Identification
NameRomiplostim
Accession NumberDB05332
TypeBiotech
GroupsApproved
Description

Romiplostim 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
SynonymsNot Available
External IDs AMG 531 / AMG-531
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NplatePowder, for solution250 mcgSubcutaneousAmgen2009-04-15Not applicableCanada
NplateInjection, powder, for solution500 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution500 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, lyophilized, for solution500 ug/mLSubcutaneousAmgen2008-08-25Not applicableUs
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution500 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplatePowder, for solution500 mcgSubcutaneousAmgen2009-04-15Not applicableCanada
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, lyophilized, for solution250 ug/.5mLSubcutaneousAmgen2008-08-25Not applicableUs
NplateInjection, powder, for solution250 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
NplateInjection, powder, for solution500 μgSubcutaneousAmgen Europe B.V.2009-02-04Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIGN5XU2DXKV
CAS number267639-76-9
Pharmacology
Indication

Treatment of chronic immune thrombocytopenic purpura.

Structured Indications
Pharmacodynamics

Responses 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 action

Romiplostim 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Thrombopoietin receptorProteinyes
agonist
HumanP40238 details
Related Articles
Absorption

Cmax, 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 elimination

Renal clearance (more dominant mode of clearance as dose increases) and
binding to c-Mpl receptors (dominant mode of clearance at low doses)

Half life

Immune thrombocytopenia patients, subQ = 3.5 days (median) (range 1-34 days)

ClearanceNot Available
Toxicity

The 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
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Romiplostim.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Romiplostim.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Romiplostim.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Romiplostim.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Romiplostim.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Romiplostim.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Romiplostim.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Romiplostim.Approved, Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Romiplostim.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Romiplostim.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Romiplostim.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Romiplostim.Approved, Investigational
Food InteractionsNot 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 — Romiplostim
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (232 KB)
MSDSDownload (479 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingSupportive CareMalignancies, Hematologic1
1, 2Active Not RecruitingTreatmentPersistent Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)1
1, 2CompletedPreventionCancer, Advanced / Tumors, Solid1
1, 2CompletedSupportive CareCancers / Chemotherapy-Induced Thrombocytopenia / Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL) / Oncology / Thrombocytopenias1
1, 2CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)1
1, 2CompletedTreatmentMalignant Lymphomas1
1, 2CompletedTreatmentThrombocytopenic Purpura1
1, 2RecruitingTreatmentImmune Thrombocytopenia (ITP)1
2CompletedSupportive CareCancers / Chemotherapy-Induced Thrombocytopenia / Lung Cancers / Neoplasms, Lung / Non-Small-Cell Lung Carcinoma (NSCLC) / Oncology / Thrombocytopenias / Tumors, Solid1
2CompletedSupportive CareMyelodysplastic Syndromes / Smith-Magenis Syndrome / Thrombocytopenias2
2CompletedSupportive CareMyelodysplastic Syndromes / Thrombocytopenias1
2CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP)2
2CompletedTreatmentMyelodysplastic Syndromes / Refractory Cytopenias / Smith-Magenis Syndrome / Thrombocytopenias1
2CompletedTreatmentThrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)1
2RecruitingTreatmentGlioblastomas / Thrombocytopenias1
2RecruitingTreatmentIsolated Chemotherapy-induced Thrombocytopenia1
2RecruitingTreatmentMyelodysplastic Syndromes1
2TerminatedSupportive CareRefractory Multiple Myeloma / Stage I Multiple Myeloma / Stage II Multiple Myeloma / Stage III Multiple Myeloma / Thrombocytopenias1
2TerminatedTreatmentHepatitis C Infection / Thrombocytopenias1
2Unknown StatusPreventionNon-Hodgkin's Lymphoma (NHL)1
2Unknown StatusTreatmentImmune Thrombocytopenia1
2, 3Active Not RecruitingTreatmentAplastic Anaemia (AA)1
2, 3CompletedTreatmentThrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)1
3Active Not RecruitingTreatmentImmune Thrombocytopenia / Immune Thrombocytopenia (ITP)1
3CompletedSupportive CareThrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Pediatric Subjects With Immune Idiopathic Thrombocytopenic Purpura ITP1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP)1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Immune Thrombocytopenia / Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenias / Thrombocytopenic Purpura1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenias / Thrombocytopenic Purpura1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenias3
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenias / Thrombocytopenic Purpura1
3CompletedTreatmentImmune Thrombocytopenia1
4CompletedTreatmentIdiopathic Thrombocytopenic Purpura (ITP) / Thrombocytopenias1
4RecruitingTreatmentImmune Thrombocytopenia1
Not AvailableCompletedNot AvailableImmune Thrombocytopenia1
Not AvailableCompletedNot AvailableImmune Thrombocytopenic Purpura ( ITP )1
Not AvailableCompletedNot AvailableThrombocytopenias1
Not AvailableCompletedTreatmentHematology / Myelodysplastic Syndromes / Smith-Magenis Syndrome / Thrombocytopenias1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous250 μg
Injection, powder, for solutionSubcutaneous500 μg
Injection, powder, lyophilized, for solutionSubcutaneous250 ug/.5mL
Injection, powder, lyophilized, for solutionSubcutaneous500 ug/mL
Powder, for solutionSubcutaneous250 mcg
Powder, for solutionSubcutaneous500 mcg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
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

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
Uniprot Name:
Thrombopoietin receptor
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 ]
Drug created on November 18, 2007 11:23 / Updated on June 05, 2017 16:36