Does Augmentin (amoxicillin/clavulanate) affect International Normalized Ratio (INR) levels in patients taking warfarin?

From the Guidelines

Augmentin (amoxicillin/clavulanate) can increase INR levels in patients taking warfarin, and close monitoring of INR is recommended, especially in patients receiving higher maintenance doses of Augmentin. This is because all antibiotics, including Augmentin, can alter the gut microbiome, which is a rich source of vitamin K, thereby potentiating the anticoagulant effects of warfarin 1. 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.

When prescribing Augmentin to patients on warfarin therapy, more frequent INR monitoring is recommended, particularly during the first week of antibiotic treatment and shortly after discontinuation. The interaction appears to be more significant in elderly patients, those with poor nutritional status, or patients with other medical conditions affecting vitamin K metabolism. Patients taking both medications should be vigilant for signs of increased bleeding such as unusual bruising, nosebleeds, blood in urine or stool, or excessive bleeding from minor cuts. If these occur, medical attention should be sought immediately. Healthcare providers may need to temporarily adjust warfarin dosing during Augmentin treatment based on INR results.

Some key points to consider when managing patients on warfarin and Augmentin include:

• Close monitoring of INR levels, especially in the first week of treatment and after discontinuation of Augmentin
• Being aware of the potential for increased bleeding risk, particularly in vulnerable patient populations
• Considering temporary adjustments to warfarin dosing based on INR results
• Educating patients on the signs of increased bleeding and the importance of seeking medical attention if these occur.

From the FDA Drug Label

7.2 Oral Anticoagulants Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with amoxicillin and clavulanate potassium Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Yes, Augmentin (amoxicillin/clavulanate) can affect INR levels in patients taking warfarin. According to the drug label, abnormal prolongation of prothrombin time (increased INR) has been reported in patients receiving amoxicillin and oral anticoagulants, such as warfarin. Therefore, appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with Augmentin, and adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation 2.

From the Research

Augmentin and INR Interaction

• Augmentin, a combination of amoxicillin and clavulanate, is known to interact with warfarin, affecting International Normalized Ratio (INR) levels in patients taking warfarin 3.
• A case report published in The Annals of Pharmacotherapy in 2003 described a patient who developed an elevated INR and hematuria as a result of a drug-drug interaction between warfarin and amoxicillin/clavulanate potassium (Augmentin) 3.
• The mechanism of this interaction is suspected to be a decrease in vitamin K-producing gut flora, resulting in vitamin K deficiency 3.
• Another study published in Pharmacotherapy in 2005 found that monitoring of INR values occurred more frequently when warfarin was coprescribed with certain antimicrobial agents, including fluoroquinolones, metronidazole, tetracyclines, and macrolides, compared to penicillins, which includes Augmentin 4.
• However, the study did not specifically investigate the effect of Augmentin on INR levels in patients taking warfarin.

Clinical Implications

• The interaction between Augmentin and warfarin can lead to elevated INR levels, increasing the risk of bleeding complications 3.
• Clinicians should be aware of this potential interaction and monitor INR levels closely in patients taking warfarin and Augmentin concurrently 3.
• Patients should also be educated about the potential risks of taking Augmentin while on warfarin therapy and the importance of regular INR monitoring 3.

Comparison with Other Interactions

• Other studies have investigated the interactions between warfarin and other medications, such as acetaminophen 5, 6 and telithromycin 7.
• These studies have found that certain medications can increase the risk of elevated INR levels and bleeding complications in patients taking warfarin.
• However, the specific interaction between Augmentin and warfarin is less well-studied, and further research is needed to fully understand the clinical implications of this interaction.