Does Augmentin (amoxicillin-clavulanate) affect warfarin levels?

From the Guidelines

Augmentin can significantly affect warfarin levels, potentially increasing the risk of bleeding, and patients taking both medications should have their INR monitored closely. When Augmentin is taken with warfarin, it can elevate the INR and enhance warfarin's anticoagulant effect, as all antibiotics can alter the gut microbiome, which is a rich source of vitamin K, and thereby potentiate anticoagulant effects of warfarin 1. The interaction between Augmentin and warfarin has been reported in a prospective study of 120 patients who received a combination of amoxicillin/clavulanate, where patients who received the higher maintenance dose developed a higher proportion of INR values ≥ 4 1.

Key Considerations

• The mechanism involves Augmentin disrupting vitamin K-producing intestinal bacteria and potentially inhibiting warfarin metabolism in the liver.
• Patients taking both medications should have their INR monitored more frequently, especially within the first week of starting Augmentin and after completing the course.
• Any signs of unusual bleeding, such as nosebleeds, bleeding gums, or blood in urine or stool, should prompt immediate medical attention.
• Healthcare providers may need to adjust the warfarin dose temporarily while the patient is on Augmentin, with pre-emptive warfarin dose reductions recommended when co-administered with certain antibiotics 1.

Monitoring and Management

• It's essential to inform all healthcare providers about all medications being taken to prevent potentially dangerous drug interactions.
• Close monitoring of INR levels and adjustment of warfarin doses as needed can help minimize the risk of bleeding complications.
• The antibiotic dose will also contribute to the severity of this interaction, and higher maintenance doses may require more significant adjustments to warfarin doses 1.

From the FDA Drug Label

There have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium and anticoagulant therapy concomitantly. [see DRUG INTERACTIONS (7. 2)]

Augmentin (amoxicillin-clavulanate) may affect warfarin levels by increasing prothrombin time in patients receiving both medications concomitantly 2.

From the Research

Augmentin and Warfarin Interaction

• Augmentin, also known as amoxicillin/clavulanate, can interact with warfarin, affecting its levels and increasing the risk of bleeding complications 3, 4, 5.
• The mechanism of this interaction is suspected to be related to the decrease in vitamin K-producing gut flora, resulting in vitamin K deficiency 3.
• Studies have reported cases of elevated international normalized ratio (INR) and bleeding episodes in patients taking warfarin and amoxicillin/clavulanate concurrently 3, 4, 5.
• A retrospective cohort study found that antibiotic coadministration, including amoxicillin/clavulanate, increased the risk of excessive anticoagulation in patients with stable warfarin therapy 6.
• The risk of excessive anticoagulation was higher in patients taking antibiotics that interfere with warfarin metabolism, such as amoxicillin/clavulanate 6.

Clinical Implications

• Patients taking warfarin and amoxicillin/clavulanate concurrently should be closely monitored for signs of bleeding and INR levels 3, 4, 5.
• Healthcare providers should be aware of the potential interaction between warfarin and amoxicillin/clavulanate and take necessary precautions to prevent bleeding complications 3, 4, 5.
• The use of amoxicillin/clavulanate in patients taking warfarin should be carefully considered, and alternative antibiotics should be used if possible 6.