Table 1.
Dose adjustments for each direct oral anticoagulant drug in accordance with European Medicines Agency and Food and Drugs Administration guidelines16, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31
| European Medicines Agency (EMA) | Food and Drugs Administration (FDA) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Dabigatran | Rivaroxaban | Apixaban | Edoxaban | Dabigatran | Rivaroxaban | Apixaban | Edoxaban | ||
| Recommended dose | 150 mg BID | 20 mg OD | 5 mg BID | 60 mg OD | Recommended dose | 150 mg BID | 20 mg OD | 5 mg BID | 60 mg OD |
| Reduced dose | 110 mg BID | 15 mg OD | 2.5 mg BID | 30 mg OD | Reduced dose | 75 mg BID b | 15 mg OD | 2.5 mg BID | 30 mg OD |
| Dose reduction recommended: | Dose reduction recommended: | ||||||||
| Renal function | – | CrCl 15 − 50 mL/min | CrCl 15 − 29 mL/min | CrCl 15 − 50 mL/min | Renal function | CrCl 15 − 30 mL/min | CrCl 15 − 50 mL/min | Scr ≥ 1.5 mg/dLa or under dialysisb | CrCl 15 − 50 mL/min |
| Scr ≥ 1.5 mg/dLa | |||||||||
| Older age | ≥ 80 y | – | ≥ 80 ya | – | |||||
| Body weight | – | – | ≤ 60 kga | ≤ 60 kg | P‐gp inhibitors |
‐ In patients with CrCl < 30 mL/min: Not recommended ‐ In patients with CrCl 30–50 mL/min: Reduce dose or avoid |
– | Use should be avoided (Also with strong CYP3A4 inhibitors) | – |
| P‐gp inhibitors | Example: Verapamil | – | – | Ciclosporin, dronedaron, eritromicin, cetoconazol | |||||
| Additional conditions when dose reduction need to be considered: | Older age | – | – | ≥ 80 ya | – | ||||
| Older age | 75 − 80 y | – | – | – | |||||
| Renal function | CrCl 30 − 50 mL/min | – | – | – | Body weight | – | – | ≤ 60 kga | – |
| Increased bleeding risk | Patients with gastritis, esophagitis or gastroesophageal reflux | – | – | – | Increased bleeding risk | – | – | – | – |
| Contraindicated | CrCl < 30 mL/min | CrCl < 15 mL/min | No clinical experience in patients with CrCl < 15 mL/min or under dialysis | CrCl < 15 mL/min or under dialysis | Not recommended | CrCl < 15 mL/min | CrCl < 15 mL/min | – | CrCl > 95 mL/minc |
For apixaban 2 of these 3 conditions are required to reduce the dose.
The reduced dose authorization and use in special populations was based on pharmacokinetic data.
This black box warning suggests the use of another anticoagulant for patients with CrCl >95 mL/min and was based on the reported higher rates of ischaemic stroke of these patients.
BID = twice‐a‐day; OD = once‐daily; CrCl = creatinine clearance; y = years; P‐gp = P‐ glycoprotein.