Idarucizumab

Although there is insufficient clinical experience with idarucizumab to fully evaluate the risk of hypersensitivity reactions, some reported adverse events possibly indicative of hypersensitivity reactions could not exclude a potential relationship. The risk of using idarucizumab in patients with known hypersensitivity (eg, anaphylactoid reaction) to idarucizumab or any of the components of the formulation should be evaluated cautiously against the potential benefit of emergency dabigatran reversal. Discontinue use if serious allergic reaction occurs (eg, anaphylaxis) and institute appropriate management.

Since patients being treated with dabigatran, have underlying disease states predisposing them to thromboembolic events and reversing the effects of dabigatran will expose the patient to an elevated thrombotic risk; resume anticoagulant therapy as soon as it is appropriate. Dabigatran can be re-initiated 24 hours after idarucizumab administration if appropriate. In the phase 3 clinical trial, not all thromboembolic events that occurred reflected the underlying disease state being treated with dabigatran; adverse thromboembolic events included DVT, PE, atrial thrombus, NSTEMI, and ischemic stroke (Pollack 2015). Disease-related concerns:

Formulation contains 4 grams of sorbitol as an excipient. Since IV administration of sorbitol in patients with hereditary fructose intolerance has been reported to result in serious reactions (eg, acute hepatic failure, hypoglycemia, hypophosphatemia, metabolic acidosis, uric acid elevations) including fatalities, consider the combined daily metabolic load of sorbitol/fructose from all sources including idarucizumab and other drugs containing sorbitol; minimum amount of sorbitol known to cause serious adverse reactions is unknown. Other warnings/precautions:

Although the duration of effect typically lasts at least 24 hours, in the phase 3 clinical trial, coagulation parameters (eg, aPTT, TT, ecarin clotting time [not routinely available]) re-elevated in a limited number of patients between 12 and 24 hours after administration; some patients experienced re-elevation as early as 1 to 4 hours after administration which may have been due to high initial baseline dabigatran concentrations. If clinically relevant bleeding in conjunction with elevated coagulation parameters reoccurs following an idarucizumab 5 g dose, administration of a second dose should be considered (Pollack 2015; Pollack 2017).

Potential for incomplete reversal of dabigatran exists with idarucizumab. Case reports have described patients with very high initial serum dabigatran concentrations who experienced unsuccessful reversal of the anticoagulant effects of dabigatran after idarucizumab and required repeat doses; early detection of excessive dabigatran concentrations measured using the chromogenic ecarin clotting time assay or reflected as elevated coagulation parameters (ie, INR or thrombin time) is essential (Steele 2017).