Is Augmentin (amoxicillin-clavulanate) safe to use with Warfarin?

From the Guidelines

Augmentin can be used with warfarin, but close monitoring of INR is recommended due to the potential increased risk of bleeding. According to a recent study published in Circulation: Arrhythmia and Electrophysiology in 2022 1, all antibiotics, including Augmentin, can alter the gut microbiome, which is a rich source of vitamin K, and thereby potentiate anticoagulant effects of warfarin. This interaction can lead to an increased risk of bleeding, and patients taking both medications should be closely monitored.

Key Considerations

• Patients taking Augmentin and warfarin should have their INR monitored more frequently, especially when starting or stopping Augmentin.
• The antibiotic component of Augmentin can potentially alter the gut flora that metabolize vitamin K, which may enhance warfarin's anticoagulant effect.
• Patients should watch for signs of increased bleeding such as unusual bruising, nosebleeds, blood in urine or stool, or prolonged bleeding from cuts.
• It's essential to inform all healthcare providers about all medications being taken, including over-the-counter drugs and supplements.
• If bleeding occurs or if INR values increase significantly, medical attention should be sought immediately.

Management

• A prospective study of 120 patients who received a combination of amoxicillin/clavulanate, found that patients who received the higher maintenance dose (10–12 g/day) versus the usual dose (3.6 g/day) developed a higher proportion of INR values ≥ 4 1.
• Pre-emptive warfarin dose reductions may be necessary when co-administered with certain antibiotics, but the specific reduction for Augmentin is not well established.
• Despite these precautions, when properly monitored, many patients can safely take both medications together.

From the Research

Interaction between Augmentin and Warfarin

• The interaction between Augmentin (amoxicillin/clavulanate) and warfarin is a significant concern, as it can lead to increased anticoagulation and bleeding risk 2, 3, 4.
• Studies have shown that the concomitant use of Augmentin and warfarin can result in elevated international normalized ratio (INR) levels, increasing the risk of bleeding complications 2, 3, 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.
• A systematic review and meta-analysis found that the use of antimicrobials, including Augmentin, with warfarin increases the risk of clinically relevant bleeding 6.
• Case reports have highlighted the potential for serious bleeding complications, including rectus sheath hematoma, when Augmentin is used in patients taking warfarin 4.
• It is essential to monitor INR levels closely when Augmentin is prescribed to patients taking warfarin, and to adjust the warfarin dose as needed to minimize the risk of bleeding complications 2, 3, 5.

Clinical Implications

• Healthcare providers should be aware of the potential interaction between Augmentin and warfarin and take steps to minimize the risk of bleeding complications 2, 3, 5.
• Patients taking warfarin should be closely monitored for signs of bleeding, and their INR levels should be checked regularly when Augmentin is prescribed 2, 3, 5.
• Alternative antibiotics may be considered in patients taking warfarin, especially if they have a history of bleeding complications or are at high risk of bleeding 6.