Key pharmacological characteristics and dosing of NOACs
| . | Dabigatran . | Rivaroxaban . | Apixaban . | Edoxaban . |
|---|---|---|---|---|
| Target | Thrombin | Factor Xa | Factor Xa | Factor Xa |
| Half-life (h) | 12-14 | 9-13 | 8-15 | 9-14 |
| Metabolism via CYP450 (%) | <2 | 57 | <32 | <5 |
| Renal elimination (%) | >80* | 33†‡ | 25‡ | 50‡ |
| Drug interactions | P-gp inhibitors and inducers | Dual inhibitors and inducers of CYP3A4 and P-gp | Dual inhibitors and inducers of CYP3A4 and P-gp | P-gp inhibitors and inducers |
| AF dosing§ | 150 mg bid | 20 mg daily | 5 mg bid | 60 mg daily if CrCl >50-95 ml/min |
| Criteria for dose reduction | 75 mg bid if CrCl 15-30 ml/min or CrCl 30-50 ml/min with concomitant dronedarone or ketoconazole | 15 mg daily if CrCl 15-50 mL/min | 2.5 mg bid if at least 2 of the following: age ≥80 y, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL | 30 mg daily if CrCl 15 to 50 mL/min |
| Age-related dose adjustment | None|| | None | Age ≥80 y and either weight ≤60 kg or serum creatinine ≥1.5 mg/dL | None |
| Acute VTE dosing | 150 mg bid after LMWH | 15 mg bid for 3 wk followed by 20 mg daily | 10 mg bid for 7 d, followed by 5 mg bid | 60 mg daily after LMWH |
| Criteria for dose reduction | None|| | None | None | 30 mg daily if ≥1 of the following: CrCl 15-50 mL/min, weight ≤60 kg, or concomitant use of potent P-gp inhibitor |
| Age-related dose adjustment | None|| | None | None | None |
| Secondary VTE prevention dosing | 150 mg bid | 20 mg daily or 10 mg daily | 2.5 mg bid | 60 mg daily¶ |
| Criteria for dose reduction | None|| | None | None | 30 mg daily if ≥1 of the following: CrCl 15-50 mL/min, weight ≤60 kg, or concomitant use of potent P-gp inhibitor |
| Age-related dose adjustment | None|| | None | None | None |
| . | Dabigatran . | Rivaroxaban . | Apixaban . | Edoxaban . |
|---|---|---|---|---|
| Target | Thrombin | Factor Xa | Factor Xa | Factor Xa |
| Half-life (h) | 12-14 | 9-13 | 8-15 | 9-14 |
| Metabolism via CYP450 (%) | <2 | 57 | <32 | <5 |
| Renal elimination (%) | >80* | 33†‡ | 25‡ | 50‡ |
| Drug interactions | P-gp inhibitors and inducers | Dual inhibitors and inducers of CYP3A4 and P-gp | Dual inhibitors and inducers of CYP3A4 and P-gp | P-gp inhibitors and inducers |
| AF dosing§ | 150 mg bid | 20 mg daily | 5 mg bid | 60 mg daily if CrCl >50-95 ml/min |
| Criteria for dose reduction | 75 mg bid if CrCl 15-30 ml/min or CrCl 30-50 ml/min with concomitant dronedarone or ketoconazole | 15 mg daily if CrCl 15-50 mL/min | 2.5 mg bid if at least 2 of the following: age ≥80 y, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL | 30 mg daily if CrCl 15 to 50 mL/min |
| Age-related dose adjustment | None|| | None | Age ≥80 y and either weight ≤60 kg or serum creatinine ≥1.5 mg/dL | None |
| Acute VTE dosing | 150 mg bid after LMWH | 15 mg bid for 3 wk followed by 20 mg daily | 10 mg bid for 7 d, followed by 5 mg bid | 60 mg daily after LMWH |
| Criteria for dose reduction | None|| | None | None | 30 mg daily if ≥1 of the following: CrCl 15-50 mL/min, weight ≤60 kg, or concomitant use of potent P-gp inhibitor |
| Age-related dose adjustment | None|| | None | None | None |
| Secondary VTE prevention dosing | 150 mg bid | 20 mg daily or 10 mg daily | 2.5 mg bid | 60 mg daily¶ |
| Criteria for dose reduction | None|| | None | None | 30 mg daily if ≥1 of the following: CrCl 15-50 mL/min, weight ≤60 kg, or concomitant use of potent P-gp inhibitor |
| Age-related dose adjustment | None|| | None | None | None |
CrCl is estimated using the Cockcroft-Gault equation.
bid, twice daily; CYP450, cytochrome P450; P-gp, P-glycoprotein; LMWH, low-molecular-weight heparin.
IV dose.
Of oral absorbed drug.
Proportion of drug excreted unchanged in urine.
Most treatment guidelines recommend caution when using NOACs in patients with a CrCl between 15 and 30 mL/min and suggest that their use should be avoided in patients with a CrCl <15 mL/min.
In jurisdictions other than the United States (such as Canada and the European Union), the 110 mg twice daily dose is recommended for age ≥80 y or age >75 y with 1 risk factor for bleeding.
Not approved in the United States for secondary VTE prevention.