• Xcopri is a brand (trade) name for cenobamate which may be used to treat partial-onset seizures.
• The exact way Xcopri works is unknown, but research has shown it reduces repetitive neuronal firing by inhibiting voltage-gated sodium currents and it positively modulates the γ-aminobutyric acid (GABAA) ion channel.
• Xcopri belongs to the class of medicines known as carbamate anticonvulsants. It may also be called an anti-seizure medication or an antiepileptic.

• May be used to treat partial-onset seizures in adults.
• May be used alone or in combination with other anti-seizure medications.
• Some people have reported having their seizures decrease to zero after taking Xcopri.
• Only needs to be taken once a day. Can be taken at any time of the day.
• May be taken with or without food.
• Available in 12.5mg, 25mg, 50mg, 100mg, 150mg, and 200mg tablets.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Clumsiness (ataxia), dizziness, drowsiness, double vision, nystagmus (repetitive, uncontrolled eye movements), headache, and vertigo (the sensation that the environment around you is moving or spinning) are the most common side effects reported with Xcopri. Other side effects such as diarrhea, nausea, constipation, and blurred vision have also been reported but these are not as common.
• Xcopri is a schedule 5 controlled substance (C-V) because it may be habit-forming and lead to abuse or dependence. It has a lower potential for abuse than substances scheduled in schedule 4 and schedule 3.
• Discontinuing Xcopri may lead to withdrawal symptoms such as insomnia (trouble sleeping), decreased appetite, depressed mood, tremor, and amnesia (memory loss). Discontinue it slowly over 2 weeks.
• Can cause weight loss for a small percentage of users. In clinical trials, up to 2% of patients experienced weight loss, and up to 5% of patients had decreased appetite. Most people will not see a weight change.
• The dose must be titrated up slowly, starting with 12.5mg for 2 weeks, 25mg daily for 2 weeks, 50mg daily for 2 weeks, 100mg daily for 2 weeks, 150mg daily for 2 weeks, and then 200mg thereafter as tolerated, which may be increased to 400mg once daily (the maximum dosage) if necessary for seizure control. Advise patients not to exceed this recommended titration schedule or maximum dosage because it increases the risk of serious side effects.
• The dosage needs to be reduced for liver disease (maximum 200mg once daily). Do not use in people with severe liver disease.
• Consider a dosage reduction in those with renal impairment (CLCR less than 90 ml/min). Do not use in patients with end-stage renal disease.
• Should not be used by anyone with familial Short QT syndrome or who is allergic to cenobamate or any of its inactive ingredients.
• There are reports of drug reactions with eosinophilia and systemic symptoms (DRESS) occurring in patients taking Xcopri when it was titrated rapidly (weekly or faster). This is a severe adverse drug reaction and symptoms include an extensive skin rash, visceral organ involvement, lymphadenopathy, and blood test abnormalities. If DRESS occurs then discontinue Xcopri immediately and do not restart.
• QT shortening of greater than 20 msec can occur with Xcopri and people with Familial Short QT syndrome should not be treated with Xcopri and caution should be used when administering it with other medications that also shorten the QT interval.
• Like other anticonvulsants, Xcopri can increase the risk of suicidal thoughts or behavior. Monitor patients for any worsening of depression, suicidal thoughts or behaviors, or any unusual changes in mood or behavior. Psychosis (hallucinations or delusions), hostility and aggression have also been observed in postmarketing reports.
• May also cause changes in laboratory abnormalities, such as elevations in hepatic transaminases (up to 7.6 times the upper limit of normal with 400mg Xcopri), and increased potassium levels. It may also increase the baseline incidence of appendicitis.
• Xcopri has not been studied in children and should not be used in children and adolescents under the age of 18 years.
• Caution when using in elderly people because trial data did not include many patients over the age of 65 years. Start with a low dose and titrate slowly and take into account decreased liver, kidney, cardiac, or cognitive function and the likelihood of interacting medications.
• Only use during pregnancy if the benefits outweigh the risks. Animal data show an increase in embryo mortality, reduced body weights, and increased skeletal ossification at high dosages, which also caused maternal toxicity. There was a high rate of embryofetal deaths. There is no data on the use of Xcopri during breastfeeding, but concentrations in rat milk were similar to those found in rat plasma.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• Take Xcopri at any time of the day, either with or without food.
• Swallow tablets whole with liquid. Do not crush or chew.
• The dose must be titrated up slowly. Do not exceed this recommended titration schedule or the maximum dosage because it increases the risk of serious side effects.
• Keep your medicine in a safe place away from children and pets. Xcopri is a controlled substance because it can be misused or lead to dependence.
• Xcopri may also make you feel sleepy, tired, and dizzy, affect your steadiness or impair your walking.
• The most common side effects of Xcopri in studies were somnolence (sleepiness), dizziness, fatigue, diplopia (double vision), and headache.
• Do not drink alcohol while taking this medicine or take it with other medicines that can make you sleepy or dizzy without first talking to your healthcare provider. The effects can get worse and may be unsafe. Ask your doctor before using an opioid drug, a sleeping pill, a muscle relaxer, or medicine for anxiety with this medicine.
• Xcopri can cause sedation, and memory impairment, and affect your ability to drive, operate machinery, or make important decisions. Do not drive, operate heavy machinery, or do other dangerous activities until you know how Xcopri affects you. Xcopri can also increase your risk of falls and possible fractures because it can cause vertigo, and dizziness, and impair your coordination. Get up slowly from sitting or lying down to a standing position.
• Other side effects include visual changes such as blurred vision, double vision, and impaired vision. Talk to your doctor if you experience any worrisome side effects, such as a fever or rash associated with swollen lymph nodes, heart palpitations, or suicidal thoughts, or if you are having trouble tolerating Xcopri.
• Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs. Tell your doctor if you take any other medications including over-the-counter supplements or herbal remedies. Be aware that Xcopri can decrease the effectiveness of oral contraceptives and you should use non-hormonal methods of birth control, such as condoms.
• Keep this medicine in a safe place where others, including children, family members, and pets, cannot get to it. Selling or giving away Xcopri is against the law and may harm others.
• Do not stop taking Xcopri without first talking to your healthcare provider. In addition to withdrawal symptoms, abruptly stopping treatment can lead to serious problems like seizures that will not stop (status epilepticus). When it is time to discontinue Xcopri you will need to discontinue it slowly, over at least 2 weeks.
• Tell your doctor if you become pregnant or intend to become pregnant. If you do become pregnant then you are encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (toll-free 1-888-233-2334 or visit http://www.aedpregnancyregistry.org/) which collects information about the safety of drugs during pregnancy.

