HIGHLIGHTS OF PRESCRIBING INFORMATION - Aptiom

1 FULL PRESCRIBING INFORMATION :CONTENTS*1 INDICATIONS AND USAGE2 DOSAGE AND Important Administration General Dosing Dosage Modifications with OtherAntiepileptic Dosage Modifications in Patients withRenal Patients with Hepatic Discontinuation of APTIOM3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND Suicidal Behavior and Serious Dermatologic Drug Reaction with Eosinophiliaand Systemic Symptoms(DRESS)/Multiorgan Anaphylactic Reactions and Neurological Adverse Withdrawal of Drug Induced Liver Abnormal Thyroid Function Hematologic Adverse Reactions6 ADVERSE Clinical Trials Postmarketing Experience7 DRUG Other Antiepileptic Drugs CYP2C19 Substrates CYP3A4 Substrates Oral Contraceptives8 USE IN SPECIFIC Females and Males ofReproductive Pediatric Geriatric Patients with Renal Patients with Hepatic Impairment9 DRUG ABUSE AND Controlled Signs, Symptoms, and LaboratoryFindings of Acute Overdose in Treatment or Management of Overdose11 DESCRIPTION12 CLINICAL Mechanism of Pharmacokinetics13 NONCLINICAL Carcinogenesis, Mutagenesis.

2 Impairment of Fertility14 CLINICAL Monotherapy for Partial-Onset Adjunctive Therapy forPartial-Onset Seizures15 REFERENCES16 HOW SUPPLIED/STORAGE AND How Storage and Handling17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the fullprescribing INFORMATION are not OF PRESCRIBING INFORMATIONT hese HIGHLIGHTS do not include all the INFORMATION needed to useAPTIOM safely and effectively. See full PRESCRIBING informationfor (eslicarbazepine acetate) tablets, for oral useInitial Approval: 2013 RECENT MAJOR CHANGES Indications and Usage (1) 9/2017 Dosage and Administration (2) 9/2017 Warnings and Precautions (5) 9/2017 INDICATIONS AND USAGE Aptiom is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. (1)DOSAGE AND ADMINISTRATION Adult Patients: The recommended initial dosage of Aptiom is 400 mgonce daily.

3 For some patients, treatment may be initiated at 800 mg oncedaily if the need for seizure reduction outweighs an increased risk ofadverse reactions. Increase the dose in weekly increments of 400 mg to600 mg once daily, based on clinical response and tolerability, to arecommended maintenance dosage of 800 mg to 1600 mg once daily. ( ) Pediatric Patients: The recommended dosage of Aptiom is based onbody weight and is administered orally once daily. Increase the dose inweekly intervals based on clinical response and tolerability, to therecommended maintenance dosage. ( ) Patients with Moderate or Severe Renal Impairment: Reduce dosageby 50%. ( )DOSAGE FORMS AND STRENGTHS Tablets: 200 mg, 400 mg, 600 mg, 800 mg (3)CONTRAINDICATIONS Hypersensitivity to eslicarbazepine acetate or oxcarbazepine. (4)WARNINGS AND PRECAUTIONS Suicidal Behavior and Ideation: Monitor for suicidal thoughts orbehavior.

4 ( ) Serious Dermatologic Reactions, Drug Reaction with Eosinophilia andSystemic Symptoms (DRESS), Anaphylactic Reactions and Angioedema:Monitor and discontinue if another cause cannot be established. ( , , ) Hyponatremia: Monitor sodium levels in patients at risk or patientsexperiencing hyponatremia symptoms. ( ) Neurological Adverse Reactions: Monitor for dizziness, disturbance ingait and coordination, somnolence, fatigue, cognitive dysfunction, andvisual changes. Use caution when driving or operating machinery. ( ) Withdrawal of Aptiom : Withdraw Aptiom gradually to minimize the riskof increased seizure frequency and status epilepticus. ( , , ) Drug Induced Liver Injury: Discontinue Aptiom in patients with jaundiceor evidence of significant liver injury. ( ) Hematologic Adverse Reactions: Consider discontinuing.

5 ( )ADVERSE REACTIONS Most common adverse reactions in adult patients receiving Aptiom ( 4% and 2% greater than placebo): dizziness, somnolence, nausea,headache, diplopia, vomiting, fatigue, vertigo, ataxia, blurred vision,and tremor. ( ) Adverse reactions in pediatric patients are similar to those seen inadult patients. To report SUSPECTED ADVERSE REACTIONS, contact Sunovion at1-877-737-7226 or FDA at 1-800-FDA-1088 or INTERACTIONS Carbamazepine: May need dose adjustment for Aptiom orcarbamazepine. ( , , ) Phenytoin: Higher dosage of Aptiom may be necessary and doseadjustment may be needed for phenytoin. ( , , ) Phenobarbital or Primidone: Higher dosage of Aptiom may benecessary. ( , ) Hormonal Contraceptives: Aptiom may decrease the effectiveness ofhormonal contraceptives. ( , )USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm.

