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Reversal of dabigatran: Reversal of the anticoagulant effects of dabigatran for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding
There are no contraindications listed in the US labeling.
Canadian labeling: Hypersensitivity to idarucizumab or any component of the formulation
Reversal of dabigatran: IV: 5 g (administered as 2 separate 2.5 g doses no more than 15 minutes apart) (Pollack 2015). If coagulation parameters (eg, aPTT) re-elevate and clinically relevant bleeding occurs or if a second emergency surgery/urgent procedure is required and patient has elevated coagulation parameters, may consider administration of an additional 5 g (limited data to support).
Refer to adult dosing.
No dosage adjustment necessary; renal impairment does not impact the reversal effect of idarucizumab.
There are no dosage adjustments provided in the manufacturers labeling (has not been studied).
May withdraw contents of each vial using a 60 mL syringe to be administered as an IV bolus or may hang each vial and administer as an infusion.
IV: 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. 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]). Do not administer any other infusion in the same IV line. Begin administration within 1 hour of removing the solution from the vial.
Store intact vials at 2 ‚ ºC to 8 ‚ ºC (36 ‚ ºF to 46 ‚ ºF). Do not freeze. Do not shake. May store intact vial in the original packaging (to protect from light) prior to use at room temperature 25 ‚ °C (77 ‚ °F) for up to 48 hours, or up to 6 hours if exposed to light.
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)
There are no known significant interactions.
Monitor for re-elevation of coagulation parameters (eg, aPTT); signs/symptoms of clinically relevant bleeding and thromboembolic events.
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.
Frequency not always defined.
Central nervous system: Delirium (7%), headache (5%)
Endocrine & metabolic: Hypokalemia (7%)
Gastrointestinal: Constipation (7%)
Hypersensitivity: Hypersensitivity (including bronchospasm, hyperventilation, rash, and pruritus)
Respiratory: Pneumonia (6%)
Miscellaneous: Fever (6%)
<1% (Limited to important or life-threatening) (Pollack 2015): Acute ischemic stroke, cardiac arrest, circulatory shock, deep vein thrombosis, intracardiac thrombus (left atrium), multiorgan failure, non-ST-segment elevation myocardial infarction, pulmonary edema, pulmonary embolism, respiratory failure, right heart failure
Total clearance was reduced in mild (CrCl 60 to 90m mL/minute) and moderate (CrCl 30 to <60 mL/minute) impairment, resulting in an increase in the AUC by ~44% and ~84%, respectively. However, renal impairment did not impact the reversal effect of idarucizumab.
Concerns related to adverse effects:
- 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 (Pollack 2015). If clinically relevant bleeding in conjunction with elevated coagulation parameters reoccurs following an idarucizumab 5 g dose, administration of a second dose may be considered.
- 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 (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.
Animal reproduction studies have not been conducted.
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).
Vdss: 8.9 L
Biodegradation of small peptides and amino acids
Urine (~32% within the first 6 hours and <1% in the following 18 hours)
Uncontrolled bleeding: Effects observed within minutes and hemostasis is restored at a median of 11.4 hours (Pollack 2015)
Usually at least 24 hours
47 minutes (initial); 10.3 hours (terminal)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache or constipation. Have patient report immediately to prescriber signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; fast heartbeat; or coughing up blood), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), bleeding, confusion, shortness of breath, cough, or fast breathing (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience,and judgment in diagnosing, treating, and advising patients.