  9. Saadeh CE, Lee HS: Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer. Ann Pharmacother. 2007 Apr;41(4):606-13. Epub 2007 Mar 13. [Article]
  10. Jean GW, Shah SR: Epidermal growth factor receptor monoclonal antibodies for the treatment of metastatic colorectal cancer. Pharmacotherapy. 2008 Jun;28(6):742-54. doi: 10.1592/phco.28.6.742. [Article]
  11. Keating GM: Panitumumab: a review of its use in metastatic colorectal cancer. Drugs. 2010 May 28;70(8):1059-78. doi: 10.2165/11205090-000000000-00000. [Article]
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created at May 16, 2007 20:12 / Updated at June 03, 2022 07:24