SAFETY

The safety profile of XCOPRI offers more than a decade of clinical trial and real-world 
experience, including long-term retention data.

Actor portrayals.

The safety profile of XCOPRI offers more than a decade of clinical trial and real-world 
experience, including long-term retention data.

10+ years of clinical trial and real-world experience

Well-studied safety with over 220,000 patients prescribed worldwide*

Most common adverse reactions observed in patients during XCOPRI (cenobamate tablets) CV clinical trials include1†:

  • Discontinuation rates due to adverse reactions were 11% (100 mg), 9% (200 mg), and 21% (400 mg) for patients on XCOPRI compared with 4% for patients on placebo1
  • No dosage changes to concomitant anti-seizure medications (ASMs) were allowed during the double-blind clinical trials2,3
  • XCOPRI makes the concentration of some drugs increase. Consider decreasing the dosage of clobazam, phenytoin, and phenobarbital early in XCOPRI titration1
*Worldwide new-to-brand cenobamate prescriptions as of June 2025. Source: IQVIA.
†Safety information is based on pooled data from Study 1 and Study 2.

XCOPRI was studied across 2 multicenter, randomized, double-blind, placebo-controlled trials in adult patients with partial-onset seizures with or without secondary generalization.1

Pills

1-3

concomitant ASMs were not adequately controlling patients at baseline1‡

Patients

PLACEBO

Patients in the placebo arm remained on their current ASM2,3

of patients were taking 2 or more concomitant ASMs1

Calendar

24YEARS

was the approximate duration of epilepsy for patients in both studies1

Brain

~9SEIZURES

per 28 days was the median baseline seizure frequency for patients in both studies1

‡The more frequently used ASMs were levetiracetam, lamotrigine, valproate or valproic acid, carbamazepine, oxcarbazepine, clobazam, lacosamide, and topiramate.2,3

Cognition and weight with XCOPRI

Neuro-psychiatric

Based on a post hoc analysis of pooled populations across phase 2 and phase 3 studies 

Rates of cognitive TEAEs observed with XCOPRI were 2.3% vs 0.9% with placebo4§

Limitations: Cognitive symptoms were evaluated using non-standardized measures including spontaneous patient self-reporting, which may have led to underreporting of mild or intermittent symptoms. Baseline cognitive comorbidities were assessed retrospectively and could not be directly compared with TEAEs. Potential confounding effects from concomitant ASMs further limit interpretation of cognitive findings.

Scale

Low rates of weight change reported with XCOPRI in pivotal trials1

XCOPRI (3/442) vs placebo (0/216)

§Patients with focal epilepsy were assessed on memory impairment, word-finding difficulty, mathematical difficulty, and disturbances in attention.

TEAEs=treatment-emergent adverse events.

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Long-term retention rates5

Pooled data from the clinical development program:

At 5 years, the majority of patients remained on treatment

Long-term retention rates

About the analysis:

These retention data are based on Kaplan-Meier estimates of time to discontinuation of open-label XCOPRI in the pooled population from 3 clinical studies. Conclusions of long-term efficacy and safety should not be drawn based on these data.

80% of patients were on 2-3 concomitant ASMs at the start of open-label XCOPRI treatment. In this pooled population, the median duration of XCOPRI exposure was 2.8 years, with a median XCOPRI modal dose of 200 mg/day.

Pavel Klein, MB BChir, FAAN, FAES

“Adjustments in the dosage of medications in patients taking multiple drugs can help optimize efficacy while minimizing side effects.”

– Pavel Klein, MB BChir, FAAN, FAES

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References: 1. XCOPRI [package insert]. Paramus, NJ: SK Life Science, Inc. 2. Chung SS, French JA, Kowalski J, et al. Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures. Neurology. 2020;94(22):e2311-e2322. 3. Krauss GL, Klein P, Brandt C, et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicentre, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020;19(1):38-48. 4. Krauss GL, Chung SS, Ferrari L, Stern S, Rosenfeld WE. Cognitive and psychiatric adverse events during adjunctive cenobamate treatment in phase 2 and phase 3 clinical studies. Epilepsy Behav. 2024;151:109605. 5. Sander JW, Rosenfeld WE, Halford JJ, Steinhoff BJ, Biton V, Toledo M. Long-term individual retention with cenobamate in adults with focal seizures: pooled data from the clinical development program. Epilepsia. 2022;63(1):139-149.
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INDICATION

XCOPRI is indicated for the
treatment of partial-onset
seizures in adult patients.

