Properties and licensed indications of NOACs
| Dabigatran | Rivaroxaban | Apixaban | Edoxaban | |
|---|---|---|---|---|
| Mechanism of action | Direct thrombin inhibitor | Factor Xa inhibitor | Factor Xa inhibitor | Factor Xa inhibitor |
| Tmax | 2 hours | 2–4 hours | 1–4 hours | 1–2 hours |
| Elimination half-life | 12–17 hours | 5–9 hours (young)11–13 hours (elderly) | 12 hours | 10–14 hours |
| P-gp re-secretion | Yes | Yes | Yes | Yes |
| CYP3A4 metabolised | No | Yes | Yes | Minimal |
| Renal excretion | Up to 80% | 66% | 25% | 35% |
| Plasma protein binding | 35% | >90% | >90% | >90% |
| Intake with food required | No | Mandatory | No | No |
| Hepatic impairment | Not recommended in patients with elevated liver enzymes (>2×ULN) | Contraindicated in hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients classified as Child-Pugh B and C. | Contraindicated in hepatic disease associated with coagulopathy and clinically relevant bleeding risk; not recommended severe hepatic impairment (Child-Pugh C); use with caution in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment or in patients with elevated liver enzymes (>2×ULN) | Contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk; not recommended In patients with severe hepatic impairment; use with caution in patients with mild to moderate hepatic impairment and patients with elevated liver enzymes (>2×ULN) |
| Antidote available | Yes | No | No | No |
| NICE approved indications and doses | ||||
| NVAF | 150 mg bd, 110 mg bd1 | 20 mg od2 | 5 mg bd3 | 60 mg od4 |
| VTE treatment and secondary prevention | 150 mg bd (following ≥5d LMWH) | 15 mg bd (initial 21 days), 20 mg od after 21 days | 10 mg bd (initial 7 days), 5 mg bd (up to 6 months); 2.5 mg bd after 6 months) | 60 mg od (following ≥5 days LMWH)4 |
| Prevention of VTE after elective hip or knee replacement | 150 mg od | 10 mg od | 2.5 mg bd | Not licensed |
| ACS | Not licensed | 2.5 mg bd | Not licensed | Not licensed |
1Dabigatran 110 mg bd dose in NVAF where ≥80 years; consider where CrCl 30–49 mL/min
2Dose reduction rivaroxaban in NVAF: 15 mg od where CrCl 30-49 mL/min
3Dose reduction apixaban in NVAF: 2.5 mg bd where CrCl 15–29 mL/min or where two of serum creatinine ≥1.5 mg/dL, age ≥80 years, body weight ≤60kg
4Dose reduction edoxaban in NVAF and VTE: 30 mg od where one of CrCl 15–49 mL/min, body weight ≤60kg, concomitant use of cyclosporin, dronedarone, erythromycin or ketoconazole
ACS = acute coronary syndrome; bd = twice per day; CrCl = creatinine clearance; LMWH = low molecular weight heparin; NICE = National Institute for Health and Care Excellence; NOAC = non-vitamin K oral anticoagulant; NVAF = non-valvular atrial fibrillation; od = once daily; P-gp = P glycoprotein; Tmax = time to peak level post ingestion; ULN = upper limit of normal; VTE = venous thromboembolism