Table 1. Pharmacological properties of new oral anticoagulants.
| Drug | Dabigatran (pradaxa™) | Rivaroxaban (xarelto™) | Apixaban (eliquis™) |
|---|---|---|---|
| Mechanism of action | Direct thrombin 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; prophylaxis of VTE following hip/knee replacement |
| Dosing in AF | 150 mg twice daily (CrCl >30 mL/min) | 20 mg once daily (CrCl >50 mL/min) | 5 mg twice daily |
| 75 mg twice daily (CrCl 15-30 mL/min) | 15 mg once daily (CrCl 15-50 mL/min) | 2.5 mg twice daily (age >80, body weight <60 kg, serum creat >1.5 mg/dL) | |
| Bioavailability (%) | 3-7 | 80-100 | 50 |
| Half-life (h) | 12-17 | 5-9 | 8-15 |
| Renal elimination (%) | >80 | 66 | 25-27 |
| Routine monitoring | 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; 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 |
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 No change: TCT, ECT |
| Reversal in emergency bleeding | Oral charcoal Hemodialysis PCC Desmopressin Antifibrinolytic agents |
PCC Desmopressin Antifibrinolytic agents |
PCC Desmopressin Antifibrinolytic agents |
AF, atrial fibrillation; VTE, venous thromboembolism; 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. Data obtained from Pradaxa (dabigatran etexilate) US Prescribing Information, Xarelto (rivaroxaban) US Prescribing Information, Eliquis (Apixaban) US Prescribing Information.