Does Augmentin (amoxicillin/clavulanate) affect International Normalized Ratio (INR) levels?

Augmentin Can Affect INR Levels in Patients on Warfarin

Augmentin (amoxicillin/clavulanate) can increase INR levels in patients taking warfarin, requiring closer monitoring and potential warfarin dose adjustments to prevent bleeding complications. 1

Mechanism of Interaction

The interaction between Augmentin and warfarin occurs through several potential mechanisms:

1. Alteration of gut flora: The primary mechanism involves Augmentin reducing vitamin K-producing intestinal bacteria, leading to vitamin K deficiency and enhanced warfarin effect 1, 2

2. Potential protein binding displacement: Though less established, Augmentin may compete with warfarin for protein binding sites

Clinical Significance

This interaction is explicitly mentioned in the FDA drug label for amoxicillin/clavulanate, which states: "Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants." 1

Monitoring and Management

When prescribing Augmentin to patients on warfarin:

1. Increase INR monitoring frequency:

   • Check INR within 3-7 days of starting Augmentin
   • Continue monitoring until 1 week after completing the antibiotic course
   • More frequent monitoring may be needed for high-risk patients (elderly, history of bleeding)

2. Adjust warfarin dosing as needed:

   • Be prepared to reduce warfarin dose if INR rises above therapeutic range
   • The FDA label specifically states: "Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation" 1

3. Watch for bleeding signs:

   • Educate patients about signs of bleeding (bruising, blood in urine, black stools)
   • Instruct patients to seek immediate medical attention if bleeding occurs

Risk Factors for Enhanced Interaction

Certain patients may be more susceptible to this interaction:

• Elderly patients
• Those with vitamin K deficiency (12% of anticoagulated patients may have very low vitamin K levels) 3
• Patients with renal or hepatic impairment
• Patients taking multiple medications that affect warfarin metabolism

Common Pitfalls to Avoid

1. Failure to monitor: Studies show that INR monitoring within 14 days of antibiotic initiation occurs in only 77% of cases, with monitoring for penicillins occurring in only 71% of cases 4

2. Attributing INR changes solely to antibiotics: Remember that bleeding events themselves can increase INR values, creating a potentially dangerous cycle 5

3. Overlooking other concurrent medications: NSAIDs and other medications that affect bleeding risk or warfarin metabolism can compound the risk 6

4. Ignoring patient-specific factors: Low vitamin K status may make patients more sensitive to even small changes in vitamin K intake or absorption 3

This interaction is clinically significant and requires proactive management to prevent adverse outcomes related to either excessive anticoagulation (bleeding) or insufficient anticoagulation (thrombosis).