What is the correct approach to switch anti-seizure medication for a patient who doesn't tolerate Keppra (Levetiracetam)?

Approach to Changing Anti-Seizure Medication for Patients Who Don't Tolerate Levetiracetam (Keppra)

When switching from levetiracetam (Keppra) due to intolerance, lamotrigine or lacosamide should be considered as preferred alternatives due to their favorable efficacy and tolerability profiles. 1, 2

Assessment Before Switching

• Determine the specific reason for intolerance to levetiracetam, as this may guide selection of the next agent (common issues include behavioral side effects, dizziness, and somnolence) 3
• Review the patient's seizure type, as medication selection should be tailored to the specific seizure classification 1
• Evaluate for any comorbidities that might influence medication choice (e.g., pregnancy considerations, intellectual disability) 1

Preferred Alternative Options

First-line alternatives:

• Lamotrigine: Good efficacy with minimal cognitive effects, but requires slow titration to minimize risk of rash 1, 2

  • Start with 25mg daily and increase gradually over 6-8 weeks
  • Particularly beneficial if patient experienced cognitive or behavioral side effects with levetiracetam 4

• Lacosamide: Well-tolerated with both oral and IV formulations available 1, 2

  • Can be rapidly titrated if needed
  • Minimal drug interactions and favorable side effect profile 2

Other evidence-based alternatives:

• Oxcarbazepine: Effective for partial onset seizures with potentially fewer behavioral adverse effects than older agents 2
• Topiramate: Effective broad-spectrum agent, but may cause cognitive slowing and weight loss 5, 4
• Valproic acid: Effective for multiple seizure types, but should be avoided in women of childbearing potential 1
• Zonisamide: Effective for partial seizures with once-daily dosing 2

Switching Process

1. Overlap method (preferred approach):

   • Start the new anti-seizure medication (ASM) while maintaining the current levetiracetam dose
   • Gradually titrate the new medication to an effective dose
   • Once therapeutic levels of the new medication are achieved, slowly taper levetiracetam 1

2. Rapid switch (for severe adverse reactions):

   • If the patient is experiencing severe side effects requiring immediate discontinuation:
     • Consider hospitalization for monitoring during switch if high seizure risk
     • Use loading doses of the new agent when available (e.g., valproate up to 30 mg/kg IV) 1
     • Monitor closely for breakthrough seizures during transition 1

Special Considerations

• Pregnancy: Avoid valproic acid; lamotrigine may be preferred but requires dose adjustments 1
• Intellectual disability: Consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects 1
• Drug interactions: Avoid enzyme-inducing anticonvulsants (carbamazepine, phenytoin, phenobarbital) when possible, especially if the patient is on other medications 1, 4
• Seizure type: For partial onset seizures, carbamazepine may be preferred if available 1

Monitoring After Switch

• Schedule follow-up within 2-4 weeks of initiating the new medication 1
• Assess for seizure control and new adverse effects 1
• Consider serum drug levels if compliance is a concern or to assess for toxicity with certain medications 1
• Educate patients about potential side effects of the new medication and when to seek medical attention 1

Common Pitfalls to Avoid

• Abrupt discontinuation: Never stop levetiracetam suddenly as this may precipitate withdrawal seizures 1
• Inadequate loading: When using loading doses, ensure they are appropriate for the specific agent 1, 6
• Overlooking comorbidities: Consider psychiatric history when selecting alternatives, as some ASMs may worsen mood disorders 1, 4
• Drug interactions: Be aware of potential interactions between ASMs and other medications the patient may be taking 3
• Monotherapy preference: When possible, aim for monotherapy rather than polytherapy to minimize side effects 1