Is there a drug interaction between oseltamivir (Tamiflu) and levetiracetam (Keppra)?

Drug Interaction Between Oseltamivir and Levetiracetam

There is no clinically significant drug interaction between oseltamivir (Tamiflu) and levetiracetam (Keppra). Both medications can be safely administered together without dose adjustments.

Mechanism of Action and Elimination Pathways

Oseltamivir

• Oseltamivir is a prodrug that is converted to its active metabolite, oseltamivir carboxylate
• Eliminated primarily through renal excretion via:
  • Glomerular filtration
  • Tubular secretion via the anionic pathway 1

Levetiracetam

• Primarily eliminated unchanged through the kidneys
• Does not undergo significant hepatic metabolism
• Not known to interact with the anionic renal secretion pathway used by oseltamivir

Evidence for Lack of Interaction

The available guidelines and research do not document any interaction between oseltamivir and levetiracetam. The CDC guidelines specifically state that limited clinical data are available regarding drug interactions with oseltamivir, with the only documented significant interaction being with probenecid 1.

When oseltamivir is co-administered with probenecid, there is:

• Reduced clearance of oseltamivir carboxylate by approximately 50%
• Corresponding twofold increase in plasma levels of oseltamivir carboxylate 1

This interaction occurs because probenecid inhibits the renal anionic secretion pathway. Levetiracetam does not affect this pathway and therefore would not be expected to interact with oseltamivir in this manner.

Known Drug Interactions with Oseltamivir

The only clinically significant drug interaction with oseltamivir that is consistently documented in guidelines is with probenecid 1. No other significant interactions have been reported in clinical practice or research.

In vitro and in vivo studies indicate that oseltamivir:

• Does not interact with cytochrome P450 mixed-function oxidases
• Does not interact with glucuronosyltransferases 2
• Has low potential for drug-drug interactions at the renal tubular level 3

Monitoring Considerations

While no specific interaction exists between these medications, standard monitoring is recommended when administering either drug:

For oseltamivir:

• Monitor for common side effects such as nausea and vomiting (occurs in approximately 10% of adults) 1
• Be alert for rare neuropsychiatric events, especially in pediatric patients 1

For levetiracetam:

• Continue standard monitoring for seizure control
• Watch for common side effects including somnolence, dizziness, and behavioral changes

Conclusion

Based on the available evidence, oseltamivir and levetiracetam can be safely administered concurrently without dose adjustments or special monitoring beyond what is standard for each medication individually. Their different elimination pathways and mechanisms of action do not create conditions for a clinically significant drug interaction.