Which of the following drugs significantly increases the INR when used with Warfarin?

• A. Levofloxacin
• B. Fluconazole
• C. Erythromycin
• D. Amiodarone

Answer: (A)

The drug that significantly increases the INR when used with Warfarin is amiodarone. This medication is a class III antiarrhythmic that can interact with Warfarin by inhibiting the hepatic metabolism of Warfarin, primarily through the CYP450 enzyme system. This inhibition can lead to elevated INR levels, meaning that the anticoagulant effect of Warfarin is enhanced, which raises the risk of bleeding.

It is essential for patients on Warfarin to have their INR closely monitored when starting or stopping amiodarone, as even small changes in Warfarin's metabolism can lead to significant differences in its anticoagulant effect. This interaction is well-documented, and clinicians often adjust Warfarin doses when amiodarone is introduced to maintain therapeutic INR levels.

The other options listed do have potential interactions with Warfarin, but they do not usually cause as significant an increase in INR as amiodarone does. For instance, fluconazole (an antifungal) can increase the INR but to a lesser extent compared to amiodarone. Erythromycin (an antibiotic) can also increase INR, but its interaction is typically not as pronounced. Levofloxacin, while it may have