Table 1. Characteristics of oral anticoagulants2,3.
| Warfarin | Direct-acting oral anticoagulants (DOACs) | |||
|---|---|---|---|---|
| Apixaban | Rivaroxaban | Dabigatran [NB1] | ||
| Mechanism of action | Competitive inhibitor of vitamin K epoxide reductase | Reversibly binding to the active site of factor Xa | Reversibly binding to the active site of factor Xa | Reversibly binding to the catalytic site of free and clot-bound factor IIa (thrombin) |
| Dosing frequency for AF [NB2] | Once daily | Twice daily | Once daily | Twice daily |
| Dosing frequency for VTE [NB2] | Once daily | Twice daily (higher dose for first 7 days) | Twice daily for 21 days then once daily | Twice daily (following 5 days of parenteral anticoagulant) |
| Elimination half-life in healthy adults [NB3] | 40 hours | 10 hours | 7 hours | 14 hours |
| Drug metabolism and transport pathways (examples of medicines inducing or inhibiting them) | CYP2C9, CYP3A enzymes (rifampicin, carbamazepine, ritonavir, fluconazole) | CYP3A enzymes, P-glycoprotein transporter (rifampicin, carbamazepine, ritonavir, ciclosporin, verapamil) | CYP3A enzymes, P-glycoprotein transporter (rifampicin, carbamazepine, ritonavir, ciclosporin, verapamil) | P-glycoprotein transporter (rifampicin, carbamazepine, ritonavir, ciclosporin, verapamil)[NB1] |
| Key advantages compared with other oral anticoagulants | Readily available anticoagulation intensity biomarker (INR) for dose adjustment Established safety in breastfeeding |
May have lowest bleeding risk in severe chronic kidney disease Standard doses sufficient for BMI over 35 kg/m2 or actual body weight over 120 kg |
Standard doses sufficient for BMI over 35 kg/m2 or actual body weight over 120 kg Once-daily dosing |
Readily available anticoagulation intensity biomarker (TCT) for detecting presence of anticoagulant |
| Key disadvantages compared with other oral anticoagulants | Routine periodic INR monitoring required Higher risk of intracranial haemorrhage Subject to more drug interactions |
Twice-daily dosing may reduce adherence Anticoagulant concentrations exceed safety threshold in breastmilk |
Doses of 15 mg and above need to be taken with food for optimal oral bioavailability | Twice-daily dosing may reduce adherence Higher risk of anticoagulant accumulation with acute kidney injury compared with other DOACs Unclear if standard doses are sufficient for BMI over 35 kg/m2 or actual body weight over120 kg |
| Antidote | Phytomenadione (vitamin K) | Andexanet alfa [NB4] | Andexanet alfa [NB4] | Idarucizumab [NB4] |
AF = atrial fibrillation; BMI = body mass index; CYP = cytochrome P450; INR = international normalised ratio; TCT = thrombin clotting time; VTE = venous thromboembolism
NB1: Dabigatran is formulated as the prodrug dabigatran etexilate, which is metabolised to the anticoagulant dabigatran after absorption. The prodrug, but not dabigatran, is subject to P-glycoprotein transport.
NB2: Specifics regarding dosing amounts, including dose adjustment for renal impairment and drug interactions, can be found in resources such as the approved product information and the Australian Medicines Handbook.
NB3: Half-lives of DOACs are significantly longer in the setting of renal impairment.
NB4: The antidotes for DOACs have a limited role for reversal of anticoagulation in emergency situations.3 Refer to ‘Management of bleeding in patients taking a DOAC’, below, for details of their indications and risks.