Introducing
new
xcopri
® (cenobamate tablets) CV
Are you a
US healthcare professional?
safety hero

SAFETY

Most common adverse reactions
(10% for XCOPRI and greater than placebo)
1*

safety-moa-2-infographic 00 00 00 0 00 00 00 00 00 00 00 00 0 0 0 00 00 00 0 00
safety-moa-1-mobile-infographic 00 00 0 0 0 00 00 00 0 00 00 00 00 0 00 00 00 00 00 00

*Safety information is based on pooled data from Study 1 and Study 2.

  • Mood-related adverse events were not common in patients taking XCOPRI® (cenobamate tablets) CV1
  • Discontinuation rates due to adverse reactions were 11% (100 mg), 9% (200 mg), and 21% (400 mg) for patients on XCOPRI compared with 4% for placebo1

Drug reaction with eosinophilia and systemic symptom (DRESS), also known as multiorgan sensitivity, has been reported in patients taking antiepileptic drugs, including XCOPRI. DRESS has been reported, including 1 fatality, when XCOPRI is titrated rapidly (weekly or faster titration). No cases of DRESS were reported in an open-label safety study of 1339 epilepsy patients when XCOPRI was initiated at 12.5 mg/day and titrated every 2 weeks. This finding does not establish that the risk of DRESS is prevented by a slower titration; however, XCOPRI should be initiated at 12.5 mg once daily and titrated every 2 weeks.1

This is not a full list of safety information. For more information, see full Prescribing Information here.

IMPORTANT PHARMACOKINETIC DRUG-DRUG INTERACTIONS

DOSE ADJUSTMENTS MAY BE NEEDED WHEN PRESCRIBING XCOPRI CONCOMITANTLY
WITH CERTAIN MEDICATIONS1
Drug or Substrate Type
Clinical Recommendation

Phenytoin

Gradually reduce phenytoin dosage by up to 50%

Phenobarbital and clobazam

Dosage as needed

Lamotrigine and carbamazepine

Dosage if needed based on therapeutic response

CYP2B6 (eg, bupropion) and CYP3A (eg, midazolam, alprazolam2) substrates

Dosage as needed

CYP2C19 substrates (eg, omeprazole, escitalopram3)

Dosage as needed

Oral contraceptives

Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with XCOPRI.  Women should use additional
or alternative non-hormonal birth control.

Pharmacokinetic drug interactions do not necessarily translate into pharmacodynamic observations and clinical responses 4

Please see Section 7.1 of the Prescribing Information for additional details on drug-drug interactions

Drug Or Substrate Type

Phenobarbital and clobazam

Clinical Recommendation

Dosage as needed

Drug Or Substrate Type

Lamotrigine and carbamazepine

Clinical Recommendation

Dosage if needed based on therapeutic response

Drug Or Substrate Type

CYP2B6 (eg, bupropion) and CYP3A (eg, midazolam, alprazolam2) substrates

Clinical Recommendation

Dosage as needed

Drug Or Substrate Type

CYP2C19 substrates (eg, omeprazole, escitalopram3)

Clinical Recommendation

Dosage as needed

Drug Or Substrate Type

Oral contraceptives

Clinical Recommendation

Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with XCOPRI.  Women should use additional
or alternative non-hormonal birth control.

Pharmacokinetic drug interactions do not necessarily translate into pharmacodynamic observations and clinical responses 4

Please see Section 7.1 of the Prescribing Information for additional details on drug-drug interactions

New XCOPRI is thought to work via a multimodal mechanism of action1*

image

XCOPRI has been shown to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents.1

image

XCOPRI is also a positive allosteric modulator of the γ-aminobutyric acid (GABAA) ion.1

*The precise mechanism by which XCOPRI exerts its anticonvulsant activity is unknown.1

References: 1. XCOPRI [package insert]. Paramus, NJ: SK Life Science, Inc. 2. Alprazolam [package insert]. Parsippany, NJ: Actavis Pharma, Inc; 2017. 3. Escitalopram [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc; 2019. 4. Data on file. SK Life Science, Inc.

Important safety
information

Contraindications

XCOPRI® (cenobamate tablets) CV is contraindicated in any patients with known hypersensitivity to the compound... or any of the components of the drug product.

XCOPRI is contraindicated in patients with Familial Short QT syndrome.

For US Healthcare Professionals Only

Important safety information

IMPORTANT SAFETY INFORMATION and INDICATION for XCOPRI® (cenobamate tablets) CV

CONTRAINDICATIONS

XCOPRI is contraindicated in any patients with known hypersensitivity to the compound or any of the components of the drug product.

XCOPRI is contraindicated in patients with Familial Short QT syndrome.

WARNINGS AND PRECAUTIONS

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including XCOPRI. DRESS has been reported, including one fatality, when XCOPRI is titrated rapidly (weekly or faster titration). No cases of DRESS were reported in an open-label safety study of 1339 partial-onset seizure patients when XCOPRI was initiated at 12.5 mg/day and titrated every two weeks. This finding does not establish that the risk of DRESS is prevented by a slower titration; however, XCOPRI should be initiated at 12.5 mg once daily and titrated every two weeks. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement. Eosinophilia is often present. If such signs or symptoms are present, the patient should be evaluated immediately. XCOPRI should be discontinued immediately and not restarted if an alternative etiology for the signs or symptoms cannot be established.

