Interactions Between Keppra (Levetiracetam) and NSAIDs
No clinically significant pharmacokinetic interactions exist between Keppra (levetiracetam) and NSAIDs, making them generally safe to use together.
Pharmacokinetic Profile of Levetiracetam
Levetiracetam has several pharmacokinetic properties that contribute to its low interaction potential:
Minimal hepatic metabolism: Unlike many other antiepileptic drugs, levetiracetam is not extensively metabolized by the liver. Approximately 66% is excreted unchanged in urine, with only 34% undergoing metabolism 1.
No cytochrome P450 involvement: Levetiracetam does not induce or inhibit cytochrome P450 enzymes, which significantly reduces its potential for drug interactions 2.
Limited protein binding: Levetiracetam is not bound to plasma proteins, eliminating the risk of displacement interactions that are common with many NSAIDs 1, 2.
Unique elimination pathway: The metabolism of levetiracetam occurs primarily through hydrolysis in the blood rather than through hepatic pathways 1.
NSAIDs and Their Interaction Potential
NSAIDs can interact with many medications through several mechanisms:
- Protein displacement
- Inhibition of renal excretion
- Alteration of metabolism
- Pharmacodynamic interactions
However, these mechanisms do not significantly affect levetiracetam due to its unique pharmacokinetic profile.
Clinical Evidence and Guidelines
The National Comprehensive Cancer Network guidelines specifically mention levetiracetam as a preferred non-enzyme-inducing antiepileptic drug (non-EIAED) that should be used instead of enzyme-inducing AEDs like phenytoin, phenobarbital, and carbamazepine 3. This recommendation is particularly relevant when considering potential drug interactions.
In pediatric patients receiving chimeric antigen receptor T cell therapy, levetiracetam is recommended as the anti-seizure prophylaxis of choice (10 mg/kg, up to 500 mg per dose every 12 hours) due to its minimal risk of adverse drug interactions 3.
Special Considerations
While there are no significant pharmacokinetic interactions between levetiracetam and NSAIDs, there are some clinical considerations to keep in mind:
Renal function: Both levetiracetam and NSAIDs are eliminated through the kidneys. In patients with renal impairment, dose adjustments of levetiracetam may be necessary 1. NSAIDs can also affect renal function, potentially requiring monitoring in patients on both medications.
Elderly patients: Elderly patients may be more susceptible to adverse effects from both medications and may require closer monitoring.
Patients with cardiovascular risk: NSAIDs can increase blood pressure and cardiovascular risk, which should be considered in patients with pre-existing conditions 4.
Monitoring Recommendations
When using levetiracetam and NSAIDs together:
- Monitor renal function, particularly in elderly patients or those with pre-existing renal impairment
- Be aware of potential NSAID side effects (gastrointestinal, cardiovascular, renal)
- No specific additional monitoring is required for the combination beyond what would be standard for each medication individually
Conclusion
The combination of levetiracetam and NSAIDs is generally considered safe from a pharmacokinetic perspective. Levetiracetam's favorable pharmacokinetic profile, including minimal protein binding, lack of cytochrome P450 involvement, and unique metabolism pathway, makes it unlikely to interact significantly with NSAIDs.