Xcopri 150-200mg Maintenance Pak 56
It is used to help control certain kinds of seizures.
Drug Class
Anticonvulsant
Pharmacologic Class
Voltage-gated sodium channel blocker; GABA-A receptor positive allosteric modulator
Pregnancy Category
Category C
FDA Approved
Nov 2019
DEA Schedule
Schedule V
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
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, 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 for your dose 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 ensure 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 instructed by your healthcare provider. After administering the medication through the feeding tube, flush the tube to ensure the full dose is delivered.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start feeling better.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep it in a secure location where children cannot see or access it, and where others cannot reach it. Consider using a locked box or area to store your medication. Keep all medications out of reach of pets.
Missing a Dose
If you forget to take a dose, be sure to follow the instructions provided by your doctor or healthcare provider. If you are unsure what to do, contact your doctor for guidance.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, 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 for your dose 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 ensure 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 instructed by your healthcare provider. After administering the medication through the feeding tube, flush the tube to ensure the full dose is delivered.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start feeling better.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep it in a secure location where children cannot see or access it, and where others cannot reach it. Consider using a locked box or area to store your medication. Keep all medications out of reach of pets.
Missing a Dose
If you forget to take a dose, be sure to follow the instructions provided by your doctor or healthcare provider. If you are unsure what to do, contact your doctor for guidance.
Lifestyle & Tips
- Take Xcopri exactly as prescribed by your doctor, usually once a day. Do not stop taking it suddenly, as this can cause seizures to worsen.
- It is very important to follow the slow titration schedule provided by your doctor to reduce the risk of a serious skin reaction called DRESS syndrome.
- Avoid driving or operating heavy machinery until you know how Xcopri affects you, as it can cause dizziness, drowsiness, and vision problems.
- Avoid or limit alcohol consumption, as it can increase side effects like drowsiness and dizziness.
- If you are a woman of childbearing potential, discuss effective birth control methods with your doctor, as Xcopri can make hormonal contraceptives less effective.
- Report any new or worsening symptoms, especially skin rash, fever, swollen glands, or yellowing of the skin/eyes, to your doctor immediately.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
200 mg once daily (maintenance dose)
Dose Range:
200 - 400 mg
Condition-Specific Dosing:
Maintenance Pak:
The 150-200mg Maintenance Pak is typically used after initial titration to reach the 200mg maintenance dose, or for patients who tolerate 150mg but need to titrate to 200mg. The recommended maintenance dose range is 200-400 mg/day, with some patients benefiting from up to 400 mg/day.
Titration:
Initial dose is 12.5 mg once daily, titrated gradually over several weeks to minimize risk of DRESS syndrome and other adverse effects. Titration schedule: 12.5 mg/day (weeks 1-2), 25 mg/day (weeks 3-4), 50 mg/day (weeks 5-6), 100 mg/day (weeks 7-8), 150 mg/day (weeks 9-10), 200 mg/day (week 11 onwards). Further titration to 400 mg/day may be considered based on clinical response and tolerability.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (Safety and effectiveness not established in pediatric patients <18 years of age)
Dose Adjustments
Renal Impairment:
Mild:
No dosage adjustment needed.
Moderate:
No dosage adjustment needed.
Severe:
Maximum recommended dose is 300 mg/day. Start with 12.5 mg once daily and titrate slowly.
Dialysis:
Maximum recommended dose is 300 mg/day. Cenobamate is not dialyzable. Administer after dialysis on dialysis days.
Hepatic Impairment:
Mild:
No dosage adjustment needed.
Moderate:
Maximum recommended dose is 200 mg/day. Start with 12.5 mg once daily and titrate slowly.
Severe:
Maximum recommended dose is 150 mg/day. Start with 12.5 mg once daily and titrate slowly.
Pharmacology
Mechanism of Action
Cenobamate is an anticonvulsant with a dual mechanism of action. It reduces repetitive neuronal firing by enhancing the inactivated state of voltage-gated sodium channels. It also acts as a positive allosteric modulator of the GABA-A ion channel, binding to a non-benzodiazepine site. These actions are thought to stabilize neuronal membranes and inhibit excitatory neurotransmission, thereby reducing seizure susceptibility.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 80%
Tmax:
1 to 4 hours (median 2 hours)
FoodEffect:
Food does not affect the extent of absorption, but may delay Tmax by 1-2 hours. Can be taken with or without food.
Distribution:
Vd:
Approximately 40 L
ProteinBinding:
Approximately 60%
CnssPenetration:
Yes
Elimination:
HalfLife:
50 to 70 hours (mean 60 hours)
Clearance:
Approximately 1.5 L/h
ExcretionRoute:
Primarily renal (approximately 93% as metabolites, <1% as unchanged drug)
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Not precisely defined for seizure control, but steady-state concentrations are reached in 14-21 days with once-daily dosing.
PeakEffect:
Not precisely defined for seizure control.
DurationOfAction:
Due to long half-life, once-daily dosing provides sustained therapeutic levels.
