Pharmacy World & Science

, Volume 31, Issue 2, pp 224–229 | Cite as

Retrospective assessment of potential interaction between levofloxacin and warfarin

  • Gabriel Mercadal OrfilaEmail author
  • Berta Gracia García
  • Elisabet Leiva Badosa
  • María Perayre Badía
  • Concepción Reynaldo Martínez
  • Ramón Jodar Masanés
Research Article


Objective There is currently a controversy regarding interactions between levofloxacin and warfarin. The aim of this study was to determine the clinical relevance of this interaction in our setting. Setting A university hospital in Barcelona, Spain. Methods We carried out a retrospective evaluation of all patients hospitalized in our hospital during the period 2000–2005, selecting all those concomitantly treated with levofloxacin and warfarin for the study. The following data were compiled: demographic information, concomitant medication, comorbid conditions, and relevant analytical parameters, particularly the international normalized ratio (INR), including values taken before, during, and after concomitant administration of the two study drugs. Patients for whom INR values during concomitant administration were not available were excluded. Differences in INR before and during the potential interaction, and before and after the interaction were analyzed with the Wilcoxon t test using SPSS (V12.0). In addition, patients were stratified according to presence or not of toxic habits (smoking/alcohol consumption) to investigate the possible impact of these factors on the interaction under study. Results Among the 30 patients identified, 9 were excluded because INR data during concomitant administration of warfarin and levofloxacin were not available. Statistical analysis demonstrated significant increase in INR (P = 0.001) following addition of levofloxacin to warfarin therapy. Conclusions. The results of this study reaffirm the hypothesis that concomitant administration of levofloxacin and warfarin leads to INR increase; hence close monitoring of INR is advisable when patients are prescribed this combination of drugs.


Drug interaction Levofloxacin Quinolones Warfarin 



The authors would like to thank Celine Cavallo for her linguistic advice.


No financial relationships to disclose.

Conflict of Interest



  1. 1.
    Consejo General de Colegios Oficiales de Farmacéuticos. Catálogo de especialidades Famacéuticas; 2006.Google Scholar
  2. 2.
    Levofloxacin. DRUGDEX System. Greenwood Village, CO: Thomson Micromedex, expires; 2008 Dec 31. Accessed 21 Dec 2007.Google Scholar
  3. 3.
    Gobernado M, Salavert M, Santos M, Cantón E, Pastor A, Roma E. Quinolonas. In: Antimicrobianos en medicina, editor. Sociedad Española de Quimioterapia. Barcelona: Prous Science S.A.; 1999. p. 383–416.Google Scholar
  4. 4.
    Hirsh J, Dalen JE, Anderson DR, Poller L. Oral anticoagulants: mechanisms of action, clinical effectiveness, and optimal therapeutic range. Chest. 2001;119:8S–21S. doi: 10.1378/chest.119.1_suppl.8S.PubMedCrossRefGoogle Scholar
  5. 5.
    Schentag JJ, Welage LS, Grasela TH, Adelman MH. Determinants of antibiotic-associated hypoprothrombinemia. Pharmacotherapy. 1987;3:80–6.Google Scholar
  6. 6.
    Jolson HM, Tanner LA, Green L, Grasela TH. Adverse reaction reporting of interaction between warfarin and fluoroquinolones. Arch Intern Med. 1991;151:1003–4. doi: 10.1001/archinte.151.5.1003.PubMedCrossRefGoogle Scholar
  7. 7.
    Lipsky JJ. Antibiotic-associated hypothrombinaemia. J Antimicrob Chemother. 1988;21:281–300. doi: 10.1093/jac/21.3.281.PubMedCrossRefGoogle Scholar
  8. 8.
    Ravnan SL, Locke C. Levofloxacin and warfarin interaction. Pharmacotherapy. 2001;21:884–5. doi: 10.1592/phco.21.9.884.34559.PubMedCrossRefGoogle Scholar
  9. 9.
    Gheno G, Cinetto L. Levofloxacin-warfarin interaction. Eur J Clin Pharmacol. 2001;57:427. letter. doi: 10.1007/s002280100335.
  10. 10.
    Jones CB, Fugate SE. Levofloxacin and warfarin interaction. Ann Pharmacother. 2002;36:1554–7. doi: 10.1345/aph.1C074.PubMedCrossRefGoogle Scholar
  11. 11.
    Mercadal G, Badía MB, Llop JM, Fort E, Reynaldo C, Jodar R. Potential drug interaction between levofloxacin and warfarin: 3 case reports. Eur J Hosp Pharm. 2005;11:74–7.Google Scholar
  12. 12.
    Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41:674–80. doi: 10.1345/aph.1H423.PubMedCrossRefGoogle Scholar
  13. 13.
    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. doi: 10.1177/009127009603601111.PubMedCrossRefGoogle Scholar
  14. 14.
    Yamreudeewong W, Lower DL, Kilpatrick DM, Enlow AM, Burrows MM, Greenwood MC. Effect of levofloxacin coadministration on the international normalized ratios during warfarin therapy. Pharmacotherapy. 2003;23:333–8. doi: 10.1592/phco.23.3.333.32101.PubMedCrossRefGoogle Scholar
  15. 15.
    McCall KL, Scott JC, Anderson HG. Retrospective evaluation of a possible interaction between warfarin and levofloxacin. Pharmacotherapy. 2005;25:67–73. doi: 10.1592/phco. Scholar
  16. 16.
    Vadlamudi RS, Smalligan RD, Ismail HM. Interaction between warfarin and levofloxacin: case series. South Med J. 2007;100:720–4.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Gabriel Mercadal Orfila
    • 1
    • 2
    Email author
  • Berta Gracia García
    • 1
  • Elisabet Leiva Badosa
    • 1
  • María Perayre Badía
    • 1
  • Concepción Reynaldo Martínez
    • 3
  • Ramón Jodar Masanés
    • 1
  1. 1.Pharmacy DepartmentHospital Universitari de BellvitgeBarcelonaSpain
  2. 2.Servicio de FarmaciaHospital Mateu OrfilaMenorcaSpain
  3. 3.Hematology DepartmentHospital Universitari de BellvitgeBarcelonaSpain

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