Reversal agent
Idarucizumab (Praxbind)
Also called Praxbind
Watch the explainer
Heparin vs Warfarin: aPTT vs INR, HIT, Bridging, Antidotes and DOAC Reversal
Indications
- Dabigatran with life-threatening or uncontrolled bleeding (label)
- Dabigatran before emergency surgery or an urgent procedure (label)
- Dabigatran-treated stroke patients otherwise eligible for IV thrombolysis: reverse, then lyse (off-label; case series)
Dosing
| Where | Dose |
|---|---|
| Reversal and antidotes | Idarucizumab (Praxbind): 5 g IV (two 2.5 g vials) for dabigatran |
On the quick cards
Mechanism of action
Idarucizumab is a humanized monoclonal antibody fragment (Fab) that binds dabigatran and its active acylglucuronide metabolites, both free and bound to thrombin. It holds dabigatran about 350 times more tightly than dabigatran holds thrombin (Schiele 2013), binding 1:1 and essentially irreversibly, so thrombin is released and the anticoagulant effect disappears within minutes. Its binding pocket mimics thrombin's active site, but it binds no thrombin substrates and has no procoagulant or anticoagulant effect of its own.
Pharmacology
- Hematologic: dilute thrombin time, ecarin clotting time, aPTT and ACT normalize right after the 5 g dose; median maximum reversal 100% (RE-VERSE AD)
- Hematologic: bleeding stopped at a median of 2.5 h, and periprocedural hemostasis was normal in 93% (RE-VERSE AD 2017)
- Hematologic: no procoagulant effect of its own (label) and no effect on warfarin, heparins or factor Xa inhibitors
- Renal: the kidneys clear both the antibody and dabigatran, so kidney failure raises exposure to both (label)
Pharmacokinetics
| Onset | Immediate: unbound dabigatran below quantification after the dose (label) |
|---|---|
| Duration | Usually lasting; clotting times rose again at 12–24 h in some as dabigatran returned from tissues (label) |
| Half-life | Initial 47 min; terminal 10.3 h (label) |
| Distribution | Vd 8.9 L (label) |
| Metabolism | Protein catabolism, mainly in the kidney (label) |
| Clearance | 47 mL/min (label) |
| Elimination | Glomerular filtration, then tubular reabsorption and breakdown; 32% in urine within 6 h (label) |
| Organ failure | Exposure up 44% in mild and 84% in moderate kidney impairment; no dose change (label) |
| Dialysis | Removes dabigatran (about 35% protein bound), a fallback when idarucizumab is unavailable |
Chemistry
- Humanized Fab fragment of an IgG1 antibody made in CHO cells: a 219-amino acid light chain and a 225-amino acid heavy-chain fragment, about 47.8 kDa (label)
- No Fc region, so no Fc receptor or complement effects
- Ready-to-use 2.5 g/50 mL (50 mg/mL) vials, two per dose, with acetate buffer, polysorbate 20 and 2 g sorbitol each; pH about 5.5
- Refrigerate in the carton; unopened vials keep 48 h at room temperature, or 6 h exposed to light; do not freeze or shake; flush an existing line with saline first (label)
Adverse effects and cautions
In the one-pagers
- Pharmacology by Class and SuffixAntidotes and reversal: Dabigatran (-gatran): Idarucizumab
- Blood Products and TransfusionAnticoagulant reversal: Dabigatran: Idarucizumab 5 g IV: Antibody fragment that binds dabigatran
- High-Alert Meds and InsulinAnticoagulants: Dabigatran: None routine: Idarucizumab 5 g IV
Other reversal agent drugs
Sources
- FDA label: Praxbind (2023)
- Schiele 2013 (Blood)
- Pollack 2017 (RE-VERSE AD, NEJM)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.