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Introduction

  1. Pharmacology
    1. Idarucizumab is a humanized monoclonal antibody fragment specific to the oral direct thrombin inhibitor dabigatran. It binds to the thrombin binding site on dabigatran with 350 times greater affinity than thrombin, and it also binds dabigatran's acylglucuronide metabolites.
    2. Pharmacokinetics: Complete reversal of dabigatran effect occurs within 1 minute of bolus infusion and lasts 12-24 hours. Elimination occurs through urinary excretion (32%) and protein catabolism, mainly in the kidney. Patients with renal insufficiency have decreased clearance of idarucizumab, with an increased area under the curve (AUC) of as much as 146% in patients with a creatinine clearance less than 30 mL/min.
  2. Indications
    1. Reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran.
  3. Contraindications
    1. Anaphylaxis to idarucizumab or its components.
    2. Caution in patients with hereditary fructose intolerance due to presence of sorbitol excipient.
  4. Adverse effects
    1. In patients on dabigatran for thromboembolic disease, reversal of dabigatran therapy will expose patients to the thrombotic risk of their underlying disease.
    2. Rebound anticoagulation may occur 12-24 hours after receiving idarucizumab.
    3. Hypersensitivity reactions including anaphylactoid and anaphylactic reactions.
    4. In patients with hereditary fructose intolerance, parenteral administration of sorbitol (excipient) can result in serious, sometimes fatal, adverse reactions. Reported reactions include hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, and acute hepatic failure.
    5. Antibodies to idarucizumab have been reported in 2-4% of cases; clinical implications unknown.
    6. Use in pregnancy: There is no clinical trial data on the use of idarucizumab in pregnancy, labor, delivery, or lactation.
  5. Drug or laboratory interactions
    1. No known drug interactions other than reversal of the effects of dabigatran.
  6. Dosage and method of administration
    1. Idarucizumab is administered in a total dose of 5 g (two 2.5-g vials). Each vial is given over 5-10 minutes with the second vial started no more than 15 minutes after the first vial administration is complete.