When should the International Normalized Ratio (INR) be checked in patients taking Coumadin (warfarin) who are initiated on Augmentin (amoxicillin-clavulanate)?

INR Monitoring When Starting Augmentin While on Coumadin

When a patient on Coumadin (warfarin) is started on Augmentin (amoxicillin-clavulanate), the INR should be checked within 3-7 days after initiating the antibiotic to monitor for potential interactions that may increase the anticoagulant effect. 1

Rationale for INR Monitoring with Augmentin and Warfarin

Augmentin can interact with warfarin in several ways:

1. Direct drug interaction: The FDA drug label for Augmentin specifically states that "abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants" and recommends that "appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with amoxicillin and clavulanate potassium." 1

2. Antibiotic effect on gut flora: All antibiotics can alter the gut microbiome, which is a rich source of vitamin K, potentially enhancing warfarin's anticoagulant effects. 2

Monitoring Protocol

Timing of INR Testing

• First INR check: 3-7 days after starting Augmentin
• Follow-up monitoring: Based on initial results and clinical judgment

Risk Stratification

Patients at higher risk for INR elevation include:

• Elderly patients (≥65 years)
• Those with history of stroke or GI bleeding
• Patients with renal insufficiency or anemia
• Patients with multiple risk factors 2

Management Algorithm

1. Before starting Augmentin:

   • Document baseline INR (ideally within therapeutic range)
   • Consider patient's bleeding risk factors

2. During Augmentin therapy:

   • Monitor INR within 3-7 days of starting the antibiotic
   • Continue regular monitoring until INR stabilizes after completing the antibiotic course

3. If INR becomes elevated:

   • For INR >5 but <9 without bleeding: Consider omitting 1-2 doses of warfarin and reinstate at a lower dose when INR returns to therapeutic range 2
   • For INR ≥9 without bleeding: Consider oral vitamin K₁ (3-5 mg) 2
   • For any significant bleeding: More aggressive management with vitamin K₁ and possible fresh plasma 2

Evidence on Clinical Impact

Research shows that antibiotics can increase the risk of excessive anticoagulation. A retrospective study found that 3.2% of patients on warfarin who received antibiotics experienced an INR ≥5.0, compared to only 1.2% in stable control patients. 3

A case report specifically documented a patient on stable warfarin therapy who developed a rectus sheath hematoma after taking amoxicillin-clavulanate, with INR rising to 5.7 from a previously stable therapeutic range. 4

Important Considerations

• Preemptive dose reduction: Some evidence suggests that preemptive warfarin dose reduction (25% for certain antibiotics) upon antibiotic initiation may help maintain therapeutic INR and reduce the need for follow-up visits. 5

• Outpatient follow-up: For patients discharged from the hospital on both warfarin and Augmentin, INR follow-up should be scheduled within 2 weeks for patients newly prescribed warfarin or within 30 days for patients previously on warfarin. 2

• Duration of monitoring: Continue close monitoring for at least 1 week after completing the antibiotic course, as effects on INR may persist beyond the treatment period.

Common Pitfalls to Avoid

1. Assuming all patients will have significant INR elevation: While interaction is possible, a study of dental patients found only 2.7% had INR values increase beyond therapeutic range after prophylactic antibiotics. 6

2. Neglecting follow-up: Failure to schedule and complete timely INR monitoring after starting Augmentin can lead to undetected supratherapeutic anticoagulation.

3. Overlooking other factors: Acute illness itself (such as infection requiring antibiotics) can independently increase INR values, regardless of antibiotic use. 3