Skip to main content
Log in

Brief report: The risk of overanticoagulation with antibiotic use in outpatients on stable warfarin regimens

  • Original Article
  • Published:
Journal of General Internal Medicine Aims and scope Submit manuscript

Abstract

BACKGROUND: Medication interactions account for a significant proportion of overanticoagulation in warfarin users. However, little is known about the incidence or degree of interaction with commonly used oral antibiotics.

OBJECTIVE: To investigate the incidence and degree of overanticoagulation associated with commonly used oral antibiotics.

DESIGN: Retrospective cohort study of patients using warfarin who initiated an antibiotic (azithromycin, levofloxacin, or trimethoprim/sulfamethoxazole (TMP/SMX)) or terazosin for clinical indications between January 1998 and December 2002. The incidence of international normalized ratio (INR) elevation and the degree of change and bleeding events after institution of either medication type was recorded.

SUBJECTS: Patients at a university-affiliated Veteran’s Affairs Medical Center.

RESULTS: The mean change in INR was −0.15 for terazosin, 0.51 for azithromycin, 0.85 for levofloxacin, and 1.76 for TMP/SMX. These mean INR changes in the antibiotic groups were all statistically different from the terazosin group. The incidence of supratherapeutic INR was 5% for terazosin, 31% for azithromycin, 33% for levofloxacin, and 69% for TMP/SMX. The incidence of absolute INR >4.0 was 0% for terazosin, 16% for azithromycin, 19% for levofloxacin, and 44% for TMP/SMX.

CONCLUSIONS: Among acutely ill outpatients, oral antibiotics (azithromycin, levofloxacin, and TMP/SMX) increase the incidence and degree of overanticoagulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism. Ann Intern Med. 2003;139:893–900.

    PubMed  Google Scholar 

  2. Levine MN, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant therapy. Chest. 2001;119:108S-21.

    Article  PubMed  CAS  Google Scholar 

  3. Cannegueter SC, Rosendaal FR, Wintzen AR, et al. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med. 1995;333:11–7.

    Article  Google Scholar 

  4. Glasheen JJ, Fugit RV. How warfarin interacts with common antibiotics. Emerg Med. 2004;36:30C-30I.

    Google Scholar 

  5. Wells PS, Holbrook AM, Crowther NR, Hirsh J. Interactions of warfarin with drugs and food. Ann Intern Med. 1994;121:676–83.

    PubMed  CAS  Google Scholar 

  6. Penning-van Beest FJ, Van Meegen E, Rosendaal FR, Stricker BH. Drug interactions as a cause of overanticoagulation on phenprocoumon or acenocoumarol predominantly concern antibacterial drugs. Clin Pharmacol Ther. 2001;69:451–7.

    Article  PubMed  CAS  Google Scholar 

  7. Panneerselvam S, Baglin C, Lefort W, Baglin T. Analysis of risk factors for over-anticoagulation in patients receiving long-term warfarin. Br J Hematol. 1998;103:422–4.

    Article  CAS  Google Scholar 

  8. Horton JD, Bushwick BM. Warfarin therapy: evolving strategies in anticoagulation. Am Fam Physician. 1999;59:635–46.

    PubMed  CAS  Google Scholar 

  9. Beckey NP, Parra D, Colon A. Retrospective evaluation of a potential interaction between azithromycin and warfarin in patients stabilized on warfarin. Pharmacotherapy. 2000;20:1055–9.

    Article  PubMed  CAS  Google Scholar 

  10. Tatro DS, ed. Drug Interaction Facts. St. Louis, Mo: Facts and Comparisons; 2003.

    Google Scholar 

  11. McCall KL, Anderson HG, Jones AD. Determination of the lack of a drug interaction between azithromycin and warfarin. Pharmacotherapy. 2004;24:188–94.

    Article  PubMed  CAS  Google Scholar 

  12. Rindone JP, Kuey CL, Jones WN, Garewal HS. Hypoprothrombinemic effect of warfarin not influenced by ciprofloxacin. Clin Pharm. 1991;10:136–8.

    PubMed  CAS  Google Scholar 

  13. Bianco TM, Bussey HI, Farnett LE, Linn WD, Roush MK, Wong YW. Potential warfarin-ciprofloxacin interaction in patients receiving long-term anticoagulation. Pharmacotherapy. 1992;12:435–9.

    PubMed  CAS  Google Scholar 

  14. Israel DS, Stotka J, Rock W, t al. Effect of ciprofloxacin on the pharmacokinetics and pharmacodynamics of warfarin. CID. 1996;22:251–6.

    CAS  Google Scholar 

  15. Liao S, Palmer M, Fowler C, Nayak RK. Absence of an effect of levofloxacin on warfarin pharmacokinetics and anticoagulation in male volunteers. J Clin Pharmacol. 1996;36:1072–7.

    Article  PubMed  CAS  Google Scholar 

  16. Yamreudeewong W, Lower DL, Kipatrick DM, Enlow AM, Burrows MM, Greenwood MC. Effect of levofloxacin coadministration on the international normalized ratios during warfarin therapy. Pharmacotherapy. 2003;23:333–8.

    Article  PubMed  CAS  Google Scholar 

  17. Glasheen JJ, Fugit RV, Prochazka AV. Effect of levofloxacin coadministration on the international normalized ratios during warfarin therapy—a comment. Pharmacotherapy. 2003;23:1079–80.

    Article  PubMed  Google Scholar 

  18. O’Reilly RA, Motley CH. Racemic warfarin and trimethoprim-sulfamethoxasole interaction in humans. Ann Intern Med. 1979;91:34–6.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jeffrey J. Glasheen MD.

Additional information

Drs. Glasheen, Fugit, and Prochazka have no financial disclosures, and have no conflicts of interest to report for this article or this research.

Dr. Glasheen was affiliated with the Department of Medicine. Division of General Internal Medicine, at the Denver VA Medical Center, University of Colorado Health Science Center, Denver, CO, during the data collection phase of this research.

Dr. Glasheen certifies that the has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All above-stated authors have contributed to the design, execution, analysis, and writing of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Glasheen, J.J., Fugit, R.V. & Prochazka, A.V. Brief report: The risk of overanticoagulation with antibiotic use in outpatients on stable warfarin regimens. J GEN INTERN MED 20, 653–656 (2005). https://doi.org/10.1007/s11606-005-0113-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11606-005-0113-5

Key words

Navigation