The authors have noticed a few errors in Table 1 and would therefore correct these points.
If in vivo human studies show evidence of a ≤2 times increase in area under the curve (AUC) exposure for inhibitors or ≤ 20% decrease in exposure for inducers.
Table 1Practical Recommendations for Drug-Drug Interactions Management with DOACs
| Dabigatran | Rivaroxaban | Apixaban | Edoxaban | |
|---|---|---|---|---|
| Strong P-gp inhibitor only | Association not recommended (unless proven otherwise) -> consider VKA as a first-line treatment or if possible change the perpetrator to a non-interacting molecule | |||
| Strong CYP3A/5 inhibitor only or combined P-gp/CYP3A4/5 inhibitor | OK | Association not recommended (unless proven otherwise) -> consider VKA as a first-line treatment or if possible change the perpetrator to a non-interacting molecule | OK | |
| Moderate to Weak P-gp inhibitor only | Use with caution Weigh risk-to-benefit ratio or consider VKA as a first-line treatment if ≥2 risk factors or if CL<30 mL/min | |||
| Moderate to Weak CYP3A4/5 inhibitor only | OK | Use with caution Weigh risk-to-benefit or consider VKA as a first-line treatment if ≥2 risk factors or if CL<30 mL/min | OK | |
| CYP3A4/5 or combined P-gp/ CYP3A4/5 inducer | Association not recommended‡ (unless proven otherwise) -> consider VKA as a first-line treatment or if possible change the perpetrator to a non-interacting molecule | |||
CL = clearance; DOACs = direct oral anticoagulants; VKA = vitamin K antagonists.
† Risk factors: renal failure (CL <50 mL/min according to Cockroft-Gault equation), weight <60 kg, advanced age (>80 years), additional P-gp or CYP3A4/5 inhibitor. Classification of inhibitors/inducers according to the Food & Drug Administration.13
‡ Combination with dabigatran and edoxaban is acceptable with a strong 3A4/5 inhibitor or inductor only and NOT with a combined 3A4/5/P-gp inhibitor/inductor with a strong inhibitory/induction activity against P-gp.
In Table 1, in the rows for “strong 3A4/5 inhibitor only and combined 3A4/5/P-gp inhibitor” and "CYP3A4/5 or combined P-gp/ CYP3A4/5 inducer", combination with dabigatran and edoxaban is acceptable with a strong 3A4/5 inhibitor or inductor only and NOT with combined 3A4/5/P-gp inhibitor/inductor with a strong inhibition/induction activity against the P-gp. We added a commentary below the table.
We also noticed an error in the web page of Table 1 (NOT present in the pdf version). The moderate to weak CYP3A4/5 inhibitor should be used with caution with apixaban AND rivaroxaban.
Finally, a 1 should be replaced by a * in the row of the inducers.
We are providing the correct and modified version of the table below:
The publisher would like to apologise for any inconvenience caused.
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Published online: November 22, 2022
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- Drug-Drug Interactions with Direct Oral Anticoagulants: Practical Recommendations for CliniciansThe American Journal of MedicineVol. 134Issue 8
- PreviewCurrent guidelines from the European Society of Cardiology and American Heart Association widely recommend direct oral anticoagulants (DOACs) instead of vitamin K antagonists (VKAs) in the vast majority of patients with nonvalvular atrial fibrillation.1,2 In theory, DOACs do not require routine monitoring because of their stable pharmacological profiles compared with VKAs.3 However, when they are used in real-world conditions and outside the stringent framework of clinical trials, substantial interindividual variations in dose-concentration response are observed, leading to consider dose adjustment outside the standard risk groups.
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