How can macrolide antibiotics interact with warfarin?

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

Answer: (B)

Macrolide antibiotics can raise the effects of warfarin by slowing its breakdown in the liver. Warfarin is metabolized by hepatic enzymes, and when these enzymes are inhibited by a macrolide, warfarin remains in the bloodstream longer. This increases the anticoagulant effect, raising the INR and the risk of bleeding. Erythromycin and clarithromycin are classic examples of macrolides with this interaction; azithromycin can cause it too, though to a lesser extent. In practice, starting a macrolide with warfarin means INR should be monitored more closely and the warfarin dose may need adjustment, or an alternative antibiotic should be considered. Remember that antibiotics can also affect vitamin K-producing gut bacteria, which can further influence anticoagulation, but the key mechanism is reduced warfarin metabolism leading to higher levels.