Idarucizumab

Identification

Name
Idarucizumab
Accession Number
DB09264
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

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.

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
External IDs
BI 655075 / BI-655075 / BI655075
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PraxbindInjection, solution2.5 g/50mLIntravenousBoehringer Ingelheim2015-11-20Not applicableEu
PraxbindInjection50 mg/1mLIntravenousBoehringer Ingelheim2015-10-21Not applicableUs
PraxbindSolution50 mgIntravenousBoehringer Ingelheim (Canada) Ltd Ltee2016-05-24Not applicableCanada
Categories
UNII
97RWB5S1U6
CAS number
1362509-93-0

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.

Associated Conditions
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.

TargetActionsOrganism
ADabigatran etexilate
antibody
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

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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Idarucizumab.
AcetaminophenAcetaminophen may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Idarucizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Idarucizumab.
AlprazolamAlprazolam may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AmilorideAmiloride may increase the excretion rate of Idarucizumab which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineIdarucizumab may decrease the excretion rate of Amitriptyline which could result in a higher serum level.
AmlodipineAmlodipine may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
AmoxicillinAmoxicillin may decrease the excretion rate of Idarucizumab which could result in a higher serum level.
Food Interactions
Not Available

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. [PubMed:27388764]
  2. Yogaratnam D, Ditch K, Medeiros K, Doyno C, Fong JJ: Idarucizumab for Reversal of Dabigatran. Ann Pharmacother. 2016 Jul 7. pii: 1060028016659504. [PubMed:27389324]
External Links
KEGG Drug
D10741
PubChem Substance
347910427
RxList
RxList Drug Page
Wikipedia
Idarucizumab
ATC Codes
V03AB37 — Idarucizumab
AHFS Codes
  • 20:28.92 — Antihemorrhagic Agents, Miscellaneous
FDA label
Download (227 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHemorrhage1
3CompletedTreatmentHemorrhage2
3RecruitingTreatmentHemorrhage1
3RecruitingTreatmentNonvalvular Atrial Fibrillation1
Not AvailableNot Yet RecruitingNot AvailableEmergency Procedures / Uncontrolled Hemorrhage1
Not AvailableNot Yet RecruitingNot AvailableThromboembolism1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous50 mg/1mL
Injection, solutionIntravenous2.5 g/50mL
SolutionIntravenous50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Small molecule
Organism
Not Available
Pharmacological action
Yes
Actions
Antibody
References
  1. Yogaratnam D, Ditch K, Medeiros K, Doyno C, Fong JJ: Idarucizumab for Reversal of Dabigatran. Ann Pharmacother. 2016 Jul 7. pii: 1060028016659504. [PubMed:27389324]

Drug created on October 27, 2015 12:45 / Updated on September 20, 2018 21:34