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A case series of the rifampin-warfarin drug interaction: focus on practical warfarin management

  • Pharmacodynamics
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To provide practical guidance by providing weekly descriptions of warfarin requirements for the onset and offset of the rifampin-warfarin interaction.

Methods

A retrospective chart review within an outpatient Anticoagulation Clinic (AC). Patients were eligible for the onset phase provided they had known ambulatory-based warfarin steady-state requirements prior to rifampin initiation. For the offset phase, warfarin must be managed by the AC following rifampin discontinuation. Each phase was described separately with warfarin proportionate dose changes (median, IQR) for weeks 1, 2, and 4 as well as the change required to reach warfarin steady state.

Results

Ten patients with 11 courses of warfarin-rifampin were included. For onset, clinicians should anticipate proportionate warfarin dose increases of 30–80% from week 1 to week 2 and a further 20–100% from week 2 to 4, with an overall warfarin dose increase of 165% (IQR 99, 227) to reach steady state at 30 days. For offset, clinicians should anticipate proportionate warfarin dose decreases of 15–25% for both week 1 and 2, and a further 20% for both week 3 and 4, resulting in an overall warfarin decrease of 67% (IQR − 70, − 58) to reach steady state at 4 weeks for most patients.

Conclusion

Close monitoring with at least twice weekly INRs for weeks 1 to 2 of both phases is needed to respond to substantially changing warfarin dose requirements. While inter- and intra-patient variability for proportionate warfarin dose changes for both the onset and offset of this drug interaction exists, our data provides general guidance.

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References

  1. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G (2008) Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 133(6 Suppl):160S–198S

    Article  CAS  Google Scholar 

  2. Julia S, James U (2017) Direct oral anticoagulants: a quick guide. European cardiology 12(1):40–45

    Article  Google Scholar 

  3. Yeh C, Hogg K, Weitz J (2015) Overview of the new oral anticoagulants: opportunities and challenges. Arteriosclerosis, Thrombosis, and Vascular Biology 35(5):1056–1065

    Article  CAS  Google Scholar 

  4. Foerster KI, Hermann S, Mikus G, Haefeli WE (2020) Drug-drug interactions with direct oral anticoagulants. Clin Pharmacokinet

  5. Nutescu EA, Shapiro NL, Ibrahim S, West P Warfarin and its interactions with foods, herbs and other dietary supplements. Expert Opin Drug Saf 2006;5(3):433–451

  6. Bungard TJ, Yakiwchuk E, Foisy M, Brocklebank C (2011) Drug interactions involving warfarin: practice tool and practical management tips. Canadian Pharmacists Journal / Revue des Pharmaciens du Canada 144(1):21–25.e9

    Article  Google Scholar 

  7. Kim S, Kang J, Hartman J et al (2013) Metabolism of R- and S-warfarin by CYP2C19 into four hydroxywarfarins. Drug Metabolism Letters 6(3):157–164

    Article  Google Scholar 

  8. Kaminsky LS, Zhang Z-Y (1997) Human P450 metabolism of warfarin. Pharmacol Ther 73(1):67–74

    Article  CAS  Google Scholar 

  9. LiverTox: Clinical and research information on drug-induced liver injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. https://www.ncbi.nlm.nih.gov/books/NBK547852/, Accessed May 10, 2020

  10. Acocella G (1978) Clinical pharmacokinetics of rifampicin. Clinical pharmacokinetics 3(2):108–127

    Article  CAS  Google Scholar 

  11. Romankiewicz JA, Ehrman M (1975) Rifampin and warfarin: a drug interaction. Annals of internal medicine 82(2):224

    Article  CAS  Google Scholar 

  12. Self TH, Mann RB (1975) Interaction of rifampin and warfarin. Chest 67(4):490–491

    Article  CAS  Google Scholar 

  13. Almog S, Martinowitz U, Halkin H et al (1988) Complex interaction of rifampin and warfarin. Southern medical journal 81(10):1304–1306

