The risk of overanticoagulation with antibiotic use in outpatients on stable warfarin regimens

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Internal Medicine

Background:

• Medication interactions are a major cause of overanticoagulation in warfarin users.
• The impact of common oral antibiotics on warfarin therapy is not well understood.

Purpose of the Study:

• To determine the incidence and severity of overanticoagulation associated with commonly prescribed oral antibiotics.
• To compare the effects of azithromycin, levofloxacin, and trimethoprim/sulfamethoxazole (TMP/SMX) on warfarin's anticoagulant effect.

Main Methods:

• A retrospective cohort study was conducted involving patients using warfarin.
• Data were collected on patients who started azithromycin, levofloxacin, TMP/SMX, or terazosin between 1998 and 2002.
• International Normalized Ratio (INR) changes, supratherapeutic INR events, and bleeding complications were recorded.

Main Results:

• Trimethoprim/sulfamethoxazole (TMP/SMX) showed the highest mean INR increase (1.76), followed by levofloxacin (0.85) and azithromycin (0.51).
• The incidence of supratherapeutic INR (>4.0) was significantly higher with antibiotics: 69% for TMP/SMX, 33% for levofloxacin, and 31% for azithromycin, compared to 5% for terazosin.
• Forty-four percent of patients on TMP/SMX experienced an INR >4.0, compared to 19% on levofloxacin and 16% on azithromycin.

Conclusions:

• Commonly used oral antibiotics, including azithromycin, levofloxacin, and TMP/SMX, are associated with increased incidence and degree of overanticoagulation in warfarin patients.
• These findings highlight the importance of monitoring INR closely when initiating oral antibiotics in patients on warfarin therapy.