eslicarbazepine acetate 600 MG Oral Tablet [Aptiom]

INDICATIONS AND USAGE Eslicarbazepine acetate tablets are indicated for the treatment of partial-onset seizures in patients 4 years of age and older. Eslicarbazepine acetate tablets are 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 eslicarbazepine acetate tablet is 400 mg once daily. For some patients, treatment may be initiated at 800 mg once daily if the need for seizure reduction outweighs an increased risk of adverse reactions. Increase the dose in weekly increments of 400 mg to 600 mg once daily, based on clinical response and tolerability, to a recommended maintenance dosage of 800 mg to 1,600 mg once daily. ( 2.2 ) · Pediatric Patients: The recommended dosage of eslicarbazepine acetate tablets is based on body weight and is administered orally once daily. Increase the dose in weekly intervals based on clinical response and tolerability, to the recommended maintenance dosage ( 2.2 ). · Patients with Moderate or Severe Renal Impairment: Reduce dosage by 50%. ( 2.4 ) 2.1 Important Administration Instructions Instruct patients to administer eslicarbazepine acetate tablets either as whole or as crushed tablets. Instruct patients to take eslicarbazepine acetate tablets either with or without food. The eslicarbazepine acetate tablets dosing regimen depends on age, weight, and renal function. 2.2 General Dosing Recommendations Monotherapy and Adjunctive Therapy Adult Patients The recommended initial dosage of eslicarbazepine acetate tablet is 400 mg administered orally once daily. For some patients, treatment may be initiated at 800 mg once daily if the need for seizure reduction outweighs an increased risk of adverse reactions during initiation [see Adverse Reactions (6.1)]. Dosage should be increased in weekly increments of 400 mg to 600 mg, based on clinical response and tolerability, to a recommended maintenance dosage of 800 mg to 1,600 mg once daily. For patients on eslicarbazepine acetate tablets monotherapy, the 800 mg once daily maintenance dose should generally be considered in patients who are unable to tolerate a 1,200 mg daily dose. For patients on eslicarbazepine acetate tablets adjunctive therapy, the 1,600 mg daily dose should generally be considered in patients who did not achieve a satisfactory response with a 1,200 mg daily dose. Pediatric Patients (4 to 17 Years of Age) In pediatric patients 4 to 17 years of age, the recommended dosing regimen is dependent upon body weight and is administered orally once daily. The recommended initial dosage of eslicarbazepine acetate tablets is shown in Table 1. Dosage should be increased based on clinical response and tolerability, no more frequently than once per week. Titration increments should not exceed those shown in Table 1. The daily maintenance dosage should not exceed the maintenance dosage for each body weight range shown in Table 1. Table 1: Eslicarbazepine Acetate Tablets Once Daily Dosage Schedule for Pediatric Patients 4 to 17 Years of Age Body Weight Range Initial and Maximum Titration Increment Dosage (mg/day) Maintenance Dosage (mg/day) 11 to 21 kg 200 400 to 600 22 to 31 kg 300 500 to 800 32 to 38 kg 300 600 to 900 more than 38 kg 400 800 to 1,200 2.3 Dosage Modifications with Other Antiepileptic Drugs Some adverse reactions occur more frequently when patients take eslicarbazepine acetate tablets adjunctively with carbamazepine [see Warnings and Precautions (5.6)]. However, carbamazepine reduces the plasma concentration of eslicarbazepine [see Drug Interactions (7.1)]. When eslicarbazepine acetate tablets and carbamazepine are taken concomitantly, the dose of eslicarbazepine acetate tablets or carbamazepine may need to be adjusted based on efficacy and tolerability. For patients taking other enzyme-inducing AEDs (i.e., phenobarbital, phenytoin, and primidone), higher doses of eslicarbazepine acetate tablets may be needed [see Drug Interactions ( 7.1 )]. Eslicarbazepine acetate tablets should not be taken as an adjunctive therapy with oxcarbazepine. 2.4 Dosage Modifications in Patients with Renal Impairment In patients with moderate and severe renal impairment (i.e., creatinine clearance < 50 mL/min), the initial, titration, and maintenance dosages should generally be reduced by 50%. Titration and maintenance dosages may be adjusted according to clinical response [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )]. 2.5 Patients with Hepatic Impairment Dose adjustments are not required in patients with mild to moderate hepatic impairment. Use of eslicarbazepine acetate tablets in patients with severe hepatic impairment has not been studied, and use in these patients is not recommended [see Use in Specific Populations ( 8.7 ) and Clinical Pharmacology ( 12.3 )]. 2.6 Discontinuation of Eslicarbazepine Acetate Tablets When discontinuing eslicarbazepine acetate tablets, reduce the dosage gradually and avoid abrupt discontinuation in order to minimize the risk of increased seizure frequency and status epilepticus [see Warnings and Precautions ( 5.7 )].

WARNINGS AND PRECAUTIONS • Suicidal Behavior and Ideation: Monitor for suicidal thoughts or behavior. ( 5.1 ) • Serious Dermatologic Reactions, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Anaphylactic Reactions and Angioedema: Monitor and discontinue if another cause cannot be established. ( 5.2 , 5.3 , 5.4 ) • Hyponatremia: Monitor sodium levels in patients at risk or patients experiencing hyponatremia symptoms. ( 5.5 ) • Neurological Adverse Reactions: Monitor for dizziness, disturbance in gait and coordination, somnolence, fatigue, cognitive dysfunction, and visual changes. Use caution when driving or operating machinery. ( 5.6 ) • Withdrawal of eslicarbazepine acetate: Withdraw eslicarbazepine acetate gradually to minimize the risk of increased seizure frequency and status epilepticus. ( 2.6 , 5.7 , 8.1 ) • Drug Induced Liver Injury: Discontinue eslicarbazepine acetate tablets in patients with jaundice or evidence of significant liver injury. ( 5.8 ) • Hematologic Adverse Reactions: Consider discontinuing. ( 5.10 ) 5.1 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including eslicarbazepine acetate, 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. Pooled analyses of 199 placebo-controlled clinical trials (mono-and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% confidence interval [CI]: 1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number of events is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs. Table 3: Risk of Suicidal Thoughts or Behaviors by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Differences: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials in patients with epilepsy than in clinical trials in patients with psychiatric or other conditions, but the absolute risk differences were similar for epilepsy and psychiatric indications. Anyone considering prescribing eslicarbazepine acetate tablets or any other AED must balance this risk with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression; any unusual changes in mood or behavior; or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers. 5.2 Serious Dermatologic Reactions Serious dermatologic reactions including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in association with eslicarbazepine acetate use. Serious and sometimes fatal dermatologic reactions, including TEN and SJS, have also been reported in patients using oxcarbazepine or carbamazepine which are chemically related to eslicarbazepine acetate. The reporting rate of these reactions associated with oxcarbazepine use exceeds the background incidence rate estimates by a factor of 3-to 10-fold. The reporting rates for eslicarbazepine acetate have not been determined. Risk factors for the development of serious and potentially fatal dermatologic reactions with eslicarbazepine acetate use have not been identified. If a patient develops a dermatologic reaction while taking eslicarbazepine acetate tablets, discontinue eslicarbazepine acetate tablets use