What is the recommended approach to switch from Keppra (Levetiracetam) to another antiepileptic drug due to bruising?

Switching from Levetiracetam 750mg BID Due to Bruising

Use the overlap method to transition from levetiracetam to lamotrigine or lacosamide, which are the preferred alternatives when levetiracetam is not tolerated. 1

Immediate Assessment

Before switching, confirm that bruising is indeed related to levetiracetam and not another cause:

• Check platelet count and coagulation studies to rule out thrombocytopenia or other hematologic abnormalities, as levetiracetam can rarely cause hematologic adverse effects 2, 3
• Review all concurrent medications for drug interactions or other agents that could contribute to bruising
• Document seizure type and frequency to guide selection of the most appropriate alternative medication 1

Preferred Alternative Medications

Lamotrigine is the first-line alternative for most patients switching from levetiracetam due to intolerance, based on superior efficacy and tolerability data 1, 4:

• Lamotrigine demonstrated superiority over levetiracetam in time to 12-month remission (HR 1.32,95% CI 1.05-1.66) and time to treatment failure (HR 0.60,95% CI 0.46-0.77) 4
• Fewer adverse reactions compared to levetiracetam (33% vs 44%) 4
• More cost-effective than levetiracetam 4

Lacosamide is an equally acceptable alternative with favorable tolerability 1

Avoid valproate if the patient is a woman of childbearing potential due to teratogenicity concerns 1

Switching Protocol: The Overlap Method

Start the new medication while maintaining current levetiracetam dose, then gradually taper levetiracetam after the new agent reaches therapeutic levels 1:

For Lamotrigine:

• Week 1-2: Start lamotrigine 25mg daily while continuing levetiracetam 750mg BID
• Week 3-4: Increase lamotrigine to 50mg daily, continue levetiracetam 750mg BID
• Week 5: Increase lamotrigine to 100mg daily, begin tapering levetiracetam to 500mg BID
• Week 6: Increase lamotrigine to 200mg daily (target dose), reduce levetiracetam to 250mg BID
• Week 7: Continue lamotrigine 200mg daily, reduce levetiracetam to 250mg daily
• Week 8: Continue lamotrigine 200mg daily, discontinue levetiracetam

This slow titration is critical because lamotrigine requires gradual dose escalation to minimize risk of serious rash 5.

For Lacosamide:

• Week 1: Start lacosamide 50mg BID while continuing levetiracetam 750mg BID
• Week 2: Increase lacosamide to 100mg BID, begin tapering levetiracetam to 500mg BID
• Week 3: Continue lacosamide 100mg BID (or increase to 150mg BID if needed), reduce levetiracetam to 250mg BID
• Week 4: Continue lacosamide at target dose, discontinue levetiracetam

Critical Pitfalls to Avoid

Never abruptly discontinue levetiracetam, as this can precipitate withdrawal seizures 1:

• Always maintain therapeutic levels of at least one anti-seizure medication throughout the transition
• Taper levetiracetam gradually over at least 2-4 weeks 1

Do not rush lamotrigine titration to avoid Stevens-Johnson syndrome and toxic epidermal necrolysis 5

Avoid polytherapy when possible - the goal is monotherapy with the new agent to minimize side effects and drug interactions 1, 5

Monitoring During Transition

Schedule follow-up within 2-4 weeks of initiating the new medication 1:

• Assess for seizure control and breakthrough seizures
• Monitor for new adverse effects specific to the new medication
• Verify resolution of bruising after levetiracetam discontinuation
• Consider serum drug levels if compliance is uncertain 1

Educate the patient about warning signs requiring immediate medical attention 1:

• For lamotrigine: any new rash (stop medication immediately and contact physician)
• For lacosamide: dizziness, cardiac symptoms, or PR interval prolongation
• Any increase in seizure frequency or new seizure types

Special Considerations for Severe Reactions

If bruising is severe or associated with significant thrombocytopenia:

• Consider hospitalization for monitored transition with loading doses of the new agent when available 6
• More rapid levetiracetam discontinuation may be warranted, but maintain seizure protection with adequate dosing of the new medication 6