Romiplostim

Identification

Summary

Romiplostim is a fusion protein thrombopoietin (TPO) peptide analog that increases platelet counts by binding to and activating the human TPO receptor. Used to treat thrombocytopenia associated with chronic immune thrombocytopenia (ITP).

Brand Names
Nplate
Generic Name
Romiplostim
DrugBank Accession Number
DB05332
Background

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.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Haematopoietic growth factors
Protein Chemical Formula
C2634H4086N722O790S18
Protein Average Weight
59000.0 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
  • Romiplostim
External IDs
  • AMG 531
  • AMG-531

Pharmacology

Indication

Treatment of chronic immune thrombocytopenic purpura.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
AThrombopoietin receptor
agonist
Humans
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 binding

Not Available

Metabolism
Not 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)

Clearance

Not Available

Adverse Effects
Adverseeffects
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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.

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
CyclophosphamideThe risk or severity of pulmonary toxicity can be increased when Romiplostim is combined with Cyclophosphamide.
VinblastineThe risk or severity of peripheral neuropathy can be increased when Romiplostim is combined with Vinblastine.
VincristineThe risk or severity of peripheral neuropathy can be increased when Romiplostim is combined with Vincristine.
VindesineThe risk or severity of peripheral neuropathy can be increased when Romiplostim is combined with Vindesine.
VinflunineThe risk or severity of peripheral neuropathy can be increased when Romiplostim is combined with Vinflunine.
VinorelbineThe risk or severity of peripheral neuropathy can be increased when Romiplostim is combined with Vinorelbine.
Interactions
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NplateInjection, powder, lyophilized, for solution250 ug/0.5mLSubcutaneousAMGEN INC2008-08-25Not applicableUS flag
NplateInjection, powder, for solution500 mcgSubcutaneousAmgen Europe B.V.2016-09-08Not applicableEU flag
NplateInjection, powder, for solution250 mcgSubcutaneousAmgen Europe B.V.2016-09-08Not applicableEU flag
NplatePowder, for solution250 mcg / vialSubcutaneousAmgen2009-04-15Not applicableCanada flag
NplateInjection, powder, for solution250 mcgSubcutaneousAmgen Europe B.V.2016-09-08Not applicableEU flag
NplateInjection, powder, for solution500 mcgSubcutaneousAmgen Europe B.V.2016-09-08Not applicableEU flag
NplateInjection, powder, lyophilized, for solution500 ug/1mLSubcutaneousAMGEN INC2008-08-25Not applicableUS flag
NplateInjection, powder, for solution250 mcgSubcutaneousAmgen Europe B.V.2016-09-08Not applicableEU flag
NplateInjection, powder, for solution125 mcgSubcutaneousAmgen Europe B.V.2020-12-16Not applicableEU flag
NplateInjection, powder, lyophilized, for solution125 ug/0.25mLSubcutaneousAMGEN INC2019-08-02Not applicableUS flag

Categories

ATC Codes
B02BX04 — Romiplostim
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
GN5XU2DXKV
CAS number
267639-76-9

References

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. [Article]
  2. Rice L: Drug evaluation: AMG-531 for the treatment of thrombocytopenias. Curr Opin Investig Drugs. 2006 Sep;7(9):834-41. [Article]
  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. [Article]
  4. Link [Link]
KEGG Drug
D08990
PubChem Substance
347910087
RxNav
805452
ChEMBL
CHEMBL1201832
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Romiplostim
FDA label
Download (232 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentIdiopathic Thrombocytopenic Purpura1
4CompletedTreatmentIdiopathic Thrombocytopenic Purpura / Thrombocytopenia1
3CompletedSupportive CareThrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura3
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura / Thrombocytopenia3
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura / Thrombocytopenia / Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) / Thrombocytopenic Purpura1
3CompletedTreatmentIdiopathic Thrombocytopenic Purpura / Thrombocytopenia / Thrombocytopenic Purpura2
3RecruitingTreatmentThrombocytopenia Chemotherapy Induced2
3WithdrawnTreatmentThrombocytopenia Chemotherapy Induced1
2Active Not RecruitingTreatmentIsolated Chemotherapy-induced Thrombocytopenia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionSubcutaneous125 MCG
Injection, powder, for solutionSubcutaneous250 MCG
Injection, powder, for solutionSubcutaneous500 MCG
Injection, powder, lyophilized, for solutionSubcutaneous125 ug/0.25mL
Injection, powder, lyophilized, for solutionSubcutaneous250 ug/0.5mL
Injection, powder, lyophilized, for solutionSubcutaneous500 ug/1mL
Powder, for solutionSubcutaneous250 mcg / vial
Powder, for solutionSubcutaneous500 mcg / vial
Injection, powder, lyophilized, for solutionSubcutaneous625 mcg
Injection, powder, lyophilized, for solutionSubcutaneous250 mcg
Injection, powder, for solutionSubcutaneous250 mcg/1vial
Injection, powder, for solutionSubcutaneous
Injection, powder, for solutionSubcutaneous250 mcg/0.5ml
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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. [Article]

Drug created on November 18, 2007 18:23 / Updated on October 24, 2021 16:00