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

Alternative Medications to Xcopri (Cenobamate) for Seizures

Levetiracetam is the preferred first-line alternative to cenobamate for partial-onset seizures due to its superior efficacy and favorable safety profile. 1

First-Line Alternatives for Partial-Onset Seizures

• Levetiracetam can be administered as a 1,500 mg oral load or rapid IV loading at doses up to 60 mg/kg, with common side effects including fatigue and dizziness, and is available in both tablet and oral solution formulations 1, 2
• Carbamazepine is recommended by the American Academy of Neurology as another preferred first-line alternative, especially in children and adults, with a typical administration of 8 mg/kg oral suspension for loading doses 1, 3
• Lamotrigine has demonstrated good efficacy for partial seizures and is particularly suitable for women of childbearing potential due to lower teratogenic risk compared to valproic acid 1, 3
• Topiramate has proven effectiveness as both monotherapy and adjunctive therapy for partial onset seizures, with FDA approval for patients 2 years and older 1, 4

Second-Line Alternatives

• Lacosamide is available in both oral and IV formulations, with side effects including mild to moderate dizziness, headache, and somnolence, and is particularly useful as an adjunct for partial seizures 1
• Valproic acid can be administered up to 30 mg/kg IV at maximum rate of 10 mg/kg/min, but should be avoided if possible in women of childbearing potential due to teratogenic risk 1, 5
• Phenytoin is a standard antiepileptic that can be administered as 20 mg/kg divided in maximum doses of 400 mg every 2 hours orally, with side effects including hypotension and cardiac dysrhythmias 1, 5
• Gabapentin is typically administered as 900 mg/day oral for 3 days, with side effects including somnolence, dizziness, and fatigue, and is used as an adjunct for partial seizures 1

Comparative Efficacy

• Network meta-analysis shows that for partial seizures, levetiracetam performs significantly better than both carbamazepine and lamotrigine in terms of treatment retention 3
• Lamotrigine performs better than most other alternatives except levetiracetam, while carbamazepine performs significantly better than gabapentin and phenobarbital 3
• For seizure control, phenobarbital and phenytoin demonstrate better efficacy for time to first seizure, but this advantage is offset by their poorer tolerability profiles 3
• Cenobamate (Xcopri) has shown superior efficacy with seizure reduction rates of 55% at 200mg daily compared to older alternatives, but its limited availability necessitates alternatives 6, 7

Special Populations Considerations

• For women with epilepsy, seizures should be controlled with antiepileptic drug monotherapy at minimum effective dose, with valproic acid avoided if possible due to teratogenic risk 1
• For patients with intellectual disability, valproic acid or carbamazepine are preferred over phenytoin or phenobarbital due to lower risk of behavioral adverse effects 1
• For patients with renal impairment, levetiracetam dosing may need adjustment, while gabapentin is primarily eliminated unchanged in urine and requires significant dose reduction 8, 1
• For patients with liver disease, medications metabolized by the liver (like carbamazepine and phenytoin) may require dosage adjustments, while levetiracetam has minimal hepatic metabolism 8, 1

Treatment Algorithm

1. Start with levetiracetam as first-line monotherapy for partial-onset seizures if available and not contraindicated 1, 2
2. If levetiracetam is not tolerated or contraindicated, consider carbamazepine or lamotrigine as alternative first-line options 1, 3
3. If monotherapy fails, consider adjunctive therapy with topiramate, lacosamide, or gabapentin 1, 4
4. For refractory cases, consider valproate, phenytoin, or phenobarbital, weighing their higher side effect profiles against potential benefits 1, 5

Common Pitfalls to Avoid

• Avoid polytherapy when possible to minimize adverse effects and drug interactions; add one antiepileptic at a time 1
• Don't discontinue treatment too early; consider discontinuation only after 2 seizure-free years, taking into account clinical, social, and personal factors 1
• Be aware of potential drug interactions, particularly with enzyme-inducing antiepileptics like carbamazepine, phenytoin, and phenobarbital, which can reduce the effectiveness of concomitant medications 8, 1
• Monitor for specific adverse effects based on the chosen medication: psychiatric effects with levetiracetam, hyponatremia with carbamazepine, rash with lamotrigine, and cognitive effects with topiramate 1, 3