Pharmacologic properties of DOAC agents
| Variable . | Dabigatran etexilate . | Rivaroxaban . | Apixaban∗ . | Edoxaban∗ . |
|---|---|---|---|---|
| Prodrug | Yes | No | No | No |
| Mechanism of action | Direct IIa inhibitor; inhibits clot-bound and free thrombin | Direct Xa inhibitor; inhibits clot-bound and free Xa | Direct Xa inhibitor; inhibits clot-bound and free Xa | Direct Xa inhibitor; inhibits clot-bound and free Xa |
| Time to onset of action and peak concentration | 22 min-4.5 h | 1-3 h | 1-2 h | 1-2 h |
| Oral bioavailability | 3%-7% | 66% (fasting); 80%-100% (with food) | 50%; prolonged absorption | 62% |
| Half-life | 12-17 h | 5-9 h | 8-12 h | 10-14 h |
| Plasma protein binding | 92%-95% | 87% | 99% | 55% |
| Metabolism | Conjugation, prodrug is P-gp substrate | CYP3A4/5, CYP2J2, hydrolysis, and P-gp substrate | CYP3A4 (major), CYP1A2, 2C8, 2C19, 2J2 (all minor), and P-gp substrate | Conjugation, hydrolysis, CYP3A4 (all minor), and P-gp substrate |
| Elimination | Renal (80%) | Renal (66%), fecal (7%), and unchanged (36%) | Renal (27%), fecal (56%), and biliary (minimal) | Renal (50%), metabolism and biliary/intestinal excretion (50%) |
| Absorption | Lower gastric region and duodenum | Primarily proximal small intestine and some gastric absorption | Primarily proximal small intestine and some gastric absorption | Primarily proximal small intestine and some gastric absorption |
| Antidote | Idarucizumab∗ | Andexanet-α∗ | Andexanet-α∗ | Andexanet-α∗ |
| Other options for overdose | Hemodialysis and gastric lavage with charcoal (within 2 h of consumption) | PCC (3 or 4 factor) | PCC (3 or 4 factor) | PCC (3 or 4 factor) and TXA |
| Food interaction | None | None | None | None |
| Drug interactions that increase drug levels | Amiodarone, quinidine, azole antifungals (eg, ketoconazole), and ritonavir proton pump inhibitor | Azole antifungals (eg, ketoconazole), all HIV protease inhibitors (eg, ritonavir), and clarithromycin | Azole antifungals (eg, ketoconazole), all HIV protease inhibitors (eg, ritonavir), and clarithromycin | Azole antifungals (eg, ketoconazole), all HIV protease inhibitors (eg, ritonavir), and clarithromycin |
| Drug interactions that decrease drug levels | Rifampin, phenytoin, carbamazepine, and St. John’s wort | Anticonvulsants (eg, phenytoin and carbamazepine), and rifampin | Anticonvulsants (phenytoin and carbamazepine), and rifampin | Anticonvulsants (phenytoin and carbamazepine), and rifampin |
| Laboratory measurement to assess anticoagulant effect† | aPTT, TCT, and dilute TCT | PT/INR and anti–factor Xa assay (for Xa inhibitor) | PT/INR [minimal effect] and anti–factor Xa assay (for Xa inhibitor) | Anti–factor Xa assay (for Xa inhibitor) |
| Available formulations | Capsules, pellets (sprinkles), and oral solution‡ | Tablet and oral solution | Tablet and oral solution | Tablet and oral solution |
| Patient assistance program for drug | Boehringer-Ingelheim | Johnson & Johnson | Bristol Myers Squibb | No program currently available |
| Variable . | Dabigatran etexilate . | Rivaroxaban . | Apixaban∗ . | Edoxaban∗ . |
|---|---|---|---|---|
| Prodrug | Yes | No | No | No |
| Mechanism of action | Direct IIa inhibitor; inhibits clot-bound and free thrombin | Direct Xa inhibitor; inhibits clot-bound and free Xa | Direct Xa inhibitor; inhibits clot-bound and free Xa | Direct Xa inhibitor; inhibits clot-bound and free Xa |
| Time to onset of action and peak concentration | 22 min-4.5 h | 1-3 h | 1-2 h | 1-2 h |
| Oral bioavailability | 3%-7% | 66% (fasting); 80%-100% (with food) | 50%; prolonged absorption | 62% |
| Half-life | 12-17 h | 5-9 h | 8-12 h | 10-14 h |
| Plasma protein binding | 92%-95% | 87% | 99% | 55% |
| Metabolism | Conjugation, prodrug is P-gp substrate | CYP3A4/5, CYP2J2, hydrolysis, and P-gp substrate | CYP3A4 (major), CYP1A2, 2C8, 2C19, 2J2 (all minor), and P-gp substrate | Conjugation, hydrolysis, CYP3A4 (all minor), and P-gp substrate |
| Elimination | Renal (80%) | Renal (66%), fecal (7%), and unchanged (36%) | Renal (27%), fecal (56%), and biliary (minimal) | Renal (50%), metabolism and biliary/intestinal excretion (50%) |
| Absorption | Lower gastric region and duodenum | Primarily proximal small intestine and some gastric absorption | Primarily proximal small intestine and some gastric absorption | Primarily proximal small intestine and some gastric absorption |
| Antidote | Idarucizumab∗ | Andexanet-α∗ | Andexanet-α∗ | Andexanet-α∗ |
| Other options for overdose | Hemodialysis and gastric lavage with charcoal (within 2 h of consumption) | PCC (3 or 4 factor) | PCC (3 or 4 factor) | PCC (3 or 4 factor) and TXA |
| Food interaction | None | None | None | None |
| Drug interactions that increase drug levels | Amiodarone, quinidine, azole antifungals (eg, ketoconazole), and ritonavir proton pump inhibitor | Azole antifungals (eg, ketoconazole), all HIV protease inhibitors (eg, ritonavir), and clarithromycin | Azole antifungals (eg, ketoconazole), all HIV protease inhibitors (eg, ritonavir), and clarithromycin | Azole antifungals (eg, ketoconazole), all HIV protease inhibitors (eg, ritonavir), and clarithromycin |
| Drug interactions that decrease drug levels | Rifampin, phenytoin, carbamazepine, and St. John’s wort | Anticonvulsants (eg, phenytoin and carbamazepine), and rifampin | Anticonvulsants (phenytoin and carbamazepine), and rifampin | Anticonvulsants (phenytoin and carbamazepine), and rifampin |
| Laboratory measurement to assess anticoagulant effect† | aPTT, TCT, and dilute TCT | PT/INR and anti–factor Xa assay (for Xa inhibitor) | PT/INR [minimal effect] and anti–factor Xa assay (for Xa inhibitor) | Anti–factor Xa assay (for Xa inhibitor) |
| Available formulations | Capsules, pellets (sprinkles), and oral solution‡ | Tablet and oral solution | Tablet and oral solution | Tablet and oral solution |
| Patient assistance program for drug | Boehringer-Ingelheim | Johnson & Johnson | Bristol Myers Squibb | No program currently available |
aPTT, activated partial thromboplastin time; dTCT, diluted thrombin clotting time; PCC, prothrombin complex concentrates; PT/INR, prothrombin time/international normalized ratio; TCT, thrombin clotting time; TXA, tranexamic acid.
Not approved by the US Food and Drugs Administration for children.
Routine monitoring of anticoagulant effect is not required.
Not approved for infants aged <3 mo.