6 ( )See 17 for PATIENT COUNSELING INFORMATION andMedication : 10/2017 FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGEAPTIOM is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. 2 DOSAGE AND Administration InstructionsInstruct patients to administer Aptiom either as whole or as crushedtablets. Instruct patients to take Aptiom either with or without food. TheAPTIOM dosing regimen depends on age, weight, and renal Dosing RecommendationsMonotherapy and Adjunctive TherapyAdult Patients The recommended initial dosage of Aptiom is 400 mg administered orallyonce daily. For some patients, treatment may be initiated at 800 mg oncedaily if the need for seizure reduction outweighs an increased risk of adversereactions during initiation[see Adverse Reactions ( )].Dosage should beincreased in weekly increments of 400 mg to 600 mg, based on clinicalresponse and tolerability, to a recommended maintenance dosage of 800 mgto 1600 mg once daily.

7 For patients on Aptiom monotherapy, the 800 mgonce daily maintenance dose should generally be considered in patientswho are unable to tolerate a 1200 mg daily dose. For patients on Aptiom adjunctive therapy, the 1600 mg daily dose should generally be consideredin patients who did not achieve a satisfactory response with a 1200 mg daily Patients (4 to 17 Years of Age)In pediatric patients 4 to 17 years of age, the recommended dosing regimenis dependent upon body weight and is administered orally once daily. Therecommended initial dosage of Aptiom is shown in Table 1. Dosage shouldbe increased based on clinical response and tolerability, no more frequentlythan once per week. Titration increments should not exceed those shown inTable 1. The daily maintenance dosage should not exceed the maintenancedosage for each body weight range shown in Table Modifications with Other Antiepileptic DrugsSome adverse reactions occur more frequently when patients take Aptiom adjunctively with carbamazepine [see Warnings and Precautions ( )].

8 However, carbamazepine reduces the plasma concentration ofeslicarbazepine [see Drug Interactions ( )].When Aptiom andcarbamazepine are taken concomitantly, the dose of Aptiom orcarbamazepine may need to be adjusted based on efficacy and patients taking other enzyme-inducing AEDs ( , phenobarbital,phenytoin, and primidone), higher doses of Aptiom may be needed[see Drug Interactions ( )]. Aptiom should not be taken as an adjunctive therapy with oxcarbazepine. Modifications in Patients with Renal ImpairmentIn patients with moderate and severe renal impairment ( , creatinineclearance < 50 mL/min), the initial, titration, and maintenance dosagesshould generally be reduced by 50%. Titration and maintenance dosagesmay be adjusted according to clinical response [see Use in SpecificPopulations ( ) and Clinical Pharmacology ( )].

9 With Hepatic ImpairmentDose adjustments are not required in patients with mild to moderate hepaticimpairment. Use of Aptiom in patients with severe hepatic impairment hasnot been studied, and use in these patients is not recommended [see Use inSpecific Populations ( ) and Clinical Pharmacology ( )].Table 1: Aptiom Once Daily Dosage Schedulefor Pediatric Patients 4 to 17 Years of AgeBody Weight Initial and Maximum Maintenance RangeTitration IncrementDosage Dosage (mg/day)(mg/day) 11 to 21 kg200400 to 60022 to 31 kg300500 to 80032 to 38 kg300600 to 900more than 38 kg400800 to of APTIOMWhen discontinuing Aptiom , reduce the dosage gradually and avoid abruptdiscontinuation in order to minimize the risk of increased seizure frequencyand status epilepticus [see Warnings and Precautions ( )].3 DOSAGE FORMS AND STRENGTHSAPTIOM tablets are available in the following shapes and color (Table 2) withrespective one-sided engraving:4 CONTRAINDICATIONSAPTIOM is contraindicated in patients with a hypersensitivity toeslicarbazepine acetate or oxcarbazepine [see Warnings and Precautions( , , and )].

10 5 WARNINGS AND Behavior and IdeationAntiepileptic drugs (AEDs), including Aptiom , increase the risk of suicidalthoughts or behavior in patients taking these drugs for any treated with any AED for any indication should be monitored for theemergence or worsening of depression, suicidal thoughts or behavior,and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- andadjunctive therapy) of 11 different AEDs showed that patients randomized toone of the AEDs had approximately twice the risk (adjusted Relative , 95% confidence interval [CI]: , ) of suicidal thinking or behaviorcompared to patients randomized to placebo. In these trials, which had amedian treatment duration of 12 weeks, the estimated incidence of suicidalbehavior or ideation among 27,863 AED-treated patients was ,compared to among 16,029 placebo-treated patients, representingan increase of approximately one case of suicidal thinking or behavior forevery 530 patients treated.