What is the risk of seizure exacerbation when switching from Keppra (levetiracetam) to Brevict (brivaracetam)?

Risk of Seizure When Switching from Keppra to Briviact

Switching from Keppra (levetiracetam) to Briviact (brivaracetam) is generally safe with minimal risk of seizure exacerbation when done properly, especially with an appropriate dose conversion ratio of 10:1 to 15:1.

Pharmacological Relationship and Conversion

Brivaracetam and levetiracetam are structurally related antiepileptic drugs that both target the synaptic vesicle protein 2A (SV2A), though brivaracetam has approximately 15-30 times higher affinity for this target. This relationship allows for a relatively straightforward transition between medications:

• The recommended conversion ratio is 10:1 to 15:1 (levetiracetam:brivaracetam)
• Example: Levetiracetam 1000mg daily would convert to brivaracetam 100mg daily
• An immediate overnight switch is feasible and commonly performed 1

Efficacy and Seizure Control During Transition

Clinical evidence suggests that seizure control is generally maintained when switching between these medications:

• In a retrospective study of patients switched from levetiracetam to brivaracetam, 32.6% achieved ≥50% seizure reduction and 21.7% became newly seizure-free 1
• Only 21.7% of patients experienced an increase in seizure frequency after switching 1
• The FDA-approved brivaracetam dosing starts at 50mg twice daily (100mg/day) for adults, with maintenance dosing ranging from 25-100mg twice daily (50-200mg/day) 2

Risk Factors for Breakthrough Seizures

Several factors may increase the risk of breakthrough seizures when switching medications:

• Inadequate dose conversion (using too low a brivaracetam dose)
• Abrupt discontinuation of levetiracetam without proper titration of brivaracetam
• Patients with poorly controlled epilepsy at baseline
• History of frequent breakthrough seizures with medication changes

Minimizing Risk During Transition

To minimize the risk of seizure exacerbation when switching:

1. Use appropriate dose conversion: Maintain a 10:1 to 15:1 ratio (levetiracetam:brivaracetam) 1
2. Consider overnight switch: An immediate switch is feasible for most patients 3, 4
3. Monitor closely: Especially during the first few weeks after transition
4. Avoid abrupt withdrawal: If not doing an immediate switch, gradually increase brivaracetam while decreasing levetiracetam
5. Be cautious with hepatic impairment: Reduce brivaracetam dosage in patients with hepatic impairment 2

Special Considerations

Generic vs. Brand Formulations

There have been reports of breakthrough seizures when switching from brand-name levetiracetam (Keppra) to generic levetiracetam 5, 6. However, this concern does not directly apply to switching between levetiracetam and brivaracetam, which are different molecules.

Psychiatric Side Effects

One potential benefit of switching from levetiracetam to brivaracetam is improved psychiatric tolerability:

• 57.1% of patients switched due to psychiatric side effects reported improved tolerability with brivaracetam 1
• Only 23.8% of patients with prior levetiracetam use experienced psychiatric side effects with brivaracetam 1

Conclusion

When performed with appropriate dosing and monitoring, the risk of seizure exacerbation when switching from Keppra to Briviact is relatively low. The high affinity of brivaracetam for the SV2A target and the ability to perform an immediate switch with proper dose conversion contribute to maintaining seizure control during transition.