What are alternative treatments to Xcopri (cenobamate) for partial-onset seizures?

Alternative Treatments to Cenobamate (Xcopri) for Partial-Onset Seizures

For patients with partial-onset seizures, carbamazepine is the preferred first-line alternative to cenobamate, especially in children and adults with partial onset seizures, followed by other standard antiepileptic drugs including phenobarbital, phenytoin, and valproic acid. 1

First-Line Alternatives for Partial-Onset Seizures

• Carbamazepine (Tegretol, Equetro): Preferentially recommended for partial onset seizures when available. Typically administered as an 8 mg/kg oral suspension for loading doses, with common side effects including drowsiness, nausea, and dizziness. 1

• Phenytoin (Dilantin, Phenytek): Standard antiepileptic that can be administered as 20 mg/kg divided in maximum doses of 400 mg every 2 hours orally, or 18 mg/kg IV at maximum rate of 50 mg/min. Side effects include hypotension, cardiac dysrhythmias, and risk of purple glove syndrome with IV administration. 1

• Valproic acid (Depacon): Can be administered up to 30 mg/kg IV at maximum rate of 10 mg/kg/min. Should be avoided if possible in women of childbearing potential. Side effects include transient local irritation at injection site, dizziness, thrombocytopenia, and liver toxicity. 1

• Phenobarbital: Recommended as first option in resource-limited settings if availability can be assured due to lower acquisition costs. Dosing typically 10-20 mg/kg; may repeat 5-10 mg/kg at 10 minutes. Side effects include respiratory depression and hypotension. 1

Second-Line Alternatives

• Oxcarbazepine: FDA-approved for monotherapy or adjunctive therapy in partial-onset seizures in adults and as monotherapy in pediatric patients aged 4 years and above. 2

• Topiramate: Effective as both monotherapy and adjunctive therapy for partial-onset seizures. Studies have shown efficacy in both adults and pediatric patients with partial onset seizures. 3

• Lamotrigine: Less likely to be withdrawn than carbamazepine but may be inferior in terms of seizure control. Loading dose of 6.5 mg/kg single oral load if on lamotrigine for >6 months without history of rash. Common side effects include mild, transient nausea and risk of serious rashes. 1, 4

• Levetiracetam (Keppra): Can be administered as 1,500 mg oral load or rapid IV loading at doses up to 60 mg/kg. Side effects include fatigue, dizziness, and rarely pain at infusion site. 1

Newer Alternatives

• Lacosamide (Vimpat): Available in both oral and IV formulations. Side effects include mild to moderate dizziness, headache, back pain, somnolence, and injection site pain. Particularly useful as an adjunct for partial seizures. 1

• Gabapentin (Neurontin, Gralise): Typically administered as 900 mg/day oral (300 mg three times daily) for 3 days. Side effects include somnolence, dizziness, ataxia, and fatigue. Used as an adjunct for partial seizures. 1

Special Considerations

• For patients with intellectual disability: Consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects. 1

• For women with epilepsy: Seizures should be controlled with antiepileptic drug monotherapy at minimum effective dose. Valproic acid should be avoided if possible. Folic acid should be routinely taken when on antiepileptic drugs. 1

• For status epilepticus refractory to benzodiazepines: Valproate appears to work as well as phenytoin or fosphenytoin with fewer adverse effects and can be given more quickly. 1

Treatment Algorithm

1. Start with carbamazepine as first-line monotherapy for partial-onset seizures if available 1
2. If carbamazepine is not tolerated or contraindicated, consider phenytoin, valproic acid (avoid in women of childbearing potential), or newer agents like oxcarbazepine or lamotrigine 1, 2, 4
3. If monotherapy fails, consider adjunctive therapy with levetiracetam, topiramate, lacosamide, or gabapentin 1, 3
4. For refractory cases, valproate or phenobarbital may be considered 1

Common Pitfalls to Avoid

• Avoid polytherapy when possible: Routinely, one antiepileptic should be prescribed at a time to minimize adverse effects and drug interactions. 1

• Don't discontinue treatment too early: Consider discontinuation of antiepileptic drug treatment only after 2 seizure-free years, taking into account clinical, social, and personal factors. 1

• Avoid routine prescription after first unprovoked seizure: Antiepileptic drugs should not be routinely prescribed to adults and children after a first unprovoked seizure. 1

• Monitor for drug interactions: Many antiepileptic medications have significant drug-drug interactions that require careful monitoring and dose adjustments. 5