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Journal of Thrombosis and Thrombolysis

, Volume 48, Issue 3, pp 528–531 | Cite as

Carbamazepine interaction with direct oral anticoagulants: help from the laboratory for the personalized management of oral anticoagulant therapy

  • Leonardo Di Gennaro
  • Stefano Lancellotti
  • Raimondo De Cristofaro
  • Erica De CandiaEmail author
Article

Abstract

Current guidelines recommend caution in prescribing concomitant use of direct-acting oral anticoagulants (DOACs) and antiepileptic drugs due to drug–drug interactions leading to potential risk of DOACs subtherapeutic concentration and treatment failure. Herein we report a significant interaction between carbamazepine (CZP) and apixaban, causing subtherapeutic concentration of the drug in a patient with atrial fibrillation who had a transient ischemic attack (TIA) episode. Another anti-Xa DOAC, edoxaban, administered to the patient after TIA occurrence did not show significant interaction with CZP. In addition to confirm that cautions should be used when antiepileptic and DOACs are concomitantly prescribed, the present case also demonstrates that, in the management of certain subsets of patients who need anticoagulant treatment, measurement of DOAC plasma concentration can help guide a personalized management and avoid adverse clinical outcomes.

Keywords

Direct oral anticoagulant DOAC interaction Carbamazepin Anti-Xa activity Personalized oral anticoagulant therapy 

Abbreviations

NVAF

Non-valvular atrial fibrillation

CZP

Carbamazepine

INR

International normalized ratio

DOAC

Direct non-vitamin K antagonist oral anticoagulant

VKA

Vitamin-K antagonist

TIA

Transient ischemic attack

Notes

Compliance with ethical standards

Conflict of interest

The author(s) declared no conflicts of interest with respect to the authorship and/or publication of this article.

References

  1. 1.
    Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, Castella M, Diener HC, Heidbuchel H, Hendriks J, Hindricks G, Manolis AS, Oldgren J, Popescu BA, Schotten U, Van Putte B, Vardas P, Agewall S, Camm J, Baron Esquivias G, Budts W, Carerj S, Casselman F, Coca A, De Caterina R, Deftereos S, Dobrev D, Ferro JM, Filippatos G, Fitzsimons D, Gorenek B, Guenoun M, Hohnloser SH, Kolh P, Lip GY, Manolis A, McMurray J, Ponikowski P, Rosenhek R, Ruschitzka F, Savelieva I, Sharma S, Suwalski P, Tamargo JL, Taylor CJ, Van Gelder IC, Voors AA, Windecker S, Zamorano JL, Zeppenfeld K (2016) 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37:2893–2962CrossRefGoogle Scholar
  2. 2.
    Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Georg Haeusler K, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbüchel H, ESC Scientific Document Group (2018) The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary. Europace 20(8):1231–1242CrossRefGoogle Scholar
  3. 3.
    Fitzgerald JL, Howes LG (2016) Drug interactions of direct-oral anticoagulants. Drug Saf 39(9):841–845CrossRefGoogle Scholar
  4. 4.
    Lixiana: summary of products characteristics. https://www.ema.europa.eu/en/medicines/human/EPAR/lixiana#product-information-section. Accessed 8 Oct 2018
  5. 5.
    Amin A, Keshishian A, Dina O, Dhamane A, Nadkarni A, Carda E, Russ C, Rosenblatt L, Mardekian J, Yuce H, Baker CL (2019) Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population. J Thromb Thrombolysis.  https://doi.org/10.1007/s11239-019-01838-5 Google Scholar
  6. 6.
    U.S. Food and Drug Administration (2018) Drug development and drug interactions: table of substrates, inhibitors and inducers. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm. Accessed 8 Feb 2018
  7. 7.
    Giessmann T, May K, Modess C, Wegner D, Hecker U, Zschiesche M et al (2004) Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther 76:192–200CrossRefGoogle Scholar
  8. 8.
    Bortz H, Corallo CE, Tran H (2018) Increasing understanding regarding the risk of concomitant use of carbamazepine and direct oral anticoagulants. J Pharm Pract 1(89):1–3Google Scholar
  9. 9.
    Stöllberger C, Finsterer J (2017) Recurrent venous thrombosis under rivaroxaban and carbamazepine for sumptomatic epilepsy. Neurol Neurochir Pol 51:194–196CrossRefGoogle Scholar
  10. 10.
    Perlman A, Hochberg-Klein S, Choshen Cohen L, Dagan G, Hirsh-Raccah B, Horwitz E, Aldouby-Bier G, Negev T, Matok I, Azoulay L, Kalish Y, Muszkat M (2019) Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers. J Thromb Thrombolysis.  https://doi.org/10.1007/s11239-018-01804-7 Google Scholar
  11. 11.
    Bathala MS, Masumoto H, Oguma T, He L, Lowrie C, Mendell J (2012) Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans. Drug Metab Dispos 40(12):2250–2255CrossRefGoogle Scholar
  12. 12.
    Cuker A, Husseinzadeh H (2015) Laboratory measurement of the anticoagulant activity of edoxaban: a systematic review. J Thromb Thrombolysis 39(3):288–294CrossRefGoogle Scholar
  13. 13.
    Galgani A, Palleria C, Iannone LF, De Sarro G, Giorgi FS, Maschio M, Russo E (2018) Pharmacokinetic interactions of clinical interest between direct oral anticoagulants and antiepileptic drugs. Front Neurol 7(9):1067CrossRefGoogle Scholar
  14. 14.
    Stöllberger C, Finsterer J (2016) Interactions between non-vitamin K oral anticoagulants and antiepileptic drugs. Epilepsy Res 126:98–101CrossRefGoogle Scholar
  15. 15.
    Guida alla Terapia Antitrombotica, XVI edizione 2017. Raccomandazioni della Federazione dei Centri per la diagnosi della trombosi e la Sorveglianza delle terapie Antitrombotiche (FCSA)Google Scholar
  16. 16.
    De Caterina R, Ageno W, Agnelli G, Chan NC, Diener HC, Hylek E, Raskob GE, Siegal DM, Verheugt FWA, Lip GYH, Weitz JI (2019) The non-vitamin K antagonist oral anticoagulants in heart disease: section V-special situations. Thromb Haemost 119(1):14–38CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Leonardo Di Gennaro
    • 1
  • Stefano Lancellotti
    • 1
  • Raimondo De Cristofaro
    • 1
    • 2
  • Erica De Candia
    • 1
    • 2
    • 3
    Email author
  1. 1.Unità Operativa Malattie Emorragiche e Trombotiche, Area di EmatologiaFondazione Policlinico Universitario “Agostino Gemelli”, IRCCSRomeItaly
  2. 2.Istituto di Medicina Interna e GeriatriaUniversità Cattolica del Sacro CuoreRomeItaly
  3. 3.Unità Operativa Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario “Agostino Gemelli”, IRCCSIstituto di Medicina Interna e Geriatria, Università Cattolica del Sacro CuoreRomeItaly

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