• the use of idarucizumab as an antidote to reverse the anticoagulant effects of dabigatran was approved by the FDA in October 2015   [Cassels, 2015]
  • it has a 300-fold greater affinity for thrombin than does dabigatran
  • indicated for adult patients treated with dabigatran (PRADAXA) when rapid reversal of anticoagulant effects is needed:
    • urgent surgery or procedures (including intravenous thrombolysis)
    • life-threatening or uncontrolled bleeding (including ICH)
  • virtually no contraindications (except allergy), relevant drug interactions, or adverse events (AEs)

Mechanism of action

  • idarucizumab is a fragment of a humanized monoclonal antibody that acts as a specific reversal agent for dabigatran
  • it forms a tight complex with dabigatran and its acyl glucuronide metabolites, thereby immediately neutralizing the anticoagulant effect of dabigatran
    • dabigatran has a 300-fold higher affinity for idarucizumab than for thrombin
  • no interference with other anticoagulants and no secondary hypercoagulable state is induced
  • administered as an IV bolus with rapid onset of action
  • allows for the rapid resumption of anticoagulant therapy (within 24 hours post-administration)
  • several pathways contribute to antibody metabolism; all  involve the biodegradation of antibodies into smaller molecules, which are subsequently reabsorbed and incorporated into general protein synthesis
Idarucizumab (PRAXBIND) - mechanism of action

Clinial trials

  • RE-VERSE AD trial with idarucizumab at a dose of 5g IV
    • effective within minutes
    • analysis of 90 patients showed a reliable reduction of anticoagulant activity, achieving normal coagulation in 90% of patients at 4 and 12 hours  → see here
  • growing clinical experience exists with idarucizumab administration before thrombolysis and in the acute treatment of intracranial hemorrhage (ICH) see here
Results of REVERESE-AD trial
REVERSE-AD trial results

Contraindications and precautions

  • allergy to idarucizumab or its ingredients
  • patients with hereditary fructose intolerance may be at risk of adverse reactions (such as hypoglycemia, hypophosphatemia, metabolic acidosis, elevated uric acid, and acute liver failure)
  • no adequate and well-controlled studies in pregnant women
  • it is not known whether idarucizumab can cause fetal harm when administered to a pregnant woman ⇒ should be given only if absolutely necessary
  • no data available regarding its use during labor and delivery
  • it is unknown whether idarucizumab passes into human milk
  • no data are available on the effects of idarucizumab on nursing infants or on milk production
  • the benefits of breastfeeding should be weighed against the mother’s clinical need for the drug (the benefits must outweigh the risks)

Idarucizumab administration

  • aseptic handling is required during the preparation
  • visually inspect for particulates and discoloration before infusion
  • once the solution is withdrawn from the vial, administration should begin immediately; vials may be stored at room temperature (25°C /77°F) but must be used within 6 hours
  • do not mix with other medications


    • vial  = 2.5g/50 mL
    • administer a 5g dose intravenously as two consecutive 2.5 g infusions or bolus injections
    • an existing intravenous line may be used; flush with sterile 0.9% NS solution before infusion
    • no other infusion should be administered simultaneously via the same IV access
    • renal impairment does not affect the reversal effect of idarucizumab ⇒ no dose adjustment is required
Idarucizumab (PRAXBIND) administration

Resuming antithrombotic therapy

  • patients treated with dabigatran have underlying conditions predisposing them to thromboembolic events
  • consider resumption of anticoagulant therapy ASAP to reduce this risk
  • idarucizumab does not interfere with other anticoagulant or antithrombotic therapies
  • dabigatran treatment can be resumed 24 hours after idarucizumab administration

Praxbind and intravenous thrombolysis

  • intravenous thrombolysis (IVT)  in acute stroke patients on dabigatran is possible with dabigatran therapy if aPTT + TT, ECT, or HEMOCLOT values do not exceed upper limits of normal  (AHA/ASA 2013 III/C)
    • a normal aPTT alone is not sufficient as it does not completely rule out an elevated TT  [Kermer, 2017] [Hankey, 2014]
    • IVT may be considered with normal TT or TT <60 s AND normal APTT   (ESO guidelines 2021)

      • expert opinion only; insufficient evidence to make an evidence-based recommendation
    • Hemoclot – a dabigatran level < 50 ng/ml > 6h after the last dose of the drug indicates the absence of anticoagulant activity
  • administration of thrombolysis after prior neutralization with PRAXBIND is possible (IVT is an emergency procedure); registry data suggest that administration of the antidote PRAXBIND in patients with acute stroke followed by thrombolysis is effective, safe, and easy to perform [Kermer, 2017]
    • expert consensus suggests a combination of idarucizumab and IVT for patients with acute ischemic stroke of <4.5 hours duration (ESO guidelines 2021)  [Diener, 2017]

Adverse events

  • common side effects
    • hypokalemia (7%)
    • delirium (7%)
    • constipation (7%)
    • fever (6%)
    • pneumonia (6%)
    • headache (5%)
  • serious side effects:
    • thrombosis/thromboembolism – patients are at increased thrombotic risk due to the underlying condition necessitating dabigatran prescription
    • recurrent bleeding (some patients may require an additional dose of idarucizumab)
    • hypersensitivity reactions (severe allergic reaction – fever, respiratory distress due to airway spasms, hyperventilation, rash, and pruritus)
  • patients with hereditary fructose intolerance may be at risk for adverse effects such as hypoglycemia, hypophosphatemia, metabolic acidosis, hyperuricemia, and acute liver failure

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Idarucizumab (PRAXBIND)
link: https://www.stroke-manual.com/praxbind-idarucizumab/