Characteristics of available DOACs for VTE treatment
| . | Dabigatran . | Rivaroxaban . | Apixaban . | Edoxaban . |
|---|---|---|---|---|
| Target | Flla | FXa | FXa | FXa |
| Therapeutic dose | 150 mg twice a day; 110 mg twice a day for patients aged >80 y; 110 mg twice a day following at least 5 d of parenteral anticoagulants for patients with a high risk of bleeding | 15 mg twice a day for 3 wk followed by 20 mg once a day | 10 mg twice a day for 7 d, followed by 5 mg twice a day | 60 mg once a day following ≥5 d of parenteral anticoagulants |
| Prodrug | Yes | No | No | No |
| Bioavailability | 3-7% | 10 mg dose: 100%; 20 mg dose: 100% when taken with food; 66% under fasting conditions; interindividual variability: 30-40% | ∼50%; interindividual variability: 30% | ∼62% |
| Activity onset | 1-3 h | 2-4 h | 3-4 h | 1-2 h |
| Half-life | 12-18 h | 5-13 h | 12 h | 10-14 h |
| Excretion (% of administered dose) | 80% renal (unchanged), 20% liver | 66% renal (half active drug unchanged and half inactive metabolites), 33% feces (inactive metabolites) | 25% renal, 75% feces | 50% renal (unchanged, 50% biliary or intestinal) |
| Considerations for renal insufficiency | Mild or moderate: dose adjustment recommended; severe: contraindicated if GFR <30 mL/min | Moderate (GFR 30-49 mL/min): dose adjustment recommended; severe: not recommended if GFR <30 mL/min | Mild or moderate, or if GFR >25-30 mL/min: no dose adjustment required; severe: not recommended if GFR <15 mL/min; no data available in patients with end-stage renal disease | Moderate (GFR, 30-50 mL/min): dose adjustment recommended; severe: not recommended if GFR <15 mL/min; no data available in patients with end-stage renal disease or on dialysis |
| Considerations for hepatic insufficiency | Liver enzymes twice normal limit or if acute liver diseases: not recommended | Moderate hepatic impairment: caution; hepatic disease with coagulopathy and clinically relevant bleeding risk: contraindicated | Mild or moderate hepatic impairment: caution, but no dose adjustment required; severe hepatic impairment: not recommended; hepatic disease with coagulopathy and clinical relevant bleeding risk: contraindicated | Mild hepatic impairment: no dose reduction; moderate or severe hepatic impairment: not recommended |
| Interaction | P-glycoprotein inducers or inhibitors | P-glycoprotein inducers or inhibitors; CYP3A4 and CYP2J2 | P-glycoprotein inducers or inhibitors; CYP3A4 | P-glycoprotein inducers or inhibitors; CYP3A4 |
| Antidote | Idarucizumab | None | None | None |
| . | Dabigatran . | Rivaroxaban . | Apixaban . | Edoxaban . |
|---|---|---|---|---|
| Target | Flla | FXa | FXa | FXa |
| Therapeutic dose | 150 mg twice a day; 110 mg twice a day for patients aged >80 y; 110 mg twice a day following at least 5 d of parenteral anticoagulants for patients with a high risk of bleeding | 15 mg twice a day for 3 wk followed by 20 mg once a day | 10 mg twice a day for 7 d, followed by 5 mg twice a day | 60 mg once a day following ≥5 d of parenteral anticoagulants |
| Prodrug | Yes | No | No | No |
| Bioavailability | 3-7% | 10 mg dose: 100%; 20 mg dose: 100% when taken with food; 66% under fasting conditions; interindividual variability: 30-40% | ∼50%; interindividual variability: 30% | ∼62% |
| Activity onset | 1-3 h | 2-4 h | 3-4 h | 1-2 h |
| Half-life | 12-18 h | 5-13 h | 12 h | 10-14 h |
| Excretion (% of administered dose) | 80% renal (unchanged), 20% liver | 66% renal (half active drug unchanged and half inactive metabolites), 33% feces (inactive metabolites) | 25% renal, 75% feces | 50% renal (unchanged, 50% biliary or intestinal) |
| Considerations for renal insufficiency | Mild or moderate: dose adjustment recommended; severe: contraindicated if GFR <30 mL/min | Moderate (GFR 30-49 mL/min): dose adjustment recommended; severe: not recommended if GFR <30 mL/min | Mild or moderate, or if GFR >25-30 mL/min: no dose adjustment required; severe: not recommended if GFR <15 mL/min; no data available in patients with end-stage renal disease | Moderate (GFR, 30-50 mL/min): dose adjustment recommended; severe: not recommended if GFR <15 mL/min; no data available in patients with end-stage renal disease or on dialysis |
| Considerations for hepatic insufficiency | Liver enzymes twice normal limit or if acute liver diseases: not recommended | Moderate hepatic impairment: caution; hepatic disease with coagulopathy and clinically relevant bleeding risk: contraindicated | Mild or moderate hepatic impairment: caution, but no dose adjustment required; severe hepatic impairment: not recommended; hepatic disease with coagulopathy and clinical relevant bleeding risk: contraindicated | Mild hepatic impairment: no dose reduction; moderate or severe hepatic impairment: not recommended |
| Interaction | P-glycoprotein inducers or inhibitors | P-glycoprotein inducers or inhibitors; CYP3A4 and CYP2J2 | P-glycoprotein inducers or inhibitors; CYP3A4 | P-glycoprotein inducers or inhibitors; CYP3A4 |
| Antidote | Idarucizumab | None | None | None |
Reprinted with permission from Elsevier/The Lancet Oncology.13
Flla. thrombin; FXa, factor Xa; GFR, glomerular filtration rate.