    Article  CAS  Google Scholar 

  14. Lee CR, Thrasher KA (2001) Difficulties in anticoagulation management during coadministration of warfarin and rifampin. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 21(10):1240–1246

    Article  CAS  Google Scholar 

  15. Kim KY, Epplen K, Foruhari F, Alexandropoulos H (2007) Update on the interaction of rifampin and warfarin. Prog Cardiovasc Nurs 22(2):97–100

    Article  Google Scholar 

  16. Krajewski KC (2010) Inability to achieve a therapeutic INR value while on concurrent warfarin and rifampin. The Journal of Clinical Pharmacology 50(6):710–713

    Article  CAS  Google Scholar 

  17. Casner PR (1996) Inability to attain oral anticoagulation: warfarin-rifampin interaction revisited. Southern medical journal 89(12):1200–1203

    Article  CAS  Google Scholar 

  18. Martins MAP, Reis AMM, Sales MF et al (2013) Rifampicin-warfarin interaction leading to macroscopic hematuria: a case report and review of the literature. BMC pharmacology & toxicology 14(1):27

    Article  Google Scholar 

  19. Fahmi AM, Abdelsamad O, Elewa H (2016) Rifampin-warfarin interaction in a mitral valve replacement patient receiving rifampin for infective endocarditis: a case report. SpringerPlus. 5(1):8

    Article  Google Scholar 

  20. Maina M, Pastakia S, Manji I, Kirui N, Kirwa C, Karwa R (2013) Describing the profile of patients on concurrent rifampin and warfarin therapy in western kenya: a case series. Drugs R D 13(3):191–197

    Article  CAS  Google Scholar 

  21. Poon M, Moffett BS, Yee DL (2017) Warfarin-rifampin drug interaction in a pediatric patient. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 22(5):375–377

    Article  Google Scholar 

  22. Warfarin: Common Causes and Management Strategies for High INRs, Thrombosis Canada, 2015 http://thrombosiscanada.ca/wp-content/uploads/2015/03/Warfarin-Causes-of-High-INRs.pdf Accessed May 15, 2020

  23. Galetin A, Burt H, Gibbons L, Houston J.B. Prediction of time-dependent CYP3A4 drug-drug interactions: impact of enzyme degradation, parallel elimination pathways, and intestinal inhibition. 2006

    Google Scholar 

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Author information

Authors and Affiliations

  1. University of Alberta, Edmonton, Alberta, Canada

    Charlotte S. Yang

  2. Pharmacy Services, Alberta Health Services, Edmonton, Alberta, Canada

    Rosaleen Boswell

  3. Division of Cardiology, University of Alberta, 8425 Aberhart Centre, 11402 University Avenue, Edmonton, AB, T6G 2J3, Canada

    Tammy J. Bungard

Authors
  1. Charlotte S. Yang
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  2. Rosaleen Boswell
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  3. Tammy J. Bungard
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Contributions

CSY contributed to the design of the work, acquisition, and interpretation of the data. She drafted the manuscript, has approved this version for publication, and is in agreement to be accountable for all aspects of the work.

RB contributed to the design and interpretation of the data. She critically revised the manuscript, has approved this version for publication, and is in agreement to be accountable for all aspects of the work.

TJB contributed to the conception, design, and interpretation of the data. She critically revised the manuscript, has approved this version for publication, and is in agreement to be accountable for all aspects of the work.

Corresponding author

Correspondence to Tammy J. Bungard.

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Conflict of interest

CSY and RB have no conflicts to declare. TJB has received unrestricted research grants from LeoPharma and Pfizer, all unrelated to this manuscript.

Ethics approval

Approved by the University of Alberta Research Ethics Board (Pro000097796).

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Yang, C.S., Boswell, R. & Bungard, T.J. A case series of the rifampin-warfarin drug interaction: focus on practical warfarin management. Eur J Clin Pharmacol 77, 341–348 (2021). https://doi.org/10.1007/s00228-020-03057-x

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  • DOI: https://doi.org/10.1007/s00228-020-03057-x

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