What anti-inflammatory is safe to use with Keppra (levetiracetam) and Zonisamide?

Safe Anti-inflammatory Options with Keppra (Levetiracetam) and Zonisamide

Naproxen is the safest anti-inflammatory medication to use with Keppra (levetiracetam) and zonisamide due to its favorable cardiovascular profile and lack of significant interactions with these antiepileptic drugs. 1

Compatibility of NSAIDs with Antiepileptic Medications

According to clinical guidelines, both levetiracetam and zonisamide are classified as "weight neutral/less weight gain" anti-epileptic medications that don't have significant documented interactions with standard NSAIDs 2. This makes them generally compatible with anti-inflammatory medications when necessary.

Key considerations when selecting an NSAID:

1. Cardiovascular safety profile:

   • Naproxen has the most favorable cardiovascular safety profile among NSAIDs with a relative risk of vascular events of 0.92 compared to placebo 1
   • Diclofenac (RR 1.63) and ibuprofen (RR 1.51) have significantly higher cardiovascular risks compared to naproxen 1

2. Gastrointestinal risk assessment:

   • For patients under 65 with no previous GI events and not on aspirin, a standard NSAID alone is appropriate 2
   • For patients with previous GI events or on aspirin, an NSAID with a proton pump inhibitor (PPI) is recommended 2

Algorithm for NSAID Selection with Keppra and Zonisamide

Step 1: Assess baseline risk factors

• Age (over/under 65)
• History of GI events (ulcers, bleeding)
• Concurrent aspirin use
• Cardiovascular risk factors

Step 2: Select appropriate NSAID based on risk profile

• Low risk (under 65, no GI history, no aspirin, low CV risk):

  • Naproxen (preferred) at standard dosing
  • Alternative: Ibuprofen (but higher CV risk than naproxen)

• Moderate risk (over 65 OR GI history OR aspirin use):

  • Naproxen + PPI (e.g., omeprazole 20mg daily)

• High risk (multiple risk factors OR previous complicated GI event):

  • Naproxen + PPI at lowest effective dose
  • Consider acetaminophen as alternative if pain is mild to moderate

Step 3: Monitoring recommendations

• Monitor for seizure control
• Check blood pressure within 1-2 weeks of starting NSAID therapy
• Assess baseline renal function before starting NSAIDs

Important Precautions

1. Avoid combination NSAID therapy - Do not combine multiple NSAIDs or NSAIDs with aspirin unless specifically directed 2

2. Limit duration and dosage - Use the lowest effective dose for the shortest duration possible 2

3. Monitor renal function - Baseline assessment of renal function is recommended before starting NSAIDs, especially important with antiepileptic medications 1

4. Consider alternative pain management for patients with high-risk profiles:

   • Acetaminophen (limit to 3g/day)
   • Topical NSAIDs
   • Non-pharmacological approaches (physical therapy, heat/cold therapy)

Conclusion

For most patients on levetiracetam (Keppra) and zonisamide, naproxen is the safest NSAID option due to its favorable cardiovascular profile and compatibility with these antiepileptic medications. For patients with GI risk factors, adding a PPI provides additional protection. Always use the lowest effective dose for the shortest duration needed to manage symptoms.