Interactions between warfarin and three commonly prescribed fluoroquinolones.
OBJECTIVE
To critically evaluate a possible increased anticoagulant response during concomitant warfarin and fluoroquinolone therapy.


METHODS
A literature search was conducted using PubMed, International Pharmaceutical Abstracts, and MEDLINE, from inception to January 2008, combining the term warfarin individually with ciprofloxacin, levofloxacin, and moxifloxacin. These 3 quinolones were selected based on their commercial availability and use in the US.


METHODS
All publication types including human participants and published in English were eligible for review. Reports were selected based on the use of typical treatment courses of fluoroquinolones during concomitant warfarin therapy and the reporting of prothrombin time (PT) or international normalized ratio (INR).


RESULTS
Twenty-two publications were evaluated including 16 case reports or case series, 2 retrospective cohort studies, and 4 prospective studies, which included 2 placebo-controlled investigations. Identified reports covered a wide range of patient ages with multiple comorbidities. Changes in PT and INR values were considerably variable and inconsistent during concomitant warfarin and fluoroquinolone therapy. Results from the 6 structured reports demonstrated mean increases in PT and INR values that were clinically insignificant. However, some patients experienced significant increases above the desired therapeutic range. Increased anticoagulation was typically observed within the first week of concomitant fluoroquinolone therapy. Bleeding complications during times of increased anticoagulation were not always observed, but did result in death for 2 patients.


CONCLUSIONS
Published data show no consistent increase in anticoagulant effects during concomitant warfarin and 3 commonly prescribed fluoroquinolones. Therefore, more frequent monitoring during concomitant therapy would be prudent.
Carroll
Douglas N
DN
Department of Pharmacy Practice, Harrison School of Pharmacy, Auburn University, Tuscaloosa, AL 35487, USA. carrodn@auburn.edu
Carroll
Dana G
DG
D001372:Aza Compounds / Q000009:adverse effects / Q000378:metabolism*; D002939:Ciprofloxacin / Q000009:adverse effects / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods; D064704:Levofloxacin; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000009:adverse effects / Q000378:metabolism*; D011804:Quinolines / Q000009:adverse effects / Q000378:metabolism*; D014859:Warfarin / Q000009:adverse effects / Q000378:metabolism*
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D014859:Warfarin; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin