Abstract 684: Preemptive Warfarin Dose Reduction Effectively Maintains Therapeutic Anticoagulation After Initiation of Trimethoprim-Sulafamethoxazole or Levofloxacin
Background: Antibiotics (abx) are well known for their ability to potentiate warfarin (warf) anticoagulation. While preemptive warf dose reduction (DR) upon initiation of abx has been advocated by some experts, there are no published data regarding the efficacy of this strategy vs. the alternative strategy of not changing warf dose and carefully following international normalized ratio (INR) results. In this study we compared preemptive warf DR of 10 –20 % vs. no change in warf dosing for managing chronically anticoagulated patients (pts) upon initiation of either trimethoprim-sulfamethoxazole (TMP-SMX) or levofloxacin (levo).
Methods and Results: Forty pts who were prescribed either TMP-SMX or levo while taking warf were retrospectively identified. Of these, 18 pts received preemptive warf DR (8 pts received TMP-SMX and 10 received levo), and 22 pts underwent no change in warf dosing (control group; 9 pts received TMP-SMX, 13 pts received levo). There was no difference between the DR and control groups in the mean value of the most recent INR before beginning abx therapy (2.53 ± 0.12 vs. 2.52 ± 0.11;P > 0.9). Pts in the DR group underwent 16.0 ± 1.2% reduction in weekly warf dose (16.2% for levo pts vs 16.3% for TMP-SMX pts, P = 0.473). Mean interval between initiation of abx and next INR was 5.1 ± 0.4 vs. 4.7 ± 0.5 days for DR vs. control pts, respectively (P > 0.5). For the DR group the mean post-abx INR did not differ significantly from the mean pre-abx INR. In contrast, for pts in the control group, the mean post-abx INR (5.27 ± 0.7) was significantly greater than both the corresponding pre-abx INR (2.52 ± 0.11;P < 0.001) and the post-abx INR of the DR group (2.75 ± 0.27;P < 0.003). With respect to clinical outcomes, 2 pts (11%) in the DR group required transient interruption of warf dosing because the post-abx INR result was supratherapeutic. In contrast, 12 pts (55%) within the control group required transient warf dose interruption because of a supra-therapeutic post-abx INR (P = 0.007 vs. DR group).
Conclusions: An approximately 15% decrease in warf dose can be a very effective strategy for maintaining a therapeutic level of anticoagulation in chronically anticoagulated pts initiating treatment with TMP-SMX or levo.