An Update on the Reversal of Non-Vitamin K Antagonist Oral Anticoagulants

Table 1

Available NOAC-specific Reversal agents for Non-vitamin K Antagonist Oral Anticoagulants.

	Idarucizumab	Andexanet alfa	Ciraparantag [46]
Structure	Monoclonal antibody fragment	Modified factor Xa decoy protein	Synthetic water-soluble molecule
FDA status	Approved	Approved	Under FDA review
NOACs reversed	Dabigatran	Apixaban	Apixaban
		Rivaroxaban	Rivaroxaban
			Edoxaban
			Dabigatran
Mechanism of action	Binds free and thrombin-bound dabigatran	Binds to the active site of factor Xa inhibitors	Direct binding to anticoagulants
Onset of action	10–30 minutes	2–5 minutes	10 minutes
Half-life	45 minutes	1 hour	45 minutes
Dosage form	2.5 g/50 mL solution in a single-dose vial	100 mg and 200 mg vials to be reconstituted with 10 mL or 20 mL sterile water respectively	—
Dose	5 g IV given as two-50 mL bolus infusions with 2.5 g each within 15 minutes apart	Low dose: 400 mg IV bolus at a target rate of 30 mg/min then a 4 mg/min continuous infusion for 120 minutes (480 mg)	100 to 300 mg IV one time bolus
		High Dose1: 800 mg IV bolus at a target rate of 30 mg/min then an 8 mg/min continuous infusion for 120 minutes (960 mg)
Dose adjustment	None reported	None reported	None reported
Contraindications	None reported	None reported	None reported
Adverse reactions	REVERSE-AD: 30-day thrombotic events 4.8%	ANEXXA-4: 30-day thrombotic events 10%	Perioral and facial flushing, dysgeusia [46]
			No pro-coagulant activities reported on current clinical data
	Others:	Others:
	Constipation 7%	Urinary tract infection >5%
	Headache >5%	Pneumonia >5%
	Nausea 5%	Infusion-related reactions >3%
	Hypersensitivity reactions
Cost	$3,482 per reversal^3	Low dose: $29,040	—
		High dose: $58,080
		Calculated from $3,300 per 100 mg vial^2

¹Indications for high-dose and exanet alfa: Rivaroxaban: Last dose >10 mg or unknown AND received within <8 hours or unknown. Apixaban: Last dose >5 mg or unknown AND received within <8 hours or unknown. ²Approximate wholesale acquisition cost or manufacturer’s published price. ³Buchheit J, Reddy P, Connors JM. Idarucizumab (Praxbind) Formulary Review. Crit Pathw Cardiol. 2016; 15 (3):77–81. Based on current available data.