• Two RCTs investigated the effectiveness of Xcopri in adults with partial-onset seizures and both studies found a significant reduction in seizure frequency. Study 1 (n=221) reported a 55.6% reduction in seizure frequency per 28 days in those assigned Xcopri 200 mg/day compared to a 21.5% reduction in seizure frequency for those assigned a placebo. Study 2 (n= 434) reported a 36.3% reduction in seizure frequency in those assigned Xcopri 100 mg/day, a 55.2% reduction in those assigned 200 mg/day, and a 55.3% reduction in those assigned 400 mg/day, compared to only a 24.3% reduction in those given a placebo. In Study 2, over 10% reported no partial seizures during treatment with Xcopri compared to just 1% assigned placebo.
• The abuse potential of Xcopri 200 mg and 400 mg doses were compared to a placebo (an inactive agent) in studies conducted on people who abused sedatives. At the 400 mg dose, subjective responses such as “Drug Liking,” “Overall Drug Liking,” “Take Drug Again,” and “Good Drug Effects” were statistically greater than the responses produced by placebo. Euphoric mood (like pleasure, excitement, and strong feelings of well-being and happiness) occurred to a greater extent with Xcopri 400 mg (8%) than with placebo (0%). In other Xcopri studies in participants with epilepsy, euphoric mood, confusion, and sleepiness occurred at low rates (0.5-2.5%).

Medicines that interact with Xcopri may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Xcopri.

More than 536 medications interact with Xcopri, and most of them are considered major or moderate interactions. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed. Common medications that may interact with Xcopri include:

• antibiotics such as clarithromycin, doxycycline, erythromycin
• anticonvulsants such as carbamazepine, lamotrigine, phenytoin, and phenobarbitone (Xcopri can either reduce the efficacy of other anticonvulsants or increase levels of other anticonvulsants - see individual interaction monographs for advice)
• antihistamines, such as azelastine, cetirizine, or levocetirizine
• antipsychotics, such as aripiprazole, clozapine, haloperidol, or quetiapine
• antivirals, such as boceprevir, darunavir, raltegravir, or elvitegravir
• cancer medications, such as acalabrutinib, or cyclophosphamide
• clobazam
• clonidine
• CNS depressants, such as benzodiazepines, opioids, sleeping medications, or sedating antihistamines
• CYP2B6 substrates such as cyclophosphamide, bupropion, ketamine, pethidine, propofol, methadone, nevirapine, and efavirenz
• CYP2C19 substrates such as omeprazole, carisprodol, or citalopram
• CYP3A4 substrates such as acetaminophen, codeine, ciclosporin, diazepam, or erythromycin.
• dextromethorphan
• heart medications, such as amiodarone, amlodipine, diltiazem, or nifedipine
• HIV medications such as indinavir and ritonavir
• medications that reduce the risk of blood clotting, such as apixaban or dabigatran
• medications that shorten the QT interval, such as digoxin and promethazine
• metoclopramide
• muscle relaxants, such as baclofen
• opioid analgesics such as buprenorphine, codeine, fentanyl, oxycodone, and morphine
• oral contraceptives (women using oral contraceptives should use additional or alternative non-hormonal forms of birth control) and hormonal treatments
• Parkinson's disease medications, such as selegiline
• tacrolimus
• tamoxifen
• tramadol
• trazodone
• valproate.

Alcohol may worsen the side effects of Xcopri such as drowsiness, dizziness, and liver toxicity.

Note that this list is not all-inclusive and includes only common medications that may interact with Xcopri. You should refer to the prescribing information for Xcopri for a complete list of interactions.