From the Guidelines
Amoxicillin-clavulanate can be used with warfarin, but it requires careful monitoring due to potential interactions, as evidenced by 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. When taking these medications together, there is an increased risk of bleeding because amoxicillin-clavulanate may enhance warfarin's anticoagulant effect. This interaction occurs because the antibiotic can disrupt intestinal flora that produce vitamin K (which helps blood clot) and may interfere with warfarin metabolism in the liver. Some key points to consider when using amoxicillin-clavulanate with warfarin include:
- Monitoring INR more frequently during and shortly after antibiotic treatment
- Watching for signs of increased bleeding such as unusual bruising, nosebleeds, bleeding gums, or blood in urine or stool
- Contacting healthcare provider immediately if signs of bleeding occur
- Not adjusting warfarin dose without medical guidance
- Informing all healthcare providers about all medications being taken to prevent potential drug interactions. It is crucial to follow the healthcare provider's guidance and monitoring recommendations to minimize the risk of adverse effects when taking amoxicillin-clavulanate with warfarin, as supported by the study published in Circulation: Arrhythmia and Electrophysiology 1.
From the Research
Interaction between Amoxicillin Clavulanate and Warfarin
- The interaction between amoxicillin clavulanate and warfarin can lead to increased international normalized ratio (INR) values and bleeding risk 2, 3, 4.
- A case study reported a 53-year-old male with a history of protein C deficiency and recurrent intravascular thrombosis who developed significant bleeding after tooth extraction while taking amoxicillin/clavulanate and warfarin, with an INR of 20.4 2.
- A prospective cross-sectional observational study found that high-dose amoxicillin/clavulanate (10-12 g daily) was associated with a higher risk of over-anticoagulation when combined with warfarin than normal doses (up to 3.6 g daily) 3.
- Another study reported a case of warfarin-amoxicillin/clavulanate interaction resulting in an elevated INR and hematuria, suggesting that the mechanism of interaction may be related to a decrease in vitamin K-producing gut flora 4.
Clinical Implications
- The interaction between amoxicillin clavulanate and warfarin can be clinically significant, and prompt recognition and intervention are necessary to avoid life-threatening complications 2, 3, 4.
- Frequent monitoring of warfarin therapy and INR values is recommended when amoxicillin/clavulanate is concomitantly administered 3.
- However, a randomized controlled trial found that amoxicillin/clavulanic acid did not modify anticoagulation in patients treated with stable warfarin therapy and without infection 5.
Comparison with Other Antibiotics
- The effect of azithromycin on anticoagulation-related outcomes in geriatric patients receiving warfarin was studied, and the results showed a significant change in INR values and warfarin dosage alteration without an increase in bleeding 6.
- In contrast, the interaction between amoxicillin clavulanate and warfarin appears to be more significant, with a higher risk of over-anticoagulation and bleeding 2, 3, 4.