Reversal of dabigatran:
Note: Generally used for life-threatening bleeding, bleeding into a critical organ, or prior to an emergency procedure if maximal supportive measures (eg, activated charcoal [if ingestion is within ~2 to 4 hours], antifibrinolytic agent, hemodialysis) are not adequately effective (ACC [Tomaselli 2020]; Baugh 2019; Cuker 2019).
IV: 5 g (administered as 2 separate 2.5 g doses no more than 15 minutes apart). Note: Repeat dosing is not usually required. However, another dose may be considered (despite limited data) if bleeding continues and there is laboratory evidence of persistent dabigatran effect or before an emergent invasive procedure if there is concern for a persistent anticoagulant effect (ACC [Tomaselli 2020).
No dosage adjustment necessary; renal impairment does not impact the reversal effect of idarucizumab.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Praxbind: 2.5 g/50 mL (50 mL)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Praxbind: 2.5 g/50 mL (50 mL)
IV: For IV use only. Do not shake. Prior to administration, flush preexisting IV line with sodium chloride 0.9%. Administer dose undiluted as an IV bolus either via syringe or as an infusion by hanging the vials. Do not mix with other drugs or administer any other infusion in the same IV line. Administer promptly once solution has been removed from vial. Infusion of each vial should take no longer than 5 to 10 minutes with the second vial of 2.5 g administered no later than 15 minutes after the end of the first 2.5 g vial (Pollack 2015 [protocol]).
Reversal of dabigatran: Reversal of the anticoagulant effects of dabigatran for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding.
IdaruCIZUmab may be confused with IDArubicin, inFLIXimab, ipilimumab
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Central nervous system: Headache (5%)
Gastrointestinal: Constipation (7%), nausea (5%)
Frequency not defined:
Hypersensitivity: Hypersensitivity reaction (including bronchospasm, fever, hyperventilation, pruritus, skin rash)
<1%, postmarketing, and/or case reports (Pollack 2015): Acute ischemic stroke, circulatory shock, deep vein thrombosis, intracardiac thrombus (left atrium), multiorgan failure, myocardial infarction (NSTEMI), pulmonary edema, pulmonary embolism, right heart failure, thromboembolic complications (Pollack 2017)
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to idarucizumab or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity reactions: 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.
• Thromboembolic risk: 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 (Giannandrea 2018; Pollack 2015).
Disease-related concerns:
• Hereditary fructose intolerance: 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:
• Coagulation parameter re-elevation: 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).
• Incomplete reversal: 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).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Animal reproduction studies have not been conducted.
It is not known if idarucizumab is present in breast milk. The manufacturer recommends that caution be exercised when administering idarucizumab to breastfeeding women.
Monitor for re-elevation of coagulation parameters (eg, aPTT); signs/symptoms of clinically relevant bleeding and thromboembolic events. Clinicians should note that a paradoxical increase in dabigatran concentrations may occur following idarucizumab administration, even with successful reversal, due to the measurement of both free and idarucizumab-bound dabigatran (Hosoki 2018).
In patients overdosed with dabigatran, consider the following monitoring schedule (Alikhan 2014): Baseline aPTT (at presentation), repeat at 2 hours postexposure (if exposure time is known) or post-presentation (if exposure time is unknown) and every 12 hours thereafter until aPTT returns to normal.
Idarucizumab, a specific reversal agent for dabigatran, is a humanized monoclonal antibody fragment (Fab) that binds specifically to dabigatran and its acylglucuronide metabolites with an affinity for dabigatran that is ~350 times greater than that of thrombin, and neutralizes the anticoagulant effect within minutes (Das 2015; Schiele 2013).
Onset: Uncontrolled bleeding: Effects observed within minutes and hemostasis is restored at a median of 11.4 hours (Pollack 2015)
Duration: Usually at least 24 hours
Distribution: Vdss: 8.9 L
Metabolism: Biodegradation to small peptides and amino acids
Half-life elimination: 47 minutes (initial); 10.3 hours (terminal)
Excretion: Urine (~32% within the first 6 hours and <1% in the following 18 hours)
Altered kidney function: Total clearance was reduced. However, renal impairment did not impact the reversal effect of idarucizumab.
Solution (Praxbind Intravenous)
2.5 gm/50 mL (per mL): $53.41
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