Alternative Treatments to Cenobamate for Partial-Onset Seizures

First-Line Alternatives for Partial-Onset Seizures

The American Academy of Neurology recommends carbamazepine as the preferred first-line alternative to cenobamate for partial-onset seizures, especially in children and adults, with a typical administration of 8 mg/kg oral suspension for loading doses, and common side effects including drowsiness, nausea, and dizziness 1, 2, 3, 4
Phenytoin is a 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, with side effects including hypotension, cardiac dysrhythmias, and risk of purple glove syndrome with IV administration 5, 6
Valproic acid can be administered up to 30 mg/kg IV at maximum rate of 10 mg/kg/min, and should be avoided if possible in women of childbearing potential, with side effects including transient local irritation at injection site, dizziness, thrombocytopenia, and liver toxicity 3, 5, 7
Phenobarbital is recommended as a first option in resource-limited settings if availability can be assured due to lower acquisition costs, with dosing typically 10-20 mg/kg, and side effects including respiratory depression and hypotension 1, 3, 7

Levetiracetam can be administered as 1,500 mg oral load or rapid IV loading at doses up to 60 mg/kg, with side effects including fatigue, dizziness, and rarely pain at infusion site 5, 7
Lacosamide is available in both oral and IV formulations, with side effects including mild to moderate dizziness, headache, back pain, somnolence, and injection site pain, and is particularly useful as an adjunct for partial seizures 5
Gabapentin is typically administered as 900 mg/day oral for 3 days, with side effects including somnolence, dizziness, ataxia, and fatigue, and is used as an adjunct for partial seizures 8

For patients with intellectual disability, the American Academy of Neurology recommends considering valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects 3, 4
For women with epilepsy, seizures should be controlled with antiepileptic drug monotherapy at minimum effective dose, valproic acid should be avoided if possible, and folic acid should be routinely taken when on antiepileptic drugs 3, 4
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 7, 9

The American Academy of Neurology recommends starting with carbamazepine as first-line monotherapy for partial-onset seizures if available 1, 4
If carbamazepine is not tolerated or contraindicated, consider phenytoin, valproic acid, or newer agents like lamotrigine 3
If monotherapy fails, consider adjunctive therapy with levetiracetam, topiramate, lacosamide, or gabapentin 8, 5
For refractory cases, valproate or phenobarbital may be considered 7, 9

The American Academy of Neurology recommends avoiding polytherapy when possible, and routinely prescribing one antiepileptic at a time to minimize adverse effects and drug interactions 3
Don't discontinue treatment too early, and consider discontinuation of antiepileptic drug treatment only after 2 seizure-free years, taking into account clinical, social, and personal factors 3, 4
Antiepileptic drugs should not be routinely prescribed to adults and children after a first unprovoked seizure 3

For patients with renal impairment, levetiracetam dosing may need adjustment, while gabapentin is primarily eliminated unchanged in urine and requires significant dose reduction, as recommended by guidelines from the MMWR Recommendations and Reports 10
For patients with liver disease, medications metabolized by the liver, such as carbamazepine and phenytoin, may require dosage adjustments, while levetiracetam has minimal hepatic metabolism, according to the MMWR Recommendations and Reports 10

The American Academy of Neurology and other guideline societies recommend being aware of potential drug interactions, particularly with enzyme-inducing antiepileptics like carbamazepine, phenytoin, and phenobarbital, which can reduce the effectiveness of concomitant medications, as noted in the Annals of Oncology 11