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Xcopri (cenobamate)
Xcopri is a prescription medicine for treating partial-onset seizures in adults.
It’s unknown if Xcopri is safe and effective for children.
What are the side effects of Xcopri?
Xcopri may cause serious side effects, including:
- problems with the electrical system of the heart (QT shortening). Call your healthcare provider if you have symptoms of QT shortening including fast heartbeat (heart palpitations) that last a long time or fainting.
- nervous system problems. Xcopri may affect your nervous system. Symptoms of nervous system problems include:
- dizziness
- trouble walking or with coordination
- feeling sleepy and tired
- trouble concentrating, remembering, and thinking clearly
- vision problems
The most common side effects of Xcopri include:
- feeling sleepy and tired
- dizziness
- double vision
- headache
Tell your healthcare provider if you have any side effects that bother you or do not go away. These are not all the possible side effects of Xcopri.
For more information, ask your healthcare provider or pharmacist. Contact your doctor for medical advice about side effects. Report side effects to FDA at 1-800-FDA-1088.
Does Xcopri cause addiction or withdrawal symptoms?
Drug Abuse And Dependence
Controlled Substance
Xcopri contains cenobamate and is a Schedule V controlled substance.
Abuse
- Abuse is the intentional, non-therapeutic use of a drug for its desirable psychological or physiological effects. In a human abuse potential study conducted in recreational sedative abusers (n=39), single doses of Xcopri (200 mg and 400 mg) were compared to placebo.
- Xcopri at single doses of 400 mg produced statistically greater positive subjective measures compared to placebo.
- Euphoric mood occurred at a greater extent with Xcopri (400 mg) (8%) than with placebo (0%).
- Phase 1 multiple ascending dose studies showed rates of euphoria and feeling drunk of about 3% and disturbance in attention of about 5% in subjects who received supratherapeutic doses of cenobamate.
- In Phase 2 and 3 studies in subjects with epilepsy, euphoric mood, confusional state, and sedation occurred at low rates in subjects who received Xcopri (0.5-2.5%).
Dependence
- Physical dependence is a state that develops as a result of physiological adaptation to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
- Clinical studies indicate that Xcopri may cause physical dependence and lead to a withdrawal syndrome characterized by insomnia, decreased appetite, depressed mood, tremor, and amnesia. Xcopri should be withdrawn gradually.
What is the dosage for Xcopri?
Important Administration Instructions
- Xcopri may be taken any time with or without food. Swallow tablets whole with liquid.
- Do not crush or chew.
General Dosing Recommendations
Monotherapy And Adjunctive Therapy
- Xcopri is taken orally once daily.
- The recommended dosage and titration, which should not be exceeded due to the potential for serious adverse reactions, are included in Table 1.
Table 1: Recommended Dosage for Partial-Onset Seizures in Adults
| Initial Dosage | |
| Week 1 and 2 | 12.5 mg once daily |
| Titration Regimen | |
| Week 3 and 4 | 25 mg once daily |
| Week 5 and 6 | 50 mg once daily |
| Week 7 and 8 | 100 mg once daily |
| Week 9 and 10 | 150 mg once daily |
| Maintenance Dosage | |
| Week 11 and thereafter | 200 mg once daily |
| Maximum Dosage | |
| If needed based on clinical response and tolerability, dose may be increased above 200 mg by increments of 50 mg once daily every two weeks to 400 mg. | 400 mg once daily |
Dosage Modifications In Patients With Hepatic Impairment
- For patients with mild to moderate (5-9 points on Child-Pugh assessment) hepatic impairment, the maximum recommended dosage is 200 mg once daily.
- Xcopri is not recommended for use in patients with severe hepatic impairment.
Discontinuation Of Xcopri
- If Xcopri is discontinued, the dosage should be gradually reduced over a period of at least 2 weeks, unless safety concerns require abrupt withdrawal.
What drugs interact with Xcopri?
Effect Of Xcopri On Other Drugs
Table 5 summarizes the effect of Xcopri on other drugs.
Table 5: Pharmacokinetic Drug Interactions
| Drug or Substrate Type | Effect of Xcopri on Drug or Substrate | Clinical Recommendation |
| Antiepileptic Drugs | ||
| lamotrigine | ↓ plasma concentrations | Increase the dosage of lamotrigine or carbamazepine, as needed, when used concomitantly with Xcopri due to potential reduced efficacy. |
| carbamazepine | ↓ plasma concentrations | |
| phenytoin | ↑plasma concentrations | Gradually decrease phenytoin dosage by up to 50% as Xcopri is being titrated due to potential 2-fold increase in phenytoin levels. |
| phenobarbital | ↑ plasma concentrations | Consider a reduction in dosage of phenobarbital or clobazam, as clinically appropriate, when used concomitantly with Xcopri due to potential increase in risk of adverse reactions. |
| desmethylclobazam, the active metabolite of clobazam | ↑plasma concentrations | |
| CYP2B6 Substrates | ↓ plasma concentrations | Increase the dosage of CYP2B6 or CYP3 A4 substrates, as needed, when used concomitantly with Xcopri due to potential reduced efficacy. |
| CYP3A Substrates | ↓ plasma concentrations | |
| Oral contraceptives | ↓ plasma concentrations | Use additional or alternative non-hormonal birth control while taking Xcopri due to potential reduced efficacy of oral contraceptives. |
| CYP2C19 Substrates | ↑ plasma concentrations | Consider a reduction in dosage of CYP2C19 substrates, as clinically appropriate, when used concomitantly with Xcopri due to potential increase in risk of adverse reactions. |
Drug That Shorten The QT Interval
- Xcopri can shorten the QT interval, so caution should be used when administering Xcopri and other drugs that shorten the QT interval.
CNS Depressants And Alcohol
- Concomitant use of Xcopri with other CNS depressants, including alcohol, may increase the risk of neurological adverse reactions, including sedation and somnolence.
Is Xcopri safe to use while pregnant or breastfeeding?
- There are no adequate data on the developmental risk associated with the use of Xcopri in pregnant women.
- There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as Xcopri, during pregnancy.
- Encourage women who are taking Xcopri during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.
Summary
Xcopri is a prescription medicine for treating partial-onset seizures in adults. It’s unknown if Xcopri is safe and effective for children. Xcopri contains cenobamate and is a Schedule V controlled substance.
