Basic Neuroscience · Neuropharmacology
Direct Oral Anticoagulants (DOACs)
Direct oral anticoagulants (DOACs) for neurology — target, dosing (atrial fibrillation and VTE), renal adjustment, reversal, and precautions. A one-page printable version is available via the Download PDF button above. Verify all doses and indications before prescribing.
| Agent | Target & clearance | Atrial fib dose | VTE treatment dose | Renal adjustment & cautions | Reversal |
|---|---|---|---|---|---|
| Apixaban (Eliquis) | Factor Xa inhibitor. ~27% renal (least). | 5 mg BID; 2.5 mg BID if ≥2 of: age ≥80, wt ≤60 kg, Cr ≥1.5. | 10 mg BID ×7 d, then 5 mg BID. | Best in low CrCl / dialysis (per label). Least bleeding in trials. | PCC |
| Rivaroxaban (Xarelto) | Factor Xa inhibitor. ~35% renal; CYP3A4. | 20 mg daily with evening meal. | 15 mg BID ×21 d, then 20 mg daily. | 15 mg if CrCl 15–50; avoid CrCl <15. Take with food. | PCC |
| Edoxaban (Savaysa) | Factor Xa inhibitor. ~50% renal. | 60 mg daily (30 mg if wt ≤60 kg). | 60 mg daily after ≥5 d parenteral. | 30 mg if CrCl 15–50. Avoid in AF if CrCl >95 (reduced efficacy). | PCC |
| Dabigatran (Pradaxa) | Direct thrombin (IIa) inhibitor. ~80% renal. | 150 mg BID. | 150 mg BID after ≥5 d parenteral heparin. | CrCl 15–30: 75 mg BID; CrCl <15: avoid. Dyspepsia. Dialyzable. | Idarucizumab |
When to Avoid & Key Interactions
| Situation / combination | Why it matters | What to do |
|---|---|---|
| DOAC + mechanical heart valve or mod–severe mitral stenosis | DOACs failed (↑ thrombosis & bleeding, RE-ALIGN). | Avoid — use warfarin. |
| DOAC + antiphospholipid syndrome (triple-positive) | ↑ recurrent thrombosis vs warfarin. | Avoid — use warfarin. |
| DOAC + severe renal impairment / dialysis | Accumulation → bleeding (esp. dabigatran). | Apixaban only (per label); avoid others. |
| DOAC + antiplatelet / NSAID | Additive bleeding (esp. GI). | Minimize duration; GI protection; reassess need. |
| DOAC + SSRIs | Moderate ↑ bleeding risk. | Caution; counsel on bleeding; consider GI protection. |
| DOAC + strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, phenobarbital, St John's wort) | ↓ DOAC levels → ↓ efficacy (thrombosis). | Avoid; use a non-enzyme-inducing AED. |
| DOAC + strong CYP3A4 inhibitors (azoles, ritonavir, clarithromycin) | ↑ DOAC levels → ↑ bleeding. | Avoid or dose-reduce per label. |
Reversal Agents
| Reversal agent | Reverses (which drugs) | Dose & notes |
|---|---|---|
| Idarucizumab (Praxbind) | Dabigatran — specific antidote. | 5 g IV (two 2.5 g boluses). |
| 4-factor PCC — Kcentra (standard) | Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban); also warfarin. | 25–50 units/kg. |
| FEIBA (activated PCC) | Factor Xa inhibitors — alternative to Kcentra. | 25–50 units/kg; showed equivalent hemostasis to Kcentra in studies. |
Andexanet alfa (Andexxa) — specific factor Xa reversal, now discontinued.
Neuro Pearls
- Restart after cardioembolic (AF) stroke — start early: OPTIMAS (≤4 days) and ELAN (≤48 h for minor–moderate; ~day 6–7 for large infarcts).
- After ICH: hold for a few weeks, then reassess thrombotic vs bleeding risk; consider left atrial appendage occlusion (LAAO).
- Prefer apixaban in renal impairment, high GI-bleed risk, or the elderly; avoid edoxaban if CrCl >95 in AF.