From the Research
Community-acquired pneumonia (CAP) antibiotics that can significantly affect International Normalized Ratio (INR) levels include azithromycin, clarithromycin, levofloxacin, moxifloxacin, and trimethoprim-sulfamethoxazole, with macrolides and fluoroquinolones being the most notable interactions. These antibiotics can increase INR values by inhibiting cytochrome P450 enzymes that metabolize warfarin, displacing warfarin from protein binding sites, or reducing vitamin K-producing gut flora 1.
Key Interactions
- Macrolides (especially clarithromycin) and fluoroquinolones (particularly levofloxacin and moxifloxacin) can increase bleeding risk by elevating INR levels
- Trimethoprim-sulfamethoxazole often causes the most pronounced effect on INR levels
- Doxycycline and amoxicillin generally have minimal effects on INR and may be preferred options when appropriate for the clinical situation
Clinical Implications
- Patients on warfarin who require these antibiotics for CAP should have more frequent INR monitoring, typically within 3-5 days of starting the antibiotic therapy
- Dose adjustments of warfarin may be necessary during and after antibiotic treatment
- Clinicians should always consider these interactions when selecting CAP treatment for patients on anticoagulation therapy, as noted in studies such as 2 and 3.
Preferred Options
- Doxycycline and amoxicillin may be preferred options for CAP treatment in patients on anticoagulation therapy due to their minimal effects on INR levels
- Azithromycin containing regimens were associated with the lowest rates of nonresponsiveness in a study on CAP treatment 2