Praxbind (idarucizumab)

Anticoagulant Reversal Agent for Dabigatran Intravenous Vial (Ml)

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Last reviewed · Source: First Databank (FDB) drug data

Overview

Idarucizumab, a recombinant humanized monoclonal antibody fragment, is a specific reversal agent for the anticoagulant effects of dabigatran.

Idarucizumab is a recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody fragment that binds specifically to unbound and thrombin-bound dabigatran and its acylglucuronide metabolites, rapidly forming stable and essentially irreversible complexes. The drug is prepared from cultures of genetically modified mammalian (Chinese hamster ovary) cells using recombinant DNA technology. The affinity of idarucizumab for dabigatran is approximately 350-fold greater than that of dabigatran for thrombin.

Because of the high affinity of idarucizumab for dabigatran, thrombin is no longer inhibited by dabigatran after idarucizumab administration and can regain its ability to trigger clotting. Idarucizumab has been shown to reverse the anticoagulant effects of dabigatran within minutes after administration. Idarucizumab is found mainly in plasma after administration whereas dabigatran is capable of moving freely between the blood and extravascular compartments.

The concentration of unbound dabigatran (i.e., dabigatran and its conjugates that are not bound to plasma proteins or to idarucizumab) decreases when idarucizumab binds dabigatran in plasma. Any residual unbound dabigatran reestablishes equilibrium by moving from the extravascular compartment into plasma where it is bound by idarucizumab, provided that idarucizumab is administered in excess. This process continues until all of the dabigatran is bound and its anticoagulant activity is neutralized.

Increases in plasma dabigatran concentrations as well as elevated coagulation parameters (e.g., activated partial thromboplastin time (aPTT), ecarin clotting time (ECT)) were seen in a limited number of patients in the RE-VERSE AD trial 12-24 hours after administration of idarucizumab; this finding is most likely attributable to redistribution of extravascular dabigatran into the intravascular compartment. (See Re-elevation of Coagulation Parameters under Cautions.) Idarucizumab has many structural similarities to thrombin; however, it lacks thrombin-like enzymatic activity and does not bind thrombin substrates. In animal and human studies, idarucizumab did not promote or attenuate thrombin generation, suggesting that it has no intrinsic anticoagulant or procoagulant effects. The drug had no effect in stimulating platelet aggregation during in vitro studies.

Idarucizumab does not affect the activity of factor Xa inhibitors (apixaban, edoxaban, rivaroxaban), direct thrombin inhibitors (argatroban, hirudin), vitamin K antagonists (warfarin), or heparin.

Idarucizumab exhibits multiphasic disposition kinetics and limited extravascular distribution. In clinical trials, no substantial differences in plasma concentration-time profiles of idarucizumab were evident following administration of the drug alone or after pretreatment with dabigatran. Idarucizumab has an initial half-life of 47 minutes and a terminal half-life of 10.3 hours.

Idarucizumab is thought to be metabolized via biodegradation into smaller molecules (i.e., small peptides or amino acids), which are then reabsorbed and incorporated into general protein synthesis. Approximately 32% of a 5-g IV dose of idarucizumab is eliminated in urine within 6 hours followed by less than 1% of the dose during the following 18 hours; the remaining portion of drug is thought to be eliminated via protein catabolism, principally in the kidney.

Generic name: idarucizumab
Drug class: Anticoagulant Reversal Agent for Dabigatran
Therapeutic class: Antidotes and other Reversal Agents

Reference product & biosimilars

No reference, biosimilar or interchangeable associated with this drug.

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Indications

The following indications are listed for Praxbind:

  • Reversal Of Dabigatran-Induced Anticoagulation

Also known as: Reversal Of Anticoagulation Caused By Dabigatran, Reversal Of Dabigatran Anticoagulation.

Dosing

For urgent reversal of dabigatran-induced anticoagulation in patients with life-threatening or uncontrolled bleeding or in those undergoing emergency surgery/urgent procedures, the recommended dose of idarucizumab is 5 g administered in 2 divided consecutive doses (2.5 g each) by IV infusion or rapid IV injection. If clinically relevant bleeding recurs and coagulation parameters are elevated after the initial idarucizumab dose, administration of an additional 5-g dose may be considered. Similarly, patients who have elevated coagulation parameters and require a second emergency surgery/urgent procedure may be given an additional 5-g dose of idarucizumab. The safety and efficacy of repeat treatment with idarucizumab have not been well established. (See Re-elevation of Coagulation Parameters under Cautions.)

Dabigatran therapy can be reinitiated 24 hours after administration of idarucizumab; resumption of anticoagulant therapy should be considered as soon as medically appropriate. (See Thromboembolic Complications under Cautions.)

Drug interactions

There is no enhanced messaging for this drug.

Contraindications

*None.

Adverse reactions

Adverse effects reported in at least 5% of patients receiving idarucizumab in clinical studies include constipation and nausea. In phase 1 clinical trials, headache was reported in at least 5% of healthy individuals who received idarucizumab.

Precautions

No enhanced messaging available.

ICD codes

CodeTypeDescription
Reversal of dabigatran-induced anticoagulation
T45.511ICD10CMPoisoning by anticoagulants, accidental (unintentional)
T45.511AICD10CMPoisoning by anticoagulants, accidental (unintentional), initial encounter
T45.511DICD10CMPoisoning by anticoagulants, accidental (unintentional), subsequent encounter
T45.511SICD10CMPoisoning by anticoagulants, accidental (unintentional), sequela
T45.512ICD10CMPoisoning by anticoagulants, intentional self-harm
T45.512AICD10CMPoisoning by anticoagulants, intentional self-harm, initial encounter
T45.512DICD10CMPoisoning by anticoagulants, intentional self-harm, subsequent encounter
T45.512SICD10CMPoisoning by anticoagulants, intentional self-harm, sequela
T45.513ICD10CMPoisoning by anticoagulants, assault
T45.513AICD10CMPoisoning by anticoagulants, assault, initial encounter
T45.513DICD10CMPoisoning by anticoagulants, assault, subsequent encounter
T45.513SICD10CMPoisoning by anticoagulants, assault, sequela
T45.514ICD10CMPoisoning by anticoagulants, undetermined
T45.514AICD10CMPoisoning by anticoagulants, undetermined, initial encounter
T45.514DICD10CMPoisoning by anticoagulants, undetermined, subsequent encounter
T45.514SICD10CMPoisoning by anticoagulants, undetermined, sequela

ICD code information from First Databank (FDB).

Formulary status

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Last reviewed · Source: First Databank (FDB) drug data