Effect of Ciprofloxacin on the Pharmacokinetics and Pharmacodynamics of Warfarin

To determine if ciprofloxacin therapy alters the response to warfarin treatment, 36 adult patients attending three university-affiliated outpatient anticoagulation clinics randomly received a 12-day course of ciprofloxacin (750 mg twice daily) and a 12-day course of placebo; each course was separated by a 2-week washout period. Prothrombin times (PTs), concentrations of S-warfarin and R-warfarin (the isomers of warfarin), and concentrations of clotting factors II and VII were determined three times weekly for 9 weeks. By day 12 of ciprofloxacin therapy, concentrations of S-warfarin remained unchanged compared with those after placebo therapy, but R-warfarin concentrations increased significantly (1.15 times those after placebo therapy; P = .001); concentrations of clotting factors II and VII decreased (0.903 and 0.872 times those after placebo therapy, respectively, P < or = .020). The mean PT ratio after 12 days of ciprofloxacin therapy increased slightly (1.032 times that after placebo therapy; P = .057), but no patient had bleeding or a change in PT that required alteration in warfarin or ciprofloxacin therapy. We conclude that warfarin therapy is not a contraindication to the use of ciprofloxacin.