What effect do macrolides have on warfarin therapy that could increase bleeding risk?

• A. They reduce warfarin's effect
• B. They inhibit hepatic metabolism of warfarin, increasing INR
• C. They induce hepatic metabolism of warfarin
• D. They have no interaction

Answer: (B)

Macrolides can slow the liver’s breakdown of warfarin by inhibiting the cytochrome P450 enzymes that metabolize it. When metabolism is inhibited, warfarin levels stay higher in the blood, increasing its anticoagulant effect and raising the INR. A higher INR means a greater risk of bleeding. This interaction is most notable with erythromycin and clarithromycin; azithromycin has a weaker effect but can still interact. In practice, starting a macrolide with warfarin calls for closer INR monitoring and possible warfarin dose adjustment or choosing an alternative antibiotic if feasible.