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, particularly 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 been reported 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 taking this medication do not experience significant side effects, but some may occur. If you experience any of the following side effects, 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 about side effects, 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, particularly 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 been reported 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 taking this medication do not experience significant side effects, but some may occur. If you experience any of the following side effects, 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 about side effects, 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:
- New or worsening rash (especially if widespread, blistering, or accompanied by fever)
- Fever
- Swollen lymph nodes
- Swelling of the face, eyes, lips, or tongue
- Difficulty breathing or swallowing
- Yellowing of the skin or eyes (jaundice)
- Dark urine
- Unusual bruising or bleeding
- Severe fatigue or weakness
- Muscle pain or weakness
- Severe dizziness or drowsiness
- Double vision or blurred vision
- Changes in mood or behavior (e.g., depression, anxiety, agitation, 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 symptoms you experienced.
Existing health conditions, including kidney disease or liver disease.
* If you have been diagnosed with Familial Short QT syndrome.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication in combination with your other treatments and health conditions.
Remember, do not start, stop, or adjust the dosage of any medication without first consulting your doctor to ensure your safety.
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 symptoms you experienced.
Existing health conditions, including kidney disease or liver disease.
* If you have been diagnosed with Familial Short QT syndrome.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication in combination with your other treatments and health conditions.
Remember, do not start, stop, or adjust the dosage of any medication without first consulting your doctor to ensure your safety.
Precautions & Cautions
It is essential to inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, be cautious and avoid driving or engaging in activities that require alertness and clear vision until you understand how it affects you.
Before consuming alcohol, using marijuana or other forms of cannabis, or taking prescription or over-the-counter (OTC) drugs that may impair your reactions, consult with your doctor.
If you experience changes in your seizures or if they worsen after initiating this medication, promptly discuss this with your doctor.
Do not abruptly stop taking this medication without first consulting your doctor, as this may increase your risk of seizures. If you need to discontinue 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 or dependence. Adhere strictly to your doctor's instructions for taking this medication, and inform your doctor if you have a history of substance abuse or dependence on drugs or alcohol.
If you are using birth control pills or other hormone-based birth control methods, note that this medication may reduce their effectiveness in preventing pregnancy. Consider using an additional form of birth control, such as condoms, while taking this medication.
If you are pregnant, planning to become pregnant, or are breastfeeding, consult with your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
When starting this medication, be cautious and avoid driving or engaging in activities that require alertness and clear vision until you understand how it affects you.
Before consuming alcohol, using marijuana or other forms of cannabis, or taking prescription or over-the-counter (OTC) drugs that may impair your reactions, consult with your doctor.
If you experience changes in your seizures or if they worsen after initiating this medication, promptly discuss this with your doctor.
Do not abruptly stop taking this medication without first consulting your doctor, as this may increase your risk of seizures. If you need to discontinue 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 or dependence. Adhere strictly to your doctor's instructions for taking this medication, and inform your doctor if you have a history of substance abuse or dependence on drugs or alcohol.
If you are using birth control pills or other hormone-based birth control methods, note that this medication may reduce their effectiveness in preventing pregnancy. Consider using an additional form of birth control, such as condoms, while taking this medication.
If you are pregnant, planning to become pregnant, or are breastfeeding, consult with 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 (loss of coordination)
- Blurred vision
- Nausea
- Vomiting
- Coma
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. There is no specific antidote; treatment is supportive.
Drug Interactions
Major Interactions
- Phenytoin (Cenobamate significantly decreases phenytoin levels; consider reducing phenytoin dose by 50% or more)
- Phenobarbital (Cenobamate significantly decreases phenobarbital levels; consider reducing phenobarbital dose by 50% or more)
- Carbamazepine (Cenobamate decreases carbamazepine levels; consider dose adjustment)
- Lamotrigine (Cenobamate decreases lamotrigine levels; consider dose adjustment)
- Oral Contraceptives (Cenobamate may decrease efficacy of hormonal contraceptives; advise alternative or additional birth control methods)
- Drugs metabolized by CYP3A4 (e.g., midazolam, triazolam, alprazolam, simvastatin, atorvastatin, tacrolimus, cyclosporine, sildenafil) - Cenobamate is a moderate inducer of CYP3A4, potentially reducing levels of co-administered drugs.
- Drugs metabolized by CYP2B6 (e.g., bupropion, efavirenz) - Cenobamate is a moderate inducer of CYP2B6, potentially reducing levels of co-administered drugs.
Moderate Interactions
- Clobazam (Cenobamate increases clobazam and N-desmethylclobazam levels; consider reducing clobazam dose)
- Valproate (Cenobamate may decrease valproate levels; monitor and adjust as needed)
- Topiramate (Cenobamate may decrease topiramate levels; monitor and adjust as needed)
- Drugs metabolized by CYP2C19 (e.g., clopidogrel, omeprazole, diazepam) - Cenobamate is a weak inhibitor of CYP2C19, potentially increasing levels of co-administered drugs.