QT Shortening: XCOPRI can cause shortening of the QT interval. Caution should be used when administering XCOPRI and other drugs that shorten the QT interval as there may be a synergistic effect on the QT interval that would increase the QT shortening risk.

Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including XCOPRI, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients, their caregivers, and/or families to be alert for these behavioral changes and report them immediately to a healthcare provider.

Neurological Adverse Reactions: XCOPRI causes dose‐dependent increases in the neurologic adverse reactions including, dizziness, diplopia, disturbance in gait and coordination, somnolence, and fatigue.

Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of XCOPRI is known.

Withdrawal of AEDs: As with all antiepileptic drugs, XCOPRI should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.

MOST COMMON ADVERSE REACTIONS

In adult adjunctive therapy placebo-controlled clinical studies, the most common adverse reactions that occurred in XCOPRI-treated patients (incidence at least 10% and greater than placebo) were somnolence, dizziness, fatigue, diplopia, headache.

DOSING CONSIDERATIONS

Dosage adjustment of XCOPRI or other concomitant medications may be necessary.

  • Consider gradually reducing phenytoin dosages by up to 50% during initial titration.
  • Consider reducing dosages of phenobarbital and clobazam as needed when used concomitantly with XCOPRI. When XCOPRI and carbamazepine or lamotrigine are taken concomitantly, consider increasing dosages as needed of carbamazepine or lamotrigine.
  • Consider increasing dosages as needed of drugs which are CYP2B6 and CYP3A substrates and decreasing dosages as needed of drugs which are CYP2C19 substrates.
  • Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with XCOPRI. Women should use additional or alternative non-hormonal birth control.

Dosage reduction of XCOPRI may be considered in patients with mild to moderate and severe renal impairment. XCOPRI use is not recommended in end-stage renal disease.

The maximum recommended daily dose is 200 mg for patients with mild or moderate hepatic impairment. XCOPRI use is not recommended in patients with severe hepatic impairment

DRUG ABUSE

XCOPRI is a Schedule V controlled substance.

INDICATION

XCOPRI is indicated for the treatment of partial-onset seizures in adult patients.

Please see full Prescribing Information.

IMPORTANT SAFETY INFORMATION and INDICATION for XCOPRI® (cenobamate tablets) CV

CONTRAINDICATIONS

XCOPRI is contraindicated in any patients with known hypersensitivity to the compound or any of the components of the drug product.

XCOPRI is contraindicated in patients with Familial Short QT syndrome.

WARNINGS AND PRECAUTIONS

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as Multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including XCOPRI. DRESS has been reported, including one fatality, when XCOPRI is titrated rapidly (weekly or faster titration). No cases of DRESS were reported in an open-label safety study of 1339 partial-onset seizure patients when XCOPRI was initiated at 12.5 mg/day and titrated every two weeks. This finding does not establish that the risk of DRESS is prevented by a slower titration; however, XCOPRI should be initiated at 12.5 mg once daily and titrated every two weeks. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement. Eosinophilia is often present. If such signs or symptoms are present, the patient should be evaluated immediately. XCOPRI should be discontinued immediately and not restarted if an alternative etiology for the signs or symptoms cannot be established.

QT Shortening: XCOPRI can cause shortening of the QT interval. Caution should be used when administering XCOPRI and other drugs that shorten the QT interval as there may be a synergistic effect on the QT interval that would increase the QT shortening risk.

Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including XCOPRI, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients, their caregivers, and/or families to be alert for these behavioral changes and report them immediately to a healthcare provider.

Neurological Adverse Reactions: XCOPRI causes dose‐dependent increases in the neurologic adverse reactions including, dizziness, diplopia, disturbance in gait and coordination, somnolence, and fatigue.

Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of XCOPRI is known.

Withdrawal of AEDs: As with all antiepileptic drugs, XCOPRI should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus. But if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.

MOST COMMON ADVERSE REACTIONS

In adult adjunctive therapy placebo-controlled clinical studies, the most common adverse reactions that occurred in XCOPRI-treated patients (incidence at least 10% and greater than placebo) were somnolence, dizziness, fatigue, diplopia, headache.

DOSING CONSIDERATIONS

Dosage adjustment of XCOPRI or other concomitant medications may be necessary.

  • Consider gradually reducing phenytoin dosages by up to 50% during initial titration.
  • Consider reducing dosages of phenobarbital and clobazam as needed when used concomitantly with XCOPRI. When XCOPRI and carbamazepine or lamotrigine are taken concomitantly, consider increasing dosages as needed of carbamazepine or lamotrigine.
  • Consider increasing dosages as needed of drugs which are CYP2B6 and CYP3A substrates and decreasing dosages as needed of drugs which are CYP2C19 substrates.
  • Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with XCOPRI. Women should use additional or alternative non-hormonal birth control.

Dosage reduction of XCOPRI may be considered in patients with mild to moderate and severe renal impairment. XCOPRI use is not recommended in end-stage renal disease.

The maximum recommended daily dose is 200 mg for patients with mild or moderate hepatic impairment. XCOPRI use is not recommended in patients with severe hepatic impairment

DRUG ABUSE

XCOPRI is a Schedule V controlled substance.

INDICATION

XCOPRI is indicated for the treatment of partial-onset seizures in adult patients.

Please see full Prescribing Information.

For US Healthcare Professionals Only