Important Safety Information
and indication

CONTRAINDICATIONS
XCOPRI is contraindicated in patients with hypersensitivity to cenobamate or any of the ingredients in the product.
XCOPRI is contraindicated in patients with Familial Short QT syndrome.

Collapse IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION and INDICATION for XCOPRI® (cenobamate tablets) CV

CONTRAINDICATIONS

XCOPRI is contraindicated in patients with hypersensitivity to cenobamate or any of the ingredients in the product. 

XCOPRI is contraindicated in patients with Familial Short QT syndrome.

WARNINGS AND PRECAUTIONS

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including XCOPRI. DRESS has been reported, including one fatality, when XCOPRI is titrated rapidly (weekly or faster titration). No cases of DRESS were reported in an open-label safety study of 1339 partial-onset seizure patients when XCOPRI was initiated at 12.5 mg/day and titrated every two weeks. This finding does not establish that the risk of DRESS is prevented by a slower titration; however, XCOPRI should be initiated at 12.5 mg once daily and titrated every two weeks. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement. Eosinophilia is often present. If such signs or symptoms are present, the patient should be evaluated immediately. XCOPRI should be discontinued immediately and not restarted if an alternative etiology for the signs or symptoms cannot be established.

QT Shortening: XCOPRI can cause shortening of the QT interval. Caution should be used when administering XCOPRI and other drugs that shorten the QT interval as there may be a synergistic effect on the QT interval that would increase the QT shortening risk.

Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including XCOPRI, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients, their caregivers, and/or families to be alert for these behavioral changes and report them immediately to a healthcare provider.

Liver Injury: Clinically significant liver injury has occurred in patients taking XCOPRI. Obtain serum transaminases (ALT and AST) and total bilirubin, if not recently available (i.e., within 3 months) before initiating XCOPRI, and during treatment if clinically indicated. Monitor patients for signs and symptoms of any hepatic injury during treatment. Discontinue XCOPRI in patients with evidence of liver injury in the absence of an alternative etiology.

Neurological Adverse Reactions: XCOPRI can cause dose-dependent increases in the neurologic adverse reactions including dizziness, diplopia, disturbance in gait and coordination, somnolence, and fatigue.

Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of XCOPRI is known.

Withdrawal of AEDs: As with all antiepileptic drugs, XCOPRI should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.

MOST COMMON ADVERSE REACTIONS

In adult adjunctive therapy placebo-controlled clinical studies, the most common adverse reactions that occurred in XCOPRI-treated patients (incidence at least 10% and greater than placebo) were somnolence, dizziness, fatigue, diplopia, headache.

DOSING CONSIDERATIONS

Dosage adjustment of XCOPRI or other concomitant medications may be necessary.

  • Consider gradually reducing phenytoin dosages by up to 50% during initial titration.
  • Consider reducing dosages of phenobarbital and clobazam as needed when used concomitantly with XCOPRI.
  • When XCOPRI and carbamazepine or lamotrigine are taken concomitantly, consider increasing dosages as needed of carbamazepine or lamotrigine.
  • Consider increasing dosages as needed of drugs which are CYP2B6 and CYP3A substrates and decreasing dosages as needed of drugs which are CYP2C19 substrates.
  • Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with XCOPRI. Women should use additional or alternative non-hormonal birth control.

Dosage reduction of XCOPRI may be considered in patients with mild to moderate and severe renal impairment. XCOPRI is not recommended in end-stage renal disease.

The maximum recommended daily dose is 200 mg for patients with mild or moderate hepatic impairment. XCOPRI is not recommended in patients with severe hepatic impairment.

DRUG ABUSE

XCOPRI is a Schedule V controlled substance.

INDICATION

XCOPRI is indicated for the treatment of partial-onset seizures in adult patients.

Please see full Prescribing Information.