Document Detail

Impact of preemptive warfarin dose reduction on anticoagulation after initiation of trimethoprim-sulfamethoxazole or levofloxacin.
MedLine Citation:
PMID:  17985084     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Antibiotics can potentiate warfarin anticoagulation. While preemptive warfarin dose reduction (DR) upon initiation of antibiotics has been advocated by experts, there are no published data regarding the efficacy of this strategy vs. the conventional strategy of not changing warfarin dose and carefully following international normalized ratio (INR) results. METHODS AND RESULTS: We compared the efficacy of preemptive 10-20% DR vs. no change in warfarin dosing in 40 chronically anticoagulated patients initiating trimethoprim-sulfamethoxazole (TMP-SMX) or levofloxacin. Eighteen patients received preemptive warfarin DR and 22 control patients underwent no change in warfarin dosing. There was no difference between the DR and control groups in the mean INR before beginning antibiotic therapy (2.53 +/- 0.12 vs. 2.52 +/- 0.11; P > 0.9). Mean interval between initiation of antibiotic and next INR was 5.1 +/- 0.4 vs. 4.7 +/- 0.5 days for DR vs. control patients, respectively (P > 0.5). For both TMP-SMX and levofloxacin, patients managed with a preemptive warfarin DR strategy did not exhibit a statistically significant change in the INR after initiating antibiotic therapy. In contrast, for each antibiotic, control group patients exhibited a significant increase in mean post-antibiotic INR compared to mean pre-antibiotic INR, though the effect was more pronounced in patients treated with TMP-SMX than with levofloxacin. Of DR group patients who were treated with TMP-SMX, none (0/8) developed a subtherapeutic INR, while 40% (4/10) of levofloxacin-treated patients developed a sub-therapeutic INR. Supra-therapeutic INR results led to transient interruption of warfarin dosing in 2 patients (11%) in the DR group vs. 12 patients (55%) in the control group (P = 0.007). CONCLUSIONS: Prophylactic warfarin DR of 10-20% is effective in maintaining therapeutic anticoagulation in patients initiating TMP-SMX. An expectant strategy consisting of no change in warfarin dosing with short-term INR follow-up appears reasonable in patients treated with levofloxacin.
Abrar Ahmed; John C Stephens; Carol A Kaus; William P Fay
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article     Date:  2007-11-06
Journal Detail:
Title:  Journal of thrombosis and thrombolysis     Volume:  26     ISSN:  0929-5305     ISO Abbreviation:  J. Thromb. Thrombolysis     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-28     Completed Date:  2008-09-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502018     Medline TA:  J Thromb Thrombolysis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  44-8     Citation Subset:  IM    
Department of Internal Medicine, School of Medicine, University of Missouri-Columbia, MA406, DC043.00, One Hospital Drive, Columbia, MO 65212, USA.
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MeSH Terms
Aged, 80 and over
Anti-Infective Agents / administration & dosage*
Anticoagulants / administration & dosage*
Blood Coagulation / drug effects*
Drug Administration Schedule
Drug Interactions
Drug Monitoring
International Normalized Ratio
Middle Aged
Ofloxacin / administration & dosage*
Trimethoprim-Sulfamethoxazole Combination / administration & dosage*
Warfarin / administration & dosage*
Reg. No./Substance:
0/Anti-Infective Agents; 0/Anticoagulants; 8064-90-2/Trimethoprim-Sulfamethoxazole Combination; 81-81-2/Warfarin; 82419-36-1/Ofloxacin

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