Minor Interactions
- Alcohol and other CNS depressants (additive CNS depression)
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess for baseline QT interval, as cenobamate can cause QT shortening.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, especially given hepatic metabolism and potential for DRESS syndrome.
Timing: Prior to initiation of therapy.
Renal Function Tests (e.g., creatinine, eGFR)
Rationale: To assess baseline renal function, as dosage adjustments are needed in severe renal impairment.
Timing: Prior to initiation of therapy.
Complete Blood Count (CBC)
Rationale: To assess baseline hematologic status, though not a primary concern, good practice for AEDs.
Timing: Prior to initiation of therapy.
Routine Monitoring
Clinical monitoring for DRESS syndrome
Frequency: Throughout titration and early maintenance, especially during the first 3 months.
Target: Absence of rash, fever, lymphadenopathy, eosinophilia, or organ involvement.
Action Threshold: Discontinue cenobamate immediately if DRESS is suspected.
Clinical monitoring for CNS adverse effects (somnolence, dizziness, fatigue, diplopia)
Frequency: Regularly, especially during titration and dose adjustments.
Target: Tolerable levels of side effects.
Action Threshold: Consider dose reduction or slower titration if severe or intolerable.
Seizure frequency and severity
Frequency: Regularly, at each follow-up visit.
Target: Reduction in seizure frequency and/or severity.
Action Threshold: Consider dose adjustment or alternative therapy if inadequate seizure control.
Drug levels of co-administered AEDs (e.g., phenytoin, phenobarbital, carbamazepine, lamotrigine, clobazam)
Frequency: As clinically indicated, especially after cenobamate initiation or dose changes.
Target: Therapeutic range for co-administered AEDs.
Action Threshold: Adjust co-administered AED dose based on levels and clinical response.
Symptom Monitoring
- Rash (especially widespread, blistering, or associated with fever)
- Fever
- Swollen lymph nodes
- Swelling of face, eyes, lips, or tongue
- Difficulty breathing or swallowing
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Unusual bruising or bleeding
- Severe fatigue
- Muscle weakness or pain
- Dizziness
- Somnolence (excessive sleepiness)
- Fatigue
- Diplopia (double vision)
- Blurred vision
- Headache
- Nausea
- Vomiting
- Changes in mood or behavior (e.g., agitation, aggression, depression, suicidal thoughts)
Special Patient Groups
Pregnancy
Category C. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Advise women of childbearing potential to use effective contraception.
Trimester-Specific Risks:
First Trimester:
Potential for increased risk of major congenital malformations with antiepileptic drugs in general. Data specific to cenobamate are limited.
Second Trimester:
Limited data.
Third Trimester:
Limited data.
Lactation
L3 (Moderately Safe). It is unknown if cenobamate is excreted in human milk. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for cenobamate and any potential adverse effects on the breastfed infant from cenobamate or from the underlying maternal condition. Monitor breastfed infants for somnolence and feeding difficulties.
Infant Risk:
Potential for somnolence, feeding difficulties, or other adverse effects due to drug excretion in breast milk. Risk is considered moderate.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients under 18 years of age.
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
- The most critical aspect of cenobamate therapy is the slow, gradual titration to minimize the risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. Patients must be educated on the importance of adherence to the titration schedule.
- Cenobamate has a unique dual mechanism of action, making it effective for focal-onset seizures, including those refractory to other AEDs.
- Significant drug-drug interactions exist, particularly with other AEDs (phenytoin, phenobarbital, carbamazepine, lamotrigine) and hormonal contraceptives. Careful monitoring and dose adjustments of co-administered drugs are often necessary.
- Patients should be monitored for CNS side effects (dizziness, somnolence, fatigue, diplopia), especially during titration. These are generally dose-related.
- While not a Black Box Warning, DRESS syndrome is a severe, potentially life-threatening hypersensitivity reaction. Patients should be instructed to seek immediate medical attention if they develop a rash with fever, swollen lymph nodes, or other systemic symptoms.
- Cenobamate can cause QT interval shortening. While generally not clinically significant, it's a unique effect among AEDs and baseline ECG is recommended.
Alternative Therapies
- Lacosamide
- Levetiracetam
- Carbamazepine
- Oxcarbazepine
- Lamotrigine
- Topiramate
- Zonisamide
- Perampanel
- Eslicarbazepine acetate
- Brivaracetam
Cost & Coverage
Average Cost:
Not available (varies significantly by pharmacy, dosage, and region) per 30 tablets
Insurance Coverage:
Tier 3 or 4 (Specialty drug, often requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, contact your doctor immediately. It is essential to use your prescribed medication responsibly: do not share it with others, and never take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information. Please read this guide carefully and review it each time you refill your prescription. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or healthcare provider. In the event of a suspected overdose, promptly call the poison control center or seek immediate medical attention. Be prepared to provide details about the overdose, including the substance taken, the amount, and the time it occurred.