Xcopri 25mg Tablets
It is used to help control certain kinds of seizures.
Drug Class
Anticonvulsant
Pharmacologic Class
Sodium channel blocker; GABA-A receptor positive allosteric modulator
Pregnancy Category
Not available
FDA Approved
Nov 2019
DEA Schedule
Not Controlled
Overview
What is this medicine?
Xcopri (cenobamate) is a medication used to treat a specific type of seizure called focal-onset seizures in adults. It works by calming overactive nerve signals in the brain that can cause seizures.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
You can take your medication with or without food.
If you have difficulty swallowing the tablets whole, you can mix them with water. To do this, crush the required number of tablets and add them to 25 mL of water in a cup. Stir the mixture well and drink it immediately. Do not store the mixture for later use.
To make sure you take the entire dose, rinse the cup with an additional 25 mL of water and drink it. If any tablet residue remains in the cup, repeat the rinsing process.
If you have a feeding tube, you can use this medication as directed by your healthcare provider. After administering the medication, flush the feeding tube.
Continuing Your Medication
Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom.
Keep your medication in a safe and secure location, out of the reach of children and pets. Consider using a locked box or area to store your medication.
* Keep all medications away from pets.
Missing a Dose
If you forget to take a dose, make sure you know what to do. If you are unsure, contact your doctor for guidance.
To ensure you get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
You can take your medication with or without food.
If you have difficulty swallowing the tablets whole, you can mix them with water. To do this, crush the required number of tablets and add them to 25 mL of water in a cup. Stir the mixture well and drink it immediately. Do not store the mixture for later use.
To make sure you take the entire dose, rinse the cup with an additional 25 mL of water and drink it. If any tablet residue remains in the cup, repeat the rinsing process.
If you have a feeding tube, you can use this medication as directed by your healthcare provider. After administering the medication, flush the feeding tube.
Continuing Your Medication
Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom.
Keep your medication in a safe and secure location, out of the reach of children and pets. Consider using a locked box or area to store your medication.
* Keep all medications away from pets.
Missing a Dose
If you forget to take a dose, make sure you know what to do. If you are unsure, contact your doctor for guidance.
Lifestyle & Tips
- Take Xcopri exactly as prescribed, usually once a day. Do not stop taking it suddenly without talking to your doctor, as this can cause seizures to worsen.
- Follow the slow titration schedule carefully to reduce the risk of serious side effects like a severe rash (DRESS syndrome).
- Avoid or limit alcohol consumption, as it can increase side effects like dizziness and drowsiness.
- Be cautious when driving or operating machinery until you know how Xcopri affects you, as it can cause dizziness, drowsiness, and vision problems.
- If you are taking hormonal birth control, be aware that Xcopri can make it less effective. Discuss alternative or additional birth control methods with your doctor.
- Report any new or worsening symptoms of depression, unusual changes in mood or behavior, or suicidal thoughts to your doctor immediately.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 12.5 mg once daily for 2 weeks; Titration: Increase to 25 mg once daily for 2 weeks, then 50 mg once daily for 2 weeks, then 100 mg once daily for 2 weeks, then 150 mg once daily for 2 weeks, then 200 mg once daily. Maintenance: 200-400 mg once daily.
Dose Range:
12.5 - 400 mg
Condition-Specific Dosing:
Maintenance:
200-400 mg once daily, based on response and tolerability.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed.
Moderate:
No dose adjustment needed.
Severe:
Consider starting at 12.5 mg once daily and titrating to a maximum of 300 mg once daily. Monitor closely.
Dialysis:
Not studied. Use with caution; consider maximum 300 mg once daily and monitor closely.
Hepatic Impairment:
Mild:
No dose adjustment needed.
Moderate:
Consider starting at 12.5 mg once daily and titrating to a maximum of 200 mg once daily. Monitor closely.
Severe:
Not recommended due to lack of data and potential for increased exposure.
Pharmacology
Mechanism of Action
Cenobamate's precise mechanism of action is unknown, but it is thought to involve two distinct mechanisms: 1) Reduction of repetitive neuronal firing by inhibiting the persistent sodium current (INa), thereby stabilizing the inactivated state of voltage-gated sodium channels. 2) Enhancement of inhibitory synaptic currents by acting as a positive allosteric modulator of the GABA-A ion channel at a non-benzodiazepine binding site.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80%
Tmax:
1-4 hours (median 2 hours)
FoodEffect:
Food does not significantly affect the rate or extent of absorption.
Distribution:
Vd:
Approximately 40-50 L
ProteinBinding:
Approximately 60%
CnssPenetration:
Yes
Elimination:
HalfLife:
50-70 hours (mean 50-60 hours)
Clearance:
Approximately 0.9-1.2 L/h
ExcretionRoute:
Primarily renal (approximately 93% as metabolites, <1% as unchanged drug)
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Gradual, due to slow titration schedule.
PeakEffect:
Achieved after reaching stable maintenance dose (typically several weeks).
DurationOfAction:
Once daily dosing due to long half-life.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Severe dizziness or fainting
Abnormal or rapid heartbeat
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Unexplained bruising or bleeding
Severe muscle pain or weakness
Balance problems
Difficulty walking
Uncontrolled eye movements
Memory problems or loss
Confusion, difficulty focusing, or changes in behavior
Speech difficulties
Changes in vision
Like other seizure medications, this drug may increase the risk of suicidal thoughts or actions, especially in people with a history of suicidal behavior. If you experience any new or worsening symptoms, such as:
Depression
Anxiety, restlessness, or irritability
Panic attacks
Mood or behavior changes
contact your doctor immediately. If you have suicidal thoughts or actions, seek help right away.
A rare but potentially life-threatening condition has occurred in people taking seizure medications like this one. If you experience any of the following symptoms, contact your doctor immediately:
Swollen glands
Fever
Rash
Painful sores in the mouth or around the eyes
Chest pain
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine output
Signs of liver problems, such as:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. If you notice any of the following symptoms, contact your doctor if they bother you or do not go away:
Dizziness, drowsiness, fatigue, or weakness
Headache
Constipation, diarrhea, nausea, vomiting, or decreased appetite
Nose or throat irritation
* Back pain
This is not an exhaustive list of possible side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Severe dizziness or fainting
Abnormal or rapid heartbeat
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Unexplained bruising or bleeding
Severe muscle pain or weakness
Balance problems
Difficulty walking
Uncontrolled eye movements
Memory problems or loss
Confusion, difficulty focusing, or changes in behavior
Speech difficulties
Changes in vision
Like other seizure medications, this drug may increase the risk of suicidal thoughts or actions, especially in people with a history of suicidal behavior. If you experience any new or worsening symptoms, such as:
Depression
Anxiety, restlessness, or irritability
Panic attacks
Mood or behavior changes
contact your doctor immediately. If you have suicidal thoughts or actions, seek help right away.
A rare but potentially life-threatening condition has occurred in people taking seizure medications like this one. If you experience any of the following symptoms, contact your doctor immediately:
Swollen glands
Fever
Rash
Painful sores in the mouth or around the eyes
Chest pain
Signs of kidney problems, such as:
+ Inability to urinate
+ Changes in urine output
Signs of liver problems, such as:
+ Dark urine
+ Fatigue
+ Decreased appetite
+ Nausea or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Other Possible Side Effects
Most people do not experience significant side effects, but some may occur. If you notice any of the following symptoms, contact your doctor if they bother you or do not go away:
Dizziness, drowsiness, fatigue, or weakness
Headache
Constipation, diarrhea, nausea, vomiting, or decreased appetite
Nose or throat irritation
* Back pain
This is not an exhaustive list of possible side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe rash (especially if accompanied by fever, swollen lymph nodes, facial swelling, or yellowing of skin/eyes)
- Difficulty breathing or swallowing
- Swelling of the face, lips, tongue, or throat
- Unusual bruising or bleeding
- Signs of liver problems (e.g., dark urine, yellow skin/eyes, severe stomach pain, nausea/vomiting)
- Significant dizziness or drowsiness that interferes with daily activities
- Double vision or blurred vision
- Problems with coordination or balance
- New or worsening depression, anxiety, agitation, or suicidal thoughts
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Existing health conditions, specifically:
+ Kidney disease
+ Liver disease
+ Familial Short QT syndrome
Please note that this is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to discuss all of your:
Medications, including prescription and over-the-counter (OTC) drugs, as well as natural products and vitamins
Health problems
with your doctor and pharmacist. They will help determine whether it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Existing health conditions, specifically:
+ Kidney disease
+ Liver disease
+ Familial Short QT syndrome
Please note that this is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to discuss all of your:
Medications, including prescription and over-the-counter (OTC) drugs, as well as natural products and vitamins
Health problems
with your doctor and pharmacist. They will help determine whether it is safe to take this medication in conjunction with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before operating a vehicle or engaging in any activity that requires alertness and clear vision, wait until you understand how this medication affects you.
Consult your doctor before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions.
If you experience changes in your seizures or if they worsen after starting this medication, discuss this with your doctor promptly.
Do not abruptly discontinue this medication without first consulting your doctor, as this may increase your risk of seizures. If you need to stop taking this medication, your doctor will guide you on how to gradually taper off the dosage.
Be aware that this medication has the potential for abuse and dependence. Adhere strictly to your doctor's instructions for taking this medication. If you have a history of substance abuse or dependence, including alcohol or drugs, inform your doctor.
Note that birth control pills and other hormone-based contraceptives may be less effective while taking this medication. To prevent pregnancy, use an additional form of birth control, such as condoms.
If you are pregnant, planning to become pregnant, or are breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Before operating a vehicle or engaging in any activity that requires alertness and clear vision, wait until you understand how this medication affects you.
Consult your doctor before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions.
If you experience changes in your seizures or if they worsen after starting this medication, discuss this with your doctor promptly.
Do not abruptly discontinue this medication without first consulting your doctor, as this may increase your risk of seizures. If you need to stop taking this medication, your doctor will guide you on how to gradually taper off the dosage.
Be aware that this medication has the potential for abuse and dependence. Adhere strictly to your doctor's instructions for taking this medication. If you have a history of substance abuse or dependence, including alcohol or drugs, inform your doctor.
Note that birth control pills and other hormone-based contraceptives may be less effective while taking this medication. To prevent pregnancy, use an additional form of birth control, such as condoms.
If you are pregnant, planning to become pregnant, or are breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Severe drowsiness
- Dizziness
- Ataxia (lack of coordination)
- Blurred vision
- Nystagmus (involuntary eye movements)
- Coma
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Management is supportive, including close monitoring of vital signs and clinical status.
Drug Interactions
Major Interactions
- Phenytoin (cenobamate can decrease phenytoin levels)
- Carbamazepine (cenobamate can decrease carbamazepine levels)
- Lamotrigine (cenobamate can decrease lamotrigine levels)
- Oral contraceptives (cenobamate can decrease efficacy of hormonal contraceptives)
- Drugs metabolized by CYP3A4 (e.g., midazolam, simvastatin, triazolam, alprazolam, tacrolimus, cyclosporine, fentanyl, oxycodone, quetiapine, aripiprazole, some calcium channel blockers) - cenobamate can decrease their exposure.
- Drugs metabolized by CYP2B6 (e.g., bupropion, efavirenz) - cenobamate can decrease their exposure.
Moderate Interactions
- Phenobarbital (cenobamate can decrease phenobarbital levels)
- Clobazam (cenobamate can decrease clobazam levels and increase N-desmethylclobazam levels)
- Valproate (cenobamate can decrease valproate levels)
- Drugs metabolized by CYP2C19 (e.g., clopidogrel, omeprazole, diazepam) - cenobamate can increase their exposure.
Monitoring
Baseline Monitoring
ECG
Rationale: To assess for baseline cardiac rhythm and QT interval, as cenobamate can cause dose-dependent QT shortening.
Timing: Prior to initiation
Liver function tests (ALT, AST, bilirubin)
Rationale: To assess baseline hepatic function, especially given hepatic metabolism and rare risk of DRESS.
Timing: Prior to initiation
Renal function (SCr, eGFR)
Rationale: To assess baseline renal function, as dose adjustments may be needed in severe impairment.
Timing: Prior to initiation
Complete Blood Count (CBC)
Rationale: To assess for baseline hematologic parameters, though significant hematologic adverse events are rare.
Timing: Prior to initiation
Routine Monitoring
Clinical response (seizure frequency)
Frequency: Regularly during titration and maintenance
Target: Reduction in seizure frequency
Action Threshold: Lack of efficacy or worsening seizures may require dose adjustment or alternative therapy.
Adverse effects (e.g., somnolence, dizziness, fatigue, diplopia, DRESS symptoms)
Frequency: Regularly, especially during titration
Target: Tolerable side effect profile
Action Threshold: Intolerable side effects may require dose reduction, slower titration, or discontinuation. Suspect DRESS if rash with systemic symptoms.
ECG (QT interval)
Frequency: Consider at higher doses or if cardiac risk factors present
Target: Normal QT interval (corrected)
Action Threshold: Significant QT shortening (e.g., QTc <340 ms) may warrant dose reduction or discontinuation.
Drug levels of co-administered AEDs (e.g., phenytoin, lamotrigine, carbamazepine, valproate, clobazam)
Frequency: As clinically indicated, especially after dose changes of cenobamate or co-administered AEDs
Target: Therapeutic range for co-administered AEDs
Action Threshold: Subtherapeutic or supratherapeutic levels may require dose adjustment of the co-administered AED.
Symptom Monitoring
- Rash (especially if accompanied by fever, lymphadenopathy, facial swelling, eosinophilia, or liver/kidney involvement - suggestive of DRESS)
- Dizziness
- Somnolence/Sedation
- Fatigue
- Diplopia (double vision)
- Nausea/Vomiting
- Headache
- Blurred vision
- Difficulty with coordination/ataxia
- Changes in mood or behavior (e.g., depression, suicidal thoughts)
Special Patient Groups
Pregnancy
Limited human data on cenobamate use in pregnant women are insufficient to inform a drug-associated risk for major birth defects or miscarriage. In animal studies, adverse developmental effects (e.g., increased embryofetal mortality, decreased fetal body weights, skeletal variations) were observed at clinically relevant exposures. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential risk, as organogenesis occurs during this period. Animal data suggest embryofetal toxicity.
Second Trimester:
Potential risk, continued fetal development.
Third Trimester:
Potential risk, continued fetal development and potential for withdrawal symptoms in neonate if exposed late in pregnancy (though not specifically studied for cenobamate).
Lactation
Cenobamate is present in the milk of lactating rats. It is unknown whether cenobamate is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, including sedation and feeding difficulties, breastfeeding is not recommended during treatment with cenobamate.
Infant Risk:
L3 (Moderate risk) - Potential for sedation, feeding difficulties, and other adverse effects due to drug excretion into milk. Monitor infant for drowsiness, poor feeding, and developmental milestones.
Pediatric Use
Safety and effectiveness in pediatric patients (under 18 years of age) have not been established.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Clinical Information
Clinical Pearls
- Strict adherence to the slow titration schedule is crucial to minimize the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, a rare but serious hypersensitivity reaction.
- Cenobamate can cause dose-dependent QT interval shortening. While generally not clinically significant, caution is advised in patients with pre-existing cardiac conditions or those on other QT-affecting medications.
- Patients should be advised about potential CNS depressant effects (dizziness, somnolence, fatigue) and cautioned against driving or operating machinery until they know how the drug affects them.
- Cenobamate is a strong inducer of CYP3A4 and CYP2B6, and a moderate inhibitor of CYP2C19. This can significantly impact the levels of many co-administered drugs, including other AEDs and hormonal contraceptives. Careful monitoring and dose adjustments of concomitant medications are often necessary.
- Consider therapeutic drug monitoring for co-administered AEDs (e.g., phenytoin, lamotrigine, carbamazepine) when initiating or adjusting cenobamate, as their levels may decrease.
Alternative Therapies
- Levetiracetam
- Lamotrigine
- Carbamazepine
- Oxcarbazepine
- Lacosamide
- Zonisamide
- Topiramate
- Perampanel
- Brivaracetam
- Eslicarbazepine acetate
Cost & Coverage
Average Cost:
Check current per 30 tablets
Insurance Coverage:
Tier 3 or Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, it's crucial to seek immediate medical attention or contact your local poison control center. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount, and the time it occurred.
This medication is accompanied by a Medication Guide, which is a valuable resource that provides important information about your treatment. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about your medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, it's crucial to seek immediate medical attention or contact your local poison control center. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount, and the time it occurred.