Warfarin and ciprofloxacin interaction: case report and controversy.

Warfarin is a potent anticoagulant that acts by interfering with hepatic synthesis of vitamin Kdependent clotting factors (II, VII, IX, and X).I,2 Bleeding is the primary complication of warfarin therapy.3 A variety of drugs, including many antimicrobial agents, can increase the anticoagulant effect of warfarin.,4 Ciprofloxacin is one antibiotic reported to influence the effect of warfarin.s1o Ciprofloxacin is a synthetic fluoroquinolone with a broad antimicrobial spectrum. II Fluoroquinolones have been reported to enhance the effect of warfarin, and appropriate laboratory tests should be routinely monitored. 12 The exact mechanism of the warfarin-ciprofloxacin interaction is unknown. Ciprofloxacin is postulated to affect gut flora, displace warfarin from albumin, and interfere with hepatic metabolism by inhibiting the cytochrome P-450 enzyme system. 13,14 Conflicting information exists between case reports and clinical studies on the validity of the warfarin-ciprofloxacin interaction. A review of case reports submitted to the Food and Drug Administration in 1991 concluded the warfarin-fluoroquinolone interaction is clinically important and prompted recommendations for revisions in product labeling.13 Another review concluded the warfarinciprofloxacin interaction was probable.4 Yet, two clinical studies of this interaction found no notable changes in prothrombin time or international normalized ratio (INR), and no documented bleeding events. These authors concluded that a warfarin-