You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameRomiplostim
Accession NumberDB05332
TypeBiotech
GroupsApproved
DescriptionRomiplostim is a thrombopoiesis stimulating dimer Fc-peptide fusion protein (peptibody) to increase platelet production through activation of the thrombopoietin receptor. The peptibody molecule has two identical single-chain subunits, each one is made up of 269 amino acid residues. Each subunit consists of an IgG1 Fc carrier domain that is covalently attached to a polypeptide sequence that contains two binding domains to interact with thrombopoietin receptor c-Mpl. Each domain consists of 14 amino acids. Interestingly, romiplostim's amino acid sequence is not similar to that of endogenous thrombopoietin. Romiplostim is produced by recombinant DNA technology in Escherichia coli. FDA approved on August 22, 2008.
Protein structureNo structure small
Related Articles
Protein chemical formulaC2634H4086N722O790S18
Protein average weight59000.0 Da
Sequences
>Thrombopoietin receptor binding domain amino acid sequence 
IEGPTLRQWLAARA
>Amino acid sequence for Fc fusion compound
MDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGGIEGPTLR
QWLAARAGGGGGGGGIEGPTLRQWLAARA
Download FASTA Format
Synonyms
Semaxanib
Semaxinib
SU-5416
External Identifiers
  • AMG 531
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NplatePowder for solution for injection500 μgSubcutaneous useAmgen Europe B.V.2009-02-04Not applicableEu
Nplateinjection, powder, lyophilized, for solution250 ug/.5mLsubcutaneousAmgen Inc2008-08-25Not applicableUs
NplatePowder and solvent for solution for injection500 μgSubcutaneous use 1Amgen Europe B.V.2009-02-04Not applicableEu
NplatePowder for solution for injection250 μgSubcutaneous useAmgen Europe B.V.2009-02-04Not applicableEu
NplatePowder and solvent for solution for injection250 μgSubcutaneous useAmgen Europe B.V.2009-02-04Not applicableEu
Nplateinjection, powder, lyophilized, for solution500 ug/mLsubcutaneousAmgen Inc2008-08-25Not applicableUs
NplatePowder for solution for injection500 μgSubcutaneous useAmgen Europe B.V.2009-02-04Not applicableEu
NplatePowder and solvent for solution for injection250 μgSubcutaneous useAmgen Europe B.V.2009-02-04Not applicableEu
Nplatepowder for solution250 mcgsubcutaneousAmgen Canada Inc2009-04-15Not applicableCanada
NplatePowder for solution for injection250 μgSubcutaneous useAmgen Europe B.V.2009-02-04Not applicableEu
NplatePowder and solvent for solution for injection500 μgSubcutaneous useAmgen Europe B.V.2009-02-04Not applicableEu
Nplatepowder for solution500 mcgsubcutaneousAmgen Canada Inc2009-04-15Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIGN5XU2DXKV
CAS number267639-76-9
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationTreatment of chronic immune thrombocytopenic purpura.
PharmacodynamicsResponses to platelet increase varies between patients thus indicating a need for individualization of dose. However, a dose dependent-increase in platelet counts have been observed in clinical trials. Does not affect platelet destruction.
Mechanism of actionRomiplostim is a thrombopoietin receptor agonist that activates intracellular transcriptional pathways via c-Mpl to increase production of platelets. It also works similarly to thrombopoietin (TPO), an endogenous glycoprotein hormone that regulates the production of platelets in the bone marrow.
Related Articles
AbsorptionCmax, healthy volunteers, subQ = 24-36 hours; Cmax, immune thrombocytopenia patients, subQ = 7-50 hours (median = 14 hours). Not affected by age, weight, or gender. Accumulation does not occur after six weekly doses of 3 mcg/kg romiplostim.
Volume of distribution

In healthy volunteers, non-linear decrease in Vd with increase IV dose of romiplostim which indicates saturation of c-Mpl receptors.
Vd, 0.3 μg/kg = 122 mL/kg
Vd, 10 μg/kg = 48.2 mL/kg

Protein bindingNot Available
MetabolismNot Available
Route of eliminationRenal clearance (more dominant mode of clearance as dose increases) and binding to c-Mpl receptors (dominant mode of clearance at low doses)
Half lifeImmune thrombocytopenia patients, subQ = 3.5 days (median) (range 1-34 days)
ClearanceNot Available
ToxicityThe most common adverse reactions (≥ 5% higher patient incidence in Nplate versus placebo) are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, and paresthesia. Headache was the most commonly reported adverse reaction that did not occur at ≥ 5% higher patient incidence in Nplate versus placebo. LD50 = 980 mg/kg.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionsubcutaneous250 ug/.5mL
Injection, powder, lyophilized, for solutionsubcutaneous500 ug/mL
Powder and solvent for solution for injectionSubcutaneous use250 μg
Powder and solvent for solution for injectionSubcutaneous use500 μg
Powder and solvent for solution for injectionSubcutaneous use 1500 μg
Powder for solutionsubcutaneous250 mcg
Powder for solutionsubcutaneous500 mcg
Powder for solution for injectionSubcutaneous use250 μg
Powder for solution for injectionSubcutaneous use500 μg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
References
Synthesis ReferenceNot Available
General References
  1. Kumagai Y, Fujita T, Ozaki M, Sahashi K, Ohkura M, Ohtsu T, Arai Y, Sonehara Y, Nichol JL: Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. J Clin Pharmacol. 2007 Dec;47(12):1489-97. Epub 2007 Oct 9. [PubMed:17925591 ]
  2. Rice L: Drug evaluation: AMG-531 for the treatment of thrombocytopenias. Curr Opin Investig Drugs. 2006 Sep;7(9):834-41. [PubMed:17002262 ]
  3. Keating GM: Romiplostim: a review of its use in immune thrombocytopenia. Drugs. 2012 Feb 12;72(3):415-35. doi: 10.2165/11208260-000000000-00000. [PubMed:22316355 ]
  4. Link [Link]
External Links
ATC CodesB02BX04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (232 KB)
MSDSDownload (479 KB)
Interactions
Drug Interactions
Drug
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Romiplostim.
BevacizumabBevacizumab may increase the cardiotoxic activities of Romiplostim.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Romiplostim.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Romiplostim.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Romiplostim.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Romiplostim.
DigoxinDigoxin may decrease the cardiotoxic activities of Romiplostim.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Romiplostim.
OuabainOuabain may decrease the cardiotoxic activities of Romiplostim.
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Romiplostim.
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Romiplostim.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Transmembrane signaling receptor activity
Specific Function:
Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.
Gene Name:
MPL
Uniprot ID:
P40238
Molecular Weight:
71244.08 Da
References
  1. Krzyzanski W, Sutjandra L, Perez-Ruixo JJ, Sloey B, Chow AT, Wang YM: Pharmacokinetic and pharmacodynamic modeling of romiplostim in animals. Pharm Res. 2013 Mar;30(3):655-69. doi: 10.1007/s11095-012-0894-2. Epub 2012 Dec 19. [PubMed:23250851 ]
Comments
comments powered by Disqus
Drug created on November 18, 2007 11:23 / Updated on August 17, 2016 12:24