XCOPRI

1 Dosing Considerations • XCOPRI may be taken at any time with or without food. Swallow tablets whole with liquid. Do not split, crush or chew. • XCOPRI is administered orally once daily. • Usual maintenance dose is 200 mg once daily. • Maximum daily dose is 400 mg, if needed, based on clinical response and tolerability.

This dose was associated with a higher frequency of severe adverse events and discontinuations due to adverse events during the controlled clinical trials (see 8 ADVERSE REACTIONS). Doses greater than 400 mg may lead to QT shortening greater than 20 msec (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).

• Maximum recommended dose in patients with mild or moderate hepatic impairment is 200 mg once daily, or lower, as required. 3 Pharmacokinetics, Special Populations and Conditions, Hepatic Insufficiency). • Maximum recommended dose in patients with mild, moderate, or severe renal impairment is 200 mg once daily.

Avoid use in patients with end-stage renal disease or on dialysis. • It is recommended that discontinuation of cenobamate be undertaken gradually over a period of at least 2 weeks (if possible) to minimize the potential for rebound seizures, unless safety concerns require abrupt withdrawal (see 7 WARNINGS AND PRECAUTIONS, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity).

2 Recommended Dose and Dosage Adjustment Recommended Dose The recommended initial dose and subsequent titration to target maintenance dose should not be exceeded because of the potential for serious adverse reactions (Table 1; see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX).

5 mg once daily Titration Regimen Week 3 and 4 25 mg once daily Week 5 and 6 50 mg once daily Week 7 and 8 100 mg once daily Week 9 and 10 150 mg once daily Maintenance Dose Week 11 and thereafter 200 mg once daily XCOPRI (cenobamate tablets) Page 6 of 39 If needed based on clinical response and tolerability, dose may be increased above 200 mg by increments of 50 mg once daily every two weeks to a maximum daily dose of 400 mg.

In controlled clinical trials, 400 mg/day was associated with a higher frequency of adverse events. 2 Clinical Trials Adverse Reactions).

Dosage Adjustment Pediatrics (<18 years of age):

). Doses greater than 400 mg may lead to QT shortening greater than 20 msec (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular). • Maximum recommended dose in patients with mild or moderate hepatic impairment is 200 mg once daily, or lower, as required.

3 Pharmacokinetics, Special Populations and Conditions, Hepatic Insufficiency). • Maximum recommended dose in patients with mild, moderate, or severe renal impairment is 200 mg once daily. Avoid use in patients with end-stage renal disease or on dialysis.

• It is recommended that discontinuation of cenobamate be undertaken gradually over a period of at least 2 weeks (if possible) to minimize the potential for rebound seizures, unless safety concerns require abrupt withdrawal (see 7 WARNINGS AND PRECAUTIONS, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity).

2 Recommended Dose and Dosage Adjustment Recommended Dose The recommended initial dose and subsequent titration to target maintenance dose should not be exceeded because of the potential for serious adverse reactions (Table 1; see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX).

5 mg once daily Titration Regimen Week 3 and 4 25 mg once daily Week 5 and 6 50 mg once daily Week 7 and 8 100 mg once daily Week 9 and 10 150 mg once daily Maintenance Dose Week 11 and thereafter 200 mg once daily XCOPRI (cenobamate tablets) Page 6 of 39 If needed based on clinical response and tolerability, dose may be increased above 200 mg by increments of 50 mg once daily every two weeks to a maximum daily dose of 400 mg.

In controlled clinical trials, 400 mg/day was associated with a higher frequency of adverse events. 2 Clinical Trials Adverse Reactions).

Dosage Adjustment Pediatrics (<18 years of age):

The safety and efficacy of XCOPRI in pediatric patients have not been studied. Health Canada has not authorized an indication for pediatric use.

, Hepatic/Biliary/Pancreatic 05/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR CHANGES ......................................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ......................................................................

4 1 INDICATIONS ............................................................................................................... 4 2 CONTRAINDICATIONS .................................................................................................

4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 4 4 DOSAGE AND ADMINISTRATION ................................................................................. 6 5 OVERDOSAGE..............................................................................................................

7 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 7 7 WARNINGS AND PRECAUTIONS .................................................................................. 14 8 ADVERSE REACTIONS ................................................................................................

18 9 DRUG INTERACTIONS ................................................................................................ 22 10 CLINICAL PHARMACOLOGY .......................................................................................

23 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 24 12 SPECIAL HANDLING INSTRUCTIONS ........................................................................... 25 PART II: SCIENTIFIC INFORMATION .......................................................................................

XCOPRI is contraindicated in patients: • who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

• with Familial Short QT syndrome, a family history of the syndrome, presence or history of short QT interval (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).