What to do for a patient with an elevated International Normalized Ratio (INR) on Xarelto (rivaroxaban)?

Management of INR 6.7 on Rivaroxaban (Xarelto)

For a patient with an INR of 6.7 while on rivaroxaban, discontinue the medication immediately and consider activated charcoal if the last dose was taken within the past few hours. 1

Understanding the Situation

• Rivaroxaban (Xarelto) is a direct factor Xa inhibitor that does not typically require INR monitoring, as INR is not a reliable measurement for rivaroxaban activity 2
• An INR of 6.7 while on rivaroxaban indicates a potentially dangerous supratherapeutic level that significantly increases bleeding risk 3
• This abnormally high INR could be due to drug interactions, declining renal function, or other factors affecting rivaroxaban metabolism 4

Immediate Management Steps

1. Discontinue rivaroxaban immediately to prevent further elevation of anticoagulant effect 1
2. Assess for bleeding at all potential sites (gastrointestinal, genitourinary, intracranial, etc.) as the risk of major bleeding rises steeply with INR >6.0 5
3. Consider activated charcoal if the last dose was taken within the past few hours to reduce absorption 1
4. Obtain laboratory tests including complete blood count, renal function, and liver function tests 5

Management Based on Bleeding Status

If No Active Bleeding:

• Monitor the patient closely with serial INR measurements and observation for signs of bleeding 5
• Allow the INR to fall gradually without immediate reversal agents if the patient is stable 5
• Investigate potential causes of elevated INR:
  • Drug interactions (particularly CYP3A4 and P-glycoprotein inhibitors like amiodarone) 4
  • Declining renal function (rivaroxaban is partially renally cleared) 4
  • Hepatic impairment 1

If Active Bleeding:

• Provide hemodynamic support and local measures to control bleeding 5
• Consider administration of prothrombin complex concentrate or specific factor Xa reversal agent (andexanet alfa) if available, especially if bleeding is life-threatening 1
• Fresh frozen plasma may be considered if specific reversal agents are unavailable 5
• For intracranial hemorrhage, immediate reversal of anticoagulation is necessary 5

Monitoring and Follow-up

• Repeat INR measurement within 24 hours to ensure declining trend 5
• Monitor for signs of thromboembolism during the period off anticoagulation 5
• Consider measuring direct rivaroxaban levels if available, as INR is not a reliable indicator of rivaroxaban activity 6

Restarting Anticoagulation

• The decision to restart anticoagulation should be based on:
  • Resolution of bleeding risk
  • Original indication for anticoagulation
  • Patient's risk factors for thromboembolism 5
• For patients with high thrombotic risk (mechanical heart valves, recent thromboembolism), consider bridging with heparin once bleeding risk has resolved 5
• Consider lower dose of rivaroxaban or alternative anticoagulant when restarting therapy 1

Common Pitfalls and Caveats

• Do not rely on INR to monitor rivaroxaban therapy - INR is designed for vitamin K antagonists and is not reliable for direct oral anticoagulants 2
• Point-of-care INR testing devices may be particularly inaccurate with rivaroxaban and can show falsely elevated readings 2
• Rivaroxaban is not dialyzable due to high plasma protein binding, limiting options for rapid clearance 1
• Elderly patients and those with renal impairment are at particularly high risk for supratherapeutic rivaroxaban levels and should be monitored more closely 4