Idarucizumab
Praxbind
Monoclonal antibody fragment that binds dabigatran with approximately 300 times higher affinity than dabigatran binds to thrombin — in practice it never lets go. The effect is immediate and complete: unbound dabigatran in plasma falls by over 99 per cent directly after the infusion. The specificity is also the limitation — it does nothing at all against apixaban, rivaroxaban, edoxaban, warfarin, or heparin.
Idarucizumab reverses only dabigatran. If given for bleeding on a factor Xa inhibitor, time is lost without any effect. Confirm which agent the patient is actually taking before the dose is given, and remember that reversal exposes the patient's underlying thrombotic risk.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Life-threatening or uncontrolled bleeding on dabigatran | 5 g iv, that is two vials of 2,5 g/50 ml, given as two consecutive infusions over 5–10 minutes each or as bolus | effect is immediate, no weight adjustment |
| Emergency surgery or urgent procedure | same dose: 5 g iv as two infusions of 2,5 g | the procedure can begin immediately after the infusion is complete |
| Recurrent bleeding within one day | a further 5 g iv may be considered in renewed clinically relevant bleeding with prolonged coagulation times | redistribution from peripheral tissue is seen 1–24 hours after the dose |
| Restarting dabigatran | may be restarted 24 hours after idarucizumab | requires stable patient and achieved haemostasis |
| Other antithrombotic treatment | low molecular weight heparin and other antithrombotics may be started at any time after idarucizumab | without anticoagulation, the underlying disease's thrombotic risk remains |
No dose adjustment. Exposure increases with falling renal function — approximately 38 per cent at eGFR 50–80, 90 per cent at 30–50, and 146 per cent below 30 ml/min — but the reversal effect is not affected.
No dose adjustment in hepatic impairment.
Safety and efficacy below 18 years have not been established. Only isolated treated patients are described, with the same pharmacokinetics as in adults.
Do not use idarucizumab as a general bleeding antidote. In bleeding on apixaban, rivaroxaban, or edoxaban it is ineffective and prothrombin complex concentrate is indicated instead. Also withhold reversal in merely elevated coagulation times without bleeding or urgent procedure — the benefit exists only when the bleeding or surgery is real, while the thrombotic risk after reversal always is.
Pharmacokinetics
- ONSET
- immediate
- t½ (initial)
- 47 minutes
- t½ (terminal)
- 10,3 hours
- Vd (steady state)
- 8,9 l
- CLEARANCE
- 47 ml/min
- EXCRETION
- Renal, 32 % within 6 hours; remainder via protein catabolism
- AFFINITY
- approximately 300 × dabigatran's affinity for thrombin
- MOLECULE
- Humanised monoclonal Fab fragment