What alternative medication can be used for a patient who does not tolerate Keppra (levetiracetam)?

Alternative Anti-Seizure Medications for Levetiracetam Intolerance

When a patient does not tolerate Keppra (levetiracetam), lamotrigine should be considered as the preferred first-line alternative for focal epilepsy, while lacosamide represents another favorable option. 1

Preferred Alternative Agents

For Focal Epilepsy

• Lamotrigine is the recommended alternative based on superior efficacy and tolerability compared to levetiracetam in head-to-head trials, with better seizure remission rates and fewer treatment failures. 1, 2
• Lacosamide represents another preferred alternative due to its favorable efficacy and tolerability profile. 1
• Zonisamide may be considered, though it showed inferior outcomes compared to lamotrigine in the SANAD II trial, with higher treatment failure rates (46% vs 60% hazard ratio for treatment failure). 2

For Generalized Epilepsy

• Valproate remains superior to levetiracetam for generalized epilepsy, with significantly better seizure remission rates (hazard ratio 1.68 for 12-month remission). 2
• However, valproate must be avoided in women of childbearing potential due to teratogenicity concerns; in this population, lamotrigine becomes the preferred alternative despite requiring dose adjustments. 1

Switching Strategy

The Overlap Method (Preferred Approach)

• Initiate the new anti-seizure medication while maintaining the current levetiracetam dose, then gradually titrate the new agent to an effective dose before tapering levetiracetam. 1
• Never stop levetiracetam abruptly, as this may precipitate withdrawal seizures. 1
• Schedule follow-up within 2-4 weeks of initiating the new medication to assess seizure control and monitor for adverse effects. 1

For Severe Adverse Reactions

• Consider hospitalization for monitored transition when patients experience severe reactions such as significant thrombocytopenia or severe bruising. 1
• Loading doses of the new agent may be used when available to maintain seizure protection during more rapid levetiracetam discontinuation. 1

Medication-Specific Considerations

Lamotrigine

• Demonstrated superiority over levetiracetam in per-protocol analysis with hazard ratio of 1.32 for time to 12-month remission. 2
• Superior for treatment failure outcomes (hazard ratio 0.60 vs levetiracetam). 2
• Adverse reactions reported in 33% of patients, lower than levetiracetam's 44%. 2
• More cost-effective than levetiracetam, as levetiracetam was both more costly and less effective in economic analysis. 2

Carbamazepine (Alternative Option)

• Controlled-release carbamazepine showed equivalent seizure freedom rates to levetiracetam (72.8% vs 73.0% achieving 6-month seizure freedom). 3
• However, carbamazepine causes significantly more cognitive impairment, with worse attention deficit, frontal executive functions, and functional scales compared to levetiracetam. 4
• Higher withdrawal rates for adverse events (19.2% vs 14.4% with levetiracetam). 3

Critical Pitfalls to Avoid

Drug Interaction Considerations

• Avoid enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamazepine) when possible, as they significantly affect cytochrome P450 metabolism and interact with numerous chemotherapeutic agents including irinotecan, gefitinib, erlotinib, and temsirolimus. 5
• Levetiracetam's advantage was its lack of significant drug interactions, so when switching, consider non-enzyme-inducing alternatives like lamotrigine, lacosamide, or topiramate. 5, 6

Monitoring Requirements

• Assess serum drug levels if compliance concerns arise or to evaluate for toxicity with certain medications. 1
• Monitor for additive sedative effects when combining with other CNS-active medications. 6
• Educate patients about potential side effects of the new medication and when to seek immediate medical attention. 1

Treatment Philosophy

• Aim for monotherapy rather than polytherapy to minimize side effects and drug interactions. 1
• Tailor medication selection to the specific seizure classification (focal vs generalized). 1
• Evaluate for comorbidities that influence medication choice, including pregnancy considerations and intellectual disability. 1