Tablet (Xcopri)
- Strengths
- 12.5, 25, 50, 100, 150, 200 mg
- Product note
- Titration packs combine these strengths. Label permits crushing in water for oral/NG administration; this is not a bottled liquid with a fixed concentration.
Cenobamate
Xcopri
DailyMed-verified antiseizure indications
Indication / use
- Label / evidence summary
- Xcopri: focal-onset (partial-onset) seizures in adults.
- Role
- Maintenance
- Class
- Sodium-current inhibition plus non-benzodiazepine GABA-A potentiation
Indications checked 26 September 2026. Product, route, age, and treatment-role limits apply. A DailyMed listing alone does not establish FDA approval.
- Xcopri tablet U.S. label
Focal seizures · 18 years and older · Maintenance
Formulations & strengths
U.S. products unless another country is named. Strengths are per unit or stated volume.
Brand & formulation labels
Each link names the product and formulation it covers. Archived labels do not establish current availability.
Dosing & administration
- Adult / product-specific schedule
- 12.5 mg once daily for 2 weeks, then 25 mg daily for 2 weeks; titrate every 2 weeks to 200 mg/day. Maximum 400 mg/day.
- Pediatric
- Safety and effectiveness not established in pediatric patients.
- Titration / repeat dosing
- Weeks 1–2: 12.5 mg daily; 3–4: 25 mg; 5–6: 50 mg; 7–8: 100 mg; 9–10: 150 mg; week 11 onward: 200 mg. If needed, increase by 50 mg/day every 2 weeks to maximum 400 mg/day. Do not accelerate.
Practical administration
- Product instructions
- XCOPRI may be taken with or without food. Current labeling allows tablets to be crushed in water for oral or nasogastric administration; use the label’s preparation and rinse volumes immediately.
Dose adjustment & concentrations
- Renal impairment
- Use caution in mild–moderate/severe impairment; not recommended in ESRD.
- Hepatic impairment
- Lower maximum dose in mild–moderate impairment; not recommended in severe impairment.
- Serum reference information
- No established therapeutic range
Safety
- Boxed warning
- No boxed warning.
- Contraindications
- Familial short-QT syndrome; hypersensitivity to cenobamate or ingredients.
- Serious precautions & monitoring
- Clinically significant liver injury reported. Obtain ALT, AST and total bilirubin before starting unless available within 3 months; repeat when clinically indicated. Investigate hepatic symptoms promptly. DRESS risk requires slow titration; QT shortening and additive CNS effects require review.
Common / selected adverse effects
- Somnolence
- Dizziness
- Fatigue
- Diplopia
- Headache
Xcopri: pooled placebo-controlled adjunctive focal-seizure trials, adults (label §6.1, Table 4)
| Effect | 100 mg/day (n=108) | 200 mg/day (n=223) | 400 mg/day (n=111) | Placebo (n=216) |
|---|---|---|---|---|
| Somnolence | 19% | 22% | 37% | 11% |
| Dizziness | 18% | 22% | 33% | 15% |
| Fatigue | 12% | 14% | 24% | 7% |
| Diplopia | 6% | 7% | 15% | 2% |
Drug interactions: toxicity & clinical action
| Partner / combination | Clinical effect | Clinical action |
|---|---|---|
| Phenytoin | Concentration can approximately double; ataxia, nystagmus and sedation. | Gradually reduce phenytoin by up to 50% during cenobamate titration as directed by label and levels. |
| Clobazam / phenobarbital | Active clobazam metabolite or phenobarbital exposure rises; prolonged sedation. | Consider partner dose reductions; monitor during titration and after changes. |
| Carbamazepine / lamotrigine | Parent concentrations fall, but combined sodium-channel effects can still cause dizziness/ataxia. | Adjust to clinical response and tolerability, not a concentration alone. |
| Hormonal contraceptives / other QT-shortening or sedating drugs | Lower contraceptive exposure; additive QT shortening or CNS depression. | Use additional/alternative nonhormonal contraception and review cardiac/sedative combinations. |
Pregnancy & contraception
- Fetal / neonatal risk
- Human cenobamate pregnancy data are inadequate. Animal studies found developmental toxicity at clinically relevant exposures.
- Contraception
- Cenobamate can reduce oral contraceptive effectiveness. Use additional or alternative nonhormonal contraception.
Clinical evidence
Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.
Direct pivotal trial
Trial summary
- Study design / duration
- Two randomized, double-blind, placebo-controlled adult adjunctive focal-seizure studies: one flexible 200-mg target trial and one 100/200/400-mg dose-response trial, each following an 8-week baseline.
- Primary endpoint
- Study 1, adults with focal seizures on 1–3 ASMs: 200 mg/day 55.6% reduction (n=113) vs placebo 21.5% (n=108), combined 6-week titration + 6-week maintenance. Study 2: 100/200/400 mg/day reductions 36.3/55.2/55.3% vs 24.3% placebo, 6-week titration + 12-week maintenance.
- Results
- Two pivotal randomized phase 2 studies supported approval. In one, median focal-seizure reductions were 55.6% at 200 mg/day versus 21.5% with placebo. In the dose-response trial, reductions were 36.3%, 55.2% and 55.3% at 100, 200 and 400 mg/day versus 24.3% with placebo.
- Responder rate
- ≥50% responder distributions are shown by dose in label Figures 1–2; a single pooled percentage is not presented.
- Seizure freedom
- Study 2 maintenance only: no focal seizures in 4/102 (4%), 11/98 (11%), 20/95 (21%) at 100/200/400 mg/day vs 1/102 (1%) placebo. Not sustained long-term seizure freedom.
Trial publications
Mechanism of action
- The label describes voltage-gated sodium-current inhibition and GABA-A positive allosteric modulation; their relative contributions to human seizure control are unresolved.
- Rat-neuron experiments show preferential inhibition of persistent sodium current under the tested conditions; this does not mean all transient sodium currents are unaffected.
- Experimental GABA-A potentiation occurs independently of the classical benzodiazepine site and can enhance tonic inhibition. It is not a benzodiazepine despite sharing a GABA-A target.
Pharmacology
Adult values unless specified. Vd/F denotes apparent oral distribution volume.
Pharmacokinetics
- Bioavailability
- At least 88% of an oral dose is absorbed. This absorption estimate is not an established absolute bioavailability value. Food does not meaningfully alter exposure.
- Elimination half-life
- Approximately 50–60 hours (apparent terminal half-life).
- Volume of distribution
- Apparent oral Vd/F approximately 40–50 L.
- Active metabolite(s)
- No clinically established active metabolite. Unchanged cenobamate accounts for >98% of circulating drug-related AUC in the radiolabel study.
- Active-metabolite half-life
- Not applicable — no clinically established active metabolite.
- Protein binding
- ~60%
- Metabolism / elimination
- UGT2B7; CYP2E1, 2A6, 2B6; minor CYP2C19/3A4/5
Glucuronidation and oxidation form metabolites.
Molecular structure
NIH PubChem structure and record ↗
Product history
- Initial U.S. approval
- 2019
- Brands
- Xcopri
- Manufacturer / marketer
- SK Life Science (Xcopri)
- Generic availability
- No
- Related drugs
- Dual-mechanism ASM; sodium-current effects overlap with sodium-channel blockers.
Sources & review status
Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 8/2025. This is a draft reference; final review is pending.