Xcopri 12.5-25mg Titration Pak 28s
It is used to help control certain kinds of seizures.
Drug Class
Antiepileptic drug (AED)
Pharmacologic Class
Voltage-gated sodium channel inhibitor; GABA-A receptor positive allosteric modulator
Pregnancy Category
Not available
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 electrical signals in the brain that can cause seizures. It's important to start with a very low dose and slowly increase it over several weeks to help your body adjust and reduce the risk of side effects.
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 titration schedule carefully. Do not increase your dose faster than instructed.
- 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.
- Report any new or worsening symptoms, especially skin rash, fever, swelling, or changes in mood/behavior, to your doctor immediately.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial titration: 12.5 mg once daily for 2 weeks, then 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. Further increases to 300 mg or 400 mg once daily may be considered based on response and tolerability.
Dose Range:
200 - 400 mg
Condition-Specific Dosing:
focalOnsetSeizures:
Initial titration as above, maintenance dose typically 200-400 mg once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dosage adjustment needed.
Moderate:
Maximum recommended dose is 300 mg once daily.
Severe:
Maximum recommended dose is 300 mg once daily.
Dialysis:
No specific recommendations; cenobamate is not dialyzable. Maximum recommended dose is 300 mg once daily.
Hepatic Impairment:
Mild:
Maximum recommended dose is 200 mg once daily.
Moderate:
Maximum recommended dose is 200 mg once daily.
Severe:
Maximum recommended dose is 150 mg once daily.
Pharmacology
Mechanism of Action
Cenobamate is an antiepileptic drug that is thought to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents (preferentially the inactivated state) and to enhance GABA-A receptor activity (positive allosteric modulator at a non-benzodiazepine binding site).
Pharmacokinetics
Absorption:
Bioavailability:
Not available (well absorbed)
Tmax:
1-4 hours
FoodEffect:
Food does not affect the extent of absorption, but may delay Tmax by 1-2 hours.
Distribution:
Vd:
40-50 L
ProteinBinding:
Approximately 60%
CnssPenetration:
Yes
Elimination:
HalfLife:
50-70 hours (single dose); 60-90 hours (multiple doses)
Clearance:
Not available
ExcretionRoute:
Renal (approximately 93% as metabolites), Fecal (approximately 5%)
Unchanged:
Less than 1% in urine
Pharmacodynamics
OnsetOfAction:
Gradual (due to titration schedule)
PeakEffect:
Achieved after reaching steady-state (approximately 14 days with once-daily dosing)
DurationOfAction:
Sustained (due to long half-life, allows once-daily dosing)
Safety & Warnings
BLACK BOX WARNING
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome: Cenobamate can cause DRESS, a serious and potentially fatal hypersensitivity reaction. The incidence of DRESS is higher with rapid titration or higher initial doses. Patients should be instructed to seek immediate medical attention if they develop a rash with fever, swollen lymph nodes, or other organ involvement. Cenobamate should be immediately discontinued if DRESS is suspected.
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 medical attention immediately:
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 right away. If you have suicidal thoughts or actions, seek medical help immediately.
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 right away:
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 experience any of the following side effects and they bother you or do not go away, contact your doctor:
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 medical attention immediately:
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 right away. If you have suicidal thoughts or actions, seek medical help immediately.
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 right away:
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 experience any of the following side effects and they bother you or do not go away, contact your doctor:
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 skin rash (especially if severe, widespread, 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 dizziness or extreme drowsiness
- Changes in vision (e.g., double vision)
- New or worsening depression, anxiety, agitation, or suicidal thoughts/behavior
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.
If you have a history of 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 health conditions and medications with your doctor. Please provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
Your health problems, including any medical conditions or diseases
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety. It is vital to verify that it is safe to take this medication in combination with your other medications and health conditions.
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.
If you have a history of 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 health conditions and medications with your doctor. Please provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
Your health problems, including any medical conditions or diseases
Before starting, stopping, or changing the dose of any medication, including this one, consult with your doctor to ensure your safety. It is vital to verify that it is safe to take this medication in combination with your other medications and health conditions.
Precautions & Cautions
It is essential to inform all of 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 with 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.
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 instruct you on how to gradually taper off the dosage.
Be aware that this medication has the potential for abuse and dependence. Adhere to your doctor's instructions for taking this medication, and inform your doctor if you have a history of substance abuse or dependence on any medications or alcohol.
If you are using birth control pills or other hormone-based contraceptives, 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.
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 with 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.
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 instruct you on how to gradually taper off the dosage.
Be aware that this medication has the potential for abuse and dependence. Adhere to your doctor's instructions for taking this medication, and inform your doctor if you have a history of substance abuse or dependence on any medications or alcohol.
If you are using birth control pills or other hormone-based contraceptives, 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
- Nystagmus (involuntary eye movements)
- Coma
What to Do:
Seek immediate medical attention or call Poison Control at 1-800-222-1222. There is no specific antidote. Treatment is supportive, including monitoring vital signs and managing symptoms.
Drug Interactions
Major Interactions
- Drugs that prolong the QT interval (e.g., Class IA and III antiarrhythmics, antipsychotics, some antibiotics) - Cenobamate can cause QTc shortening, which may be problematic with drugs that prolong QTc.
- CYP2C19 substrates (e.g., clobazam, phenytoin, phenobarbital) - Cenobamate is a strong inhibitor of CYP2C19, leading to increased levels of these drugs.
- CYP3A4 substrates (e.g., midazolam, oral contraceptives) - Cenobamate is an inducer of CYP3A4, leading to decreased levels of these drugs.
- CYP2B6 substrates (e.g., bupropion, efavirenz) - Cenobamate is an inducer of CYP2B6, leading to decreased levels of these drugs.
Moderate Interactions
- Other CNS depressants (e.g., alcohol, benzodiazepines, opioids) - Increased risk of somnolence and dizziness.
- Phenytoin - Cenobamate can increase phenytoin levels; phenytoin can decrease cenobamate levels.
- Phenobarbital - Cenobamate can increase phenobarbital levels.
- Oral contraceptives - Reduced efficacy due to CYP3A4 induction.
Monitoring
Baseline Monitoring
ECG (Electrocardiogram)
Rationale: To assess baseline QTc interval, as cenobamate can cause QTc shortening. While QTc shortening is generally not associated with proarrhythmic risk, it's important to monitor, especially in patients with pre-existing cardiac conditions or on other medications affecting QTc.
Timing: Prior to initiation
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, as cenobamate is metabolized by the liver and dosage adjustments are needed in hepatic impairment.
Timing: Prior to initiation
Renal Function Tests (e.g., SCr, eGFR)
Rationale: To assess baseline renal function, as cenobamate is primarily excreted renally and dosage adjustments are needed in renal impairment.
Timing: Prior to initiation
Routine Monitoring
Seizure frequency and severity
Frequency: Regularly, at each follow-up visit
Target: Reduction in seizure activity
Action Threshold: Lack of efficacy or worsening seizures may require dose adjustment or alternative therapy.
Adverse effects (e.g., somnolence, dizziness, fatigue, diplopia)
Frequency: Regularly, especially during titration and dose increases
Target: Minimization of side effects
Action Threshold: Intolerable side effects may require dose reduction or slower titration.
Signs/symptoms of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome
Frequency: Throughout treatment, especially during the first 3 months
Target: Absence of rash, fever, lymphadenopathy, eosinophilia, or organ involvement
Action Threshold: Any suspicion of DRESS requires immediate discontinuation of cenobamate and prompt medical evaluation.
Mood and behavior changes (e.g., suicidal ideation)
Frequency: Regularly, at each follow-up visit
Target: Stable mood and absence of suicidal thoughts
Action Threshold: Emergence or worsening of depression, suicidal thoughts, or unusual behavior requires immediate evaluation.
Symptom Monitoring
- Rash (especially severe or widespread)
- 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 dizziness
- Extreme tiredness or somnolence
- Changes in vision (e.g., diplopia)
- Changes in mood or behavior, including suicidal thoughts or depression
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of cenobamate in pregnant women. Based on animal studies, cenobamate may cause fetal harm. A pregnancy exposure registry is available for women exposed to antiepileptic drugs during pregnancy (North American Antiepileptic Drug Pregnancy Registry: 1-888-233-2334).
Trimester-Specific Risks:
First Trimester:
Potential for major congenital malformations based on animal data; human data lacking.
Second Trimester:
Potential for developmental toxicity based on animal data; human data lacking.
Third Trimester:
Potential for developmental toxicity based on animal data; human data lacking.
Lactation
It is not known whether cenobamate is excreted in human milk. Cenobamate was excreted in the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants, including sedation and developmental effects, breastfeeding is not recommended during treatment with cenobamate.
Infant Risk:
High (potential for sedation, developmental effects)
Pediatric Use
Safety and effectiveness in pediatric patients (under 18 years of age) have not been established. Use is not recommended.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients and younger adults, but greater sensitivity of some older individuals cannot be ruled out. Dosage adjustments may be considered based on renal or hepatic impairment, which are more common in the elderly.
Clinical Information
Clinical Pearls
- Cenobamate has a unique dual mechanism of action, targeting both sodium channels and GABA-A receptors, which may contribute to its efficacy in refractory focal-onset seizures.
- The slow titration schedule is CRITICAL to minimize the risk of serious adverse reactions, particularly DRESS syndrome. Patients must be educated on the importance of adhering to the titration.
- Monitor for QTc shortening, especially in patients with pre-existing cardiac conditions or those on other medications that affect the QTc interval. While QTc shortening is generally not proarrhythmic, it's a unique effect of cenobamate.
- Be aware of significant drug interactions, especially with CYP2C19 substrates (e.g., clobazam, phenytoin) where dose adjustments of the co-administered drug may be necessary, and with CYP3A4/2B6 substrates (e.g., oral contraceptives) where efficacy may be reduced.
- Patients should be advised about potential CNS depressant effects (dizziness, somnolence) and cautioned about activities requiring mental alertness, especially during the initial titration phase.
Alternative Therapies
- Lacosamide (Vimpat)
- Perampanel (Fycompa)
- Brivaracetam (Briviact)
- Eslicarbazepine acetate (Aptiom)
- Carbamazepine (Tegretol)
- Oxcarbazepine (Trileptal)
- Lamotrigine (Lamictal)
- Levetiracetam (Keppra)
- Topiramate (Topamax)
- Zonisamide (Zonegran)
Cost & Coverage
Average Cost:
$1000 - $1500 per 28-day titration pack
Insurance Coverage:
Tier 2 or Tier 3 (Specialty Drug)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.