Safety of Taking Keppra (Levetiracetam) While on Warfarin
Levetiracetam (Keppra) can be safely taken with warfarin as it does not interact with warfarin's metabolism or affect prothrombin time. 1
Evidence on Levetiracetam-Warfarin Interaction
The FDA drug label for levetiracetam specifically addresses this interaction:
- Clinical studies have shown that levetiracetam (1000 mg twice daily) does not influence the pharmacokinetics of R and S warfarin 1
- Prothrombin time is not affected by levetiracetam 1
- Coadministration of warfarin does not affect the pharmacokinetics of levetiracetam 1
Unlike many other medications, levetiracetam has several pharmacological properties that make it a safer choice when combined with warfarin:
- Levetiracetam circulates largely unbound (<10% bound) to plasma proteins, making clinically significant interactions through protein binding competition unlikely 1
- It is not extensively metabolized in humans and is not dependent on liver cytochrome P450 enzymes 1
- The major metabolic pathway is enzymatic hydrolysis of the acetamide group, which is independent of liver cytochrome P450 isoenzymes 1
Recent Research Confirmation
A 2023 study specifically investigating anticoagulant therapy with levetiracetam found no evidence of reduced anticoagulant effect or increased thromboembolic risk when these medications were used together 2. Although this study focused on direct oral anticoagulants rather than warfarin specifically, it supports the overall safety profile of levetiracetam with anticoagulants.
Contrasting with High-Risk Drug Combinations
This safety profile contrasts sharply with many other medications that do interact dangerously with warfarin:
- CYP2C9 inhibitors significantly increase bleeding risk (OR 3.6) 3
- NSAIDs and COX-2 inhibitors substantially increase bleeding risk (OR 2.6 and 3.1 respectively) 3, 4
- Selective serotonin reuptake inhibitors (SSRIs) are associated with higher bleeding risk (OR 2.6) 3
Monitoring Considerations
While levetiracetam itself doesn't interact with warfarin, it's still important to maintain regular INR monitoring when starting any new medication, as standard practice for patients on warfarin therapy. This is particularly important because:
- Approximately 80% of atrial fibrillation patients on warfarin are prescribed at least one warfarin-potentiating medication 5
- The risk of major bleeding begins to rise significantly when INR exceeds 4.5 6
Conclusion
Based on the FDA drug label and supporting research, levetiracetam (Keppra) can be safely taken with warfarin without special dosage adjustments or additional monitoring beyond standard care. This makes it one of the safer antiepileptic options for patients requiring concurrent anticoagulation therapy.