Xcopri (cenobamate) is a prescription medication used to treat focal-onset seizures in adults. These seizures, also called partial-onset seizures, start in one area of the brain and are the most common type, affecting roughly 60% of the approximately 3 million adults with epilepsy in the United States. Xcopri is typically prescribed when other anti-seizure medications haven’t provided adequate control.
How Xcopri Works
Xcopri targets seizure activity through two complementary pathways. It slows overactive nerve cells by blocking certain sodium channels that allow neurons to fire rapidly and repeatedly. It also enhances the activity of GABA, the brain’s primary calming chemical, making nerve cells less likely to fire out of control. This dual action distinguishes it from many older seizure medications that work through only one of these mechanisms.
How Well It Works
For people whose seizures haven’t responded well to other medications, Xcopri has shown notably strong results. In clinical studies, patients experienced an average seizure reduction of about 57.5%. More striking, 27.5% of patients became completely seizure-free, a rate that’s high for a population with treatment-resistant epilepsy. At doses above 200 mg, the seizure-freedom rate climbed to nearly 44%.
These numbers are particularly meaningful because the patients in these studies had already tried other anti-seizure drugs without adequate control. An estimated 20% to 40% of adults with focal seizures fall into this difficult-to-treat category, so a medication that can push a significant portion toward seizure freedom fills a real gap.
Common Side Effects
Side effects are dose-dependent, meaning they become more common at higher doses. The most frequently reported effects in clinical trials, compared to placebo rates, include:
- Sleepiness: 19% to 37% of patients depending on dose (vs. 11% on placebo)
- Dizziness: 18% to 33% (vs. 15% on placebo)
- Fatigue: 12% to 24% (vs. 7% on placebo)
- Double vision: 6% to 15% (vs. 2% on placebo)
- Headache: 10% to 12% (vs. 9% on placebo)
Most of these effects are related to the central nervous system and tend to be most noticeable during the dose-adjustment period. The slow titration schedule (described below) is specifically designed to minimize these issues.
How the Dose Is Gradually Increased
Xcopri starts at a very low dose of 12.5 mg once daily and increases every two weeks. This slow ramp-up takes about 11 weeks to reach the recommended maintenance dose of 200 mg once daily. If seizure control still isn’t adequate and the medication is well tolerated, the dose can be increased further in 50 mg steps, up to a maximum of 400 mg per day. The gradual approach helps reduce the risk of serious skin reactions and gives your body time to adjust, which is why it’s important not to rush the titration.
Interactions With Other Seizure Medications
Because most people starting Xcopri are already taking other anti-seizure drugs, interactions matter. Xcopri affects the liver enzymes that process many medications, which can raise or lower the levels of other drugs in your system.
Phenytoin levels can nearly double when Xcopri is added, so the phenytoin dose typically needs to be cut by up to half during the titration period. Phenobarbital and clobazam levels also rise, potentially requiring dose reductions. On the other hand, Xcopri lowers the blood levels of lamotrigine (by 21% to 52% depending on dose) and carbamazepine (by about 23%), which may mean those doses need to go up to maintain their effectiveness. Some commonly used seizure medications, including valproic acid and levetiracetam, are not significantly affected.
Beyond epilepsy drugs, Xcopri can alter the effectiveness of other medications processed through the same liver pathways. This includes certain antidepressants, blood thinners, and hormonal contraceptives. Your prescriber will review your full medication list before starting Xcopri and may adjust other doses during the titration period.
Controlled Substance Classification
Xcopri is classified as a Schedule V controlled substance, the lowest category of restriction. This classification reflects its mild potential for abuse and dependence. In studies comparing its effects to other drugs, it produced less “drug liking” than common anti-anxiety medications like alprazolam. Stopping Xcopri abruptly can cause mild withdrawal symptoms such as insomnia, decreased appetite, and memory difficulties, so the dose should be tapered gradually if you and your doctor decide to discontinue it.
Who Can and Cannot Take Xcopri
Xcopri is approved only for adults (18 and older). Its safety and effectiveness in children have not been established. It is also not approved for generalized seizures, the type that affect both sides of the brain from the start, though some practitioners may consider it in certain situations.
People with familial short QT syndrome, a rare heart rhythm condition, should not take Xcopri because the medication can shorten the QT interval on an EKG. A serious but rare skin reaction known as DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) has been reported. The slow dose increases are designed in part to reduce this risk, and any new rash, fever, or swollen lymph nodes during the first few months of treatment should be evaluated promptly.