Warfarin and Antibiotics: Clinical Considerations and Drug Interactions

Abstract

The administration of warfarin presents a significant difficulty in clinical practice due to the heightened risk of serious bleeding in patients, especially when used concurrently with other drugs that can alter its metabolic pathways. Antibiotics have been identified as possible drugs that can either increase or inhibit cytochrome P450-2C9, thereby affecting the efficacy of warfarin. A substantial body of evidence from multiple trials consistently indicates an increased risk of significant bleeding in individuals simultaneously undergoing antibiotic and warfarin treatment. This narrative review clarifies the complex interactions between warfarin and several kinds of antibiotics. Significant elevations in the International Normalized Ratio (INR) were found in warfarin-treated patients administered penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides. Conversely, studies have shown a decrease in INR levels in warfarin-treated patients when administered rifampin, a strong inducer of cytochrome P-450. Interestingly, cephalosporin antibiotics and amoxicillin/clavulanate, although not affecting the cytochrome P450 system, demonstrated a positive correlation with elevated INR readings. This narrative review emphasizes the necessity of careful monitoring in patients on warfarin who require concurrent antibiotic medication, as this approach is crucial in reducing the risk of significant bleeding problems. Moreover, for patients requiring cytochrome P450 inhibitors such penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides, contemplating a dose reduction in warfarin medication may significantly diminish the risk of serious bleeding incidents. Patients receiving rifampin along with warfarin require careful monitoring, potentially necessitating increased warfarin dosages to mitigate the danger of a hypercoagulable state.