Can You Take Levetiracetam (Keppra) with Ibuprofen?
Yes, you can safely take levetiracetam with ibuprofen—there are no known drug interactions between these medications, and research actually suggests they may work synergistically for pain relief.
Safety Profile of the Combination
No contraindications exist for concurrent use of levetiracetam and ibuprofen based on current clinical guidelines and pharmacological evidence 1.
Levetiracetam is commonly used in various clinical settings (seizure management, CAR T-cell therapy prophylaxis) without restrictions on concurrent NSAID use 1, 2, 3.
The 2024 VA/DoD headache management guidelines recommend ibuprofen for migraine treatment without any warnings about levetiracetam interactions, despite levetiracetam being discussed in the same guideline for migraine prevention 1.
Evidence of Synergistic Benefit
Preclinical research demonstrates synergistic antinociceptive effects when levetiracetam is combined with ibuprofen, showing a 15-fold dose reduction of both drugs when used together in a diabetic neuropathy pain model 4.
This synergism suggests the combination may provide enhanced pain relief with potentially lower doses of each medication, though this has only been studied in animal models 4.
Clinical Context Where Both Are Used
Seizure management: Patients on levetiracetam for epilepsy can safely use ibuprofen for pain, fever, or inflammation 1, 5.
Post-procedural settings: Patients receiving levetiracetam prophylaxis (such as after CAR T-cell therapy at 10 mg/kg every 12 hours) can take ibuprofen for concurrent pain management 1, 2.
Headache treatment: Ibuprofen 400 mg is recommended for tension-type headache and migraine, with no restrictions for patients on levetiracetam 1.
Important Caveats
While the combination is safe from a drug interaction standpoint, monitor for levetiracetam's behavioral side effects (irritability 67%, hyperactivity 8%, somnolence 6%) which are the most common adverse events 5.
Standard NSAID precautions apply: Consider gastrointestinal protection in high-risk patients, monitor renal function with chronic use, and avoid in patients with contraindications to NSAIDs 1.
If using levetiracetam for acute seizure management with loading doses (40-60 mg/kg IV), ibuprofen can still be administered concurrently without dose adjustments 2, 3, 6.