Idarucizumab

Identification

Summary

Idarucizumab is an antibody that binds dabigatran for the reversal of anticoagulant effects of dabigatran.

Brand Names
Praxbind
Generic Name
Idarucizumab
DrugBank Accession Number
DB09264
Background

Idarucizumab is a humanized monoclonal antibody fragment (Fab) derived from an immunoglobulin G1 isotype molecule that binds to and inactivates the oral anticoagulant dabigatran, thereby reversing its anticoagulant effect. As a direct acting oral anticoagulant (DOAC), one of the risks associated with the use of dabigatran includes bleeding, espeically when given to patients at increased risk (elderly, chronic kidney disease, concomitant NSAID or warfarin use, etc).

Approved under the tradename Praxbind (FDA), idarucizumab is indicated for the emergency treatment of dabigatran-associated bleeding in life-threatening or surgically induced situations. Its use is associated with immediate, complete and sustained reversal of the anticoagulant effects of dabigatran.

Idarucizumab protein structure can be viewed below, with disulfide bridges at the following points: H22-H95, H149-H205, H225-L-219, L23-L93, L139-L199.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Db09264
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
>Heavy Chain
QVQLQESGPGLVKPSETLSLTCTVSGFSLTSYIVDWIRQPPGKGLEWIGVIWAGGSTGYN
SALRSRVSITKDTSKNQFSLKLSSVTAADTAVYYCASAAYYSYYNYDGFAYWGQGTLVTV
SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ
SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSC
>Light Chain
DVVMTQSPLSLPVTLGQPASISCKSSQSLLYTDGKTYLYWFLQRPGQSPRRLIYLVSKLD
SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCLQSTHFPHTFGGGTKVEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
  • aDabi-Fab
  • Idarucizumab
External IDs
  • BI 655075
  • BI-655075
  • BI655075

Pharmacology

Indication

For use in patients treated with Dabigatran when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures and in life-threatening or uncontrolled bleeding.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Not Available

Mechanism of action

Idarucizumab is a specific reversal agent for dabigatran. It is a humanized monoclonal antibody fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect.

Absorption

Not Available

Volume of distribution

8.9 L

Protein binding

Not Available

Metabolism

Several pathways have been described that may contribute to the metabolism of antibodies. All of these pathways involve biodegradation of the antibody to smaller molecules, i.e., small peptides or amino acids which are then reabsorbed and incorporated in the general protein synthesis.

Route of elimination

After intravenous administration of 5 g idarucizumab, 32.1% (gCV 60.0%) of the dose was recovered in urine within a collection period of 6 hours and less than 1% in the following 18 hours. The remaining part of the dose is assumed to be eliminated via protein catabolism, mainly in the kidney.

Half-life

initial half-life: 47 minutes terminal half-life: 10.3 h

Clearance

47.0 mL/min

Adverse Effects
Adverseeffects
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Toxicity

In healthy volunteers, the most frequently reported adverse reactions in greater than or equal to 5% of subjects treated with idarucizumab was headache. In patients, the most frequently reported adverse reactions in greater than or equal to 5% of patients treated with idarucizumab were hypokalemia, delirium, constipation, pyrexia, and pneumonia.

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
AbacavirAbacavir may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Idarucizumab.
AceclofenacAceclofenac may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Idarucizumab which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AcrivastineIdarucizumab may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PraxbindInjection, solution2.5 g/50mLIntravenousBoehringer Ingelheim2016-09-08Not applicableEU flag
PraxbindInjection50 mg/1mLIntravenousBoehringer Ingelheim Pharmaceuticals, Inc.2015-10-21Not applicableUS flag
PraxbindSolution50 mg / mLIntravenousBoehringer Ingelheim (Canada) Ltd Ltee2016-05-24Not applicableCanada flag

Categories

ATC Codes
V03AB37 — Idarucizumab
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
97RWB5S1U6
CAS number
1362509-93-0

References

General References
  1. Syed YY: Idarucizumab: A Review as a Reversal Agent for Dabigatran. Am J Cardiovasc Drugs. 2016 Aug;16(4):297-304. doi: 10.1007/s40256-016-0181-4. [Article]
  2. Yogaratnam D, Ditch K, Medeiros K, Doyno C, Fong JJ: Idarucizumab for Reversal of Dabigatran. Ann Pharmacother. 2016 Jul 7. pii: 1060028016659504. [Article]
KEGG Drug
D10741
PubChem Substance
347910427
RxNav
1716191
RxList
RxList Drug Page
Wikipedia
Idarucizumab
FDA label
Download (227 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentHemorrhage4
1CompletedTreatmentHealthy Subjects (HS)3
1CompletedTreatmentHemorrhage1
Not AvailableCompletedNot AvailableThromboembolism1
Not AvailableRecruitingNot AvailableIntracranial Hemorrhages1
Not AvailableWithdrawnNot AvailableHemorrhage1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous
InjectionIntravenous50 mg/1mL
SolutionIntravenous50 mg / mL
Injection, solutionIntravenous
Solution, concentrateIntravenous50 mg
Injection, solutionIntravenous2.5 g/50ml
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Drug created on October 27, 2015 18:45 / Updated on September 19, 2021 19:53