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Erratum to ‘Drug-Drug Interactions with Direct Oral Anticoagulants: Practical Recommendations for Clinicians’ The American Journal of Medicine Volume 134, Issue 8 (2021) 939-942

  • Jean Terrier
    Correspondence
    Requests for reprints should be addressed to Dr Jean Terrier, Clinical Pharmacology and Toxicology Division, Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine Department, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
    Affiliations
    Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland

    Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Clinical Pharmacology and Toxicology Division, Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine Department, Geneva University Hospitals, Geneva, Switzerland
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  • Frederic Gaspar
    Affiliations
    Center for Research and Innovation in Clinical Pharmaceutical Sciences, University Hospital and University of Lausanne, Lausanne, Switzerland

    School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland

    Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Switzerland
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  • Pierre Fontana
    Affiliations
    Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Division of Angiology and Hemostasis, Geneva University Hospitals, Geneva, Switzerland
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  • Youssef Daali
    Affiliations
    Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Clinical Pharmacology and Toxicology Division, Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine Department, Geneva University Hospitals, Geneva, Switzerland
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  • Jean-Luc Reny
    Affiliations
    Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland

    Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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  • Chantal Csajka
    Affiliations
    Center for Research and Innovation in Clinical Pharmaceutical Sciences, University Hospital and University of Lausanne, Lausanne, Switzerland

    School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland

    Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Switzerland
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  • Caroline F. Samer
    Affiliations
    Clinical Pharmacology and Toxicology Division, Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine Department, Geneva University Hospitals, Geneva, Switzerland
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Published:November 22, 2022DOI:https://doi.org/10.1016/j.amjmed.2022.11.001
      The authors have noticed a few errors in Table 1 and would therefore correct these points.
      Table 1Practical Recommendations for Drug-Drug Interactions Management with DOACs
      DabigatranRivaroxabanApixabanEdoxaban
      Strong P-gp inhibitor onlyAssociation not recommended (unless proven otherwise
      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.
      )

      -> 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
      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.
      Association not recommended (unless proven otherwise
      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.
      )

      -> consider VKA as a first-line treatment or if possible change the perpetrator to a non-interacting molecule
      OK
      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.
      Moderate to Weak P-gp inhibitor onlyUse with caution

      Weigh risk-to-benefit ratio or consider VKA as a first-line treatment if ≥2 risk factors
      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
       or if CL<30 mL/min
      Moderate to Weak CYP3A4/5 inhibitor onlyOKUse with caution

      Weigh risk-to-benefit or consider VKA as a first-line treatment if ≥2 risk factors
      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
       or if CL<30 mL/min
      OK
      CYP3A4/5 or combined P-gp/ CYP3A4/5 inducerAssociation not recommended (unless proven otherwise
      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.
      )

      -> 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.
      low asterisk 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.
      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.

      Linked Article

      • Drug-Drug Interactions with Direct Oral Anticoagulants: Practical Recommendations for Clinicians
        The American Journal of MedicineVol. 134Issue 8
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          Current 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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