Table 1. Pharmacological property of new oral anticoagulants.
| Drug | Dabigatran (PRADAXA) | Rivaroxaban (XARELTO) | Edoxaban (SAVAYSA) | Apixaban (ELIQUIS) |
|---|---|---|---|---|
| Mechanism of action | Direct thrombin inhibitor | Direct factor Xa inhibitor | Direct factor Xa inhibitor | Direct factor Xa inhibitor |
| Approved indications | Stroke prevention in nonvalvular AF; VTE treatment; VTE prevention | Stroke prevention in nonvalvular AF; VTE treatment; recurrent VTE prevention; prophylaxis of VTE following hip/knee replacement | Stroke prevention in nonvalvular AF; VTE Treatment | Stroke revention in nonvalvular AF; prophylaxis of VTE following hip/knee replacement |
| Dosing in VTE | 150 mg twice daily (CrCl >30 mL/min); 75 mg twice daily (CrCl, 15–30 mL/min) | DVT; PE; and risk reduction. 15 mg twice daily with food for 21 days, then 20 mg once daily with food; hip and knee PPx: 10 mg once daily | DVT; PE: 60 mg once daily (CrCl >50 mL/min) following 5 to 10 days of parenteral anticoagulant; 30 mg once daily (CrCl 15–50 mL/min or body weight ≤60 kg) |
5 mg twice daily; 2.5 mg twice daily (age >80, body weight <60 kg, serum creatinine >1.5 mg/dL) |
| Bioavailability | 3–7% | 80–100% | 62% | 50% |
| Half-life | 12–17 h | 5–9 h | 10–14 h | 8–15 h |
| Renal elimination | >80% | 66% | 50% | 25–27% |
| Routine monitoring | No | No | No | No |
| Adverse reactions | Major bleeding, dyspepsia, nausea, upper abdominal pain, diarrhea, gastritis, hypersensitivity reaction | Major bleeding, abdominal pain, dyspepsia, toothache, fatigue, back pain, hypersensitivity, angioedema, Stevens-Johnson syndrome, cholestasis/jaundice | Major bleeding, rash, abnormal liver function tests, anemia | Major bleeding; drug hypersensitivity (<1%), nausea, transaminitis, epistaxis, hematuria, ocular hemorrhage, gingival bleeding |
| Drug interactions | Increased activity with P-gp inhibitors dronaderone, ketoconazole; decreased activity with P-gp inducer rifampin; no effect of P-gp inhibitors amiodarone, verapamil, quinidine, clarithromycin | Increased activity with CYP3A4/5, CYP2J2 inhibitors—ketoconazole, itraconzaole, ritonavir, clarithromycin; decreased activity with inducers of CYP3A4—rifampin, carbamazepine, phenytoin, St. John’s Wort | Avoid concomitant use with P-gp inducer rifampin; no dose reduction for concomitant P-gp inhibitor use | Increased activity with CYP3A4 inhibitors—ketoconazole, itraconzaole, ritonavir, clarithromycin; decreased activity with inducers of CYP3A4—rifampin, carbamazepine, phenytoin, St. John’s Wort |
| Effect on coagulation tests | ↑: TCT, ECT, aPTT; ↑ or no change: PT |
↑: anti-factor Xa; ↑ or no change: PT, aPTT; no change: TCT, ECT |
↑: anti-factor Xa; ↑ or no change: PT, aPTT | ↑: anti-factor Xa; ↑ or no change: PT, aPTT; no change: TCT, ECT |
| Reversal in emergency bleeding | Oral charcoal, hemodialysis, PCC, desmopressin, antifibrinolytic agents | PCC, desmopressin, antifibrinolytic agents | PCC, feiba, recombinant factor VIIa | PCC, desmopressin, antifibrinolytic agents |
Data obtained from Pradaxa (dabigatran etexilate) US Prescribing Information, Xarelto (rivaroxaban) US Prescribing Information, Eliquis (Apixaban) US Prescribing Information, Savaysa (Edoxaban) US Prescribing Information. AF, atrial fibrillation; VTE, venous thromboembolism; PPx, prophylaxis; CrCl, creatinine clearance; CYP3A4, cytochrome P450 3A4; CYP2J2, cytochrome P450 2J2; PT, prothrombin time; aPTT, activated partial thromboplastin time; TCT, thrombin clotting time; ECT, ecarin clotting time; PCC, prothrombin complex concentrate.