Does levetiracetam (Keppra) decrease the serum concentration of brivaracetam (Briviact), and if so, what alternative antiepileptic medications can be considered?

Does Levetiracetam Decrease Serum Concentration of Brivaracetam?

No, levetiracetam does not decrease the serum concentration of brivaracetam. In fact, the opposite occurs: levetiracetam may slightly increase brivaracetam plasma concentrations, though this effect is not clinically significant and requires no dose adjustment 1.

Pharmacokinetic Interaction Profile

Brivaracetam has minimal drug-drug interactions and does not require dose adjustment when co-administered with levetiracetam 1. The favorable pharmacokinetic profile of brivaracetam allows administration without dose modification when combined with most commonly prescribed antiepileptic drugs 1.

Agents That Actually Decrease Brivaracetam Levels

The only medications that meaningfully reduce brivaracetam plasma concentrations are strong enzyme-inducing antiepileptic drugs 1:

• Carbamazepine - moderately lowers brivaracetam concentrations (no dose adjustment needed) 1
• Phenytoin - moderately lowers brivaracetam concentrations (no dose adjustment needed) 1
• Phenobarbital/Primidone - moderately lowers brivaracetam concentrations (no dose adjustment needed) 1
• Rifampin - more potent CYP inducer requiring brivaracetam dose adjustment 1
• St. John's Wort - strong enzyme inducer requiring caution 1

Shared Mechanism of Action

Both levetiracetam and brivaracetam bind to synaptic vesicle protein 2A (SV2A), though brivaracetam demonstrates 15- to 30-fold higher binding affinity than levetiracetam 2, 3. Despite this shared target, brivaracetam achieves high SV2A occupancy more rapidly than levetiracetam when administered at therapeutic doses 3. The IC50 of brivaracetam (0.46 μg/mL) is 8.7-fold lower than levetiracetam (4.02 μg/mL), indicating superior binding potency 3.

Clinical Considerations for Switching Between Agents

When Levetiracetam Fails or Causes Intolerable Side Effects

Brivaracetam represents a valid alternative to levetiracetam, with evidence suggesting improved tolerability, particularly for psychiatric adverse events 4. In a retrospective analysis of 102 patients:

• 57.1% of patients who switched from levetiracetam to brivaracetam due to psychiatric side effects reported improved tolerability 4
• 21.7% of patients with quantifiable seizure baseline became newly seizure-free on brivaracetam 4
• 32.6% achieved 50% or greater seizure reduction 4
• Retention rate after 6 months was 80.4% 4

Important Caveat About Psychiatric Side Effects

Patients who develop psychiatric symptoms with levetiracetam remain at risk for similar side effects with brivaracetam, though preliminary data suggest these issues are likely less frequent and less severe 2. In the retrospective study, 23.8% of patients with prior levetiracetam use experienced predominantly psychiatric side effects during brivaracetam treatment 4.

Alternative Antiepileptic Medications

If brivaracetam is not suitable or unavailable, levetiracetam and lamotrigine are preferred first-line options due to their efficacy and favorable tolerability profiles 5:

First-Line Alternatives (Non-Enzyme Inducing)

• Lamotrigine - good antiseizure activity but requires several weeks to reach sufficient drug levels 5
• Lacosamide - may assume a larger role as add-on treatment for patients whose seizure disorder is not controlled by monotherapy 5
• Valproate - still has a firm place in some centers given its efficacy and overall good tolerability, but must not be used in females who may become pregnant 5

Agents to Avoid

Enzyme-inducing anticonvulsants should be avoided in patients with brain tumors and those requiring multiple medications 5:

• Phenytoin - no longer recommended as first choice due to side-effect profile and drug interactions 5
• Phenobarbital - no longer recommended as first choice due to side-effect profile and drug interactions 5
• Carbamazepine - no longer recommended as first choice due to side-effect profile and drug interactions, especially with steroids and various cytotoxic and targeted agents 5

Special Consideration for Oncology Patients

Levetiracetam is considered safer in patients with brain tumors requiring concomitant medications due to its low interaction with cytochromes, unlike carbamazepine, oxcarbazepine, phenobarbital, and phenytoin 5, 6. Antiepileptic therapy appears safe during immunotherapy but can interact with targeted therapy, with the exception of levetiracetam 5.

Practical Switching Strategy

For patients transitioning from levetiracetam to brivaracetam, an overnight switch is feasible and commonly employed 4. Patients who achieved seizure frequency reduction with overnight switching had the highest dose ratio of final brivaracetam dose to levetiracetam (1:10.1), suggesting that previous seizure control was limited by the tolerated levetiracetam dosage 4.

A low starting dose and slow titration schedule help minimize side effects and optimize seizure control, as with all antiepileptic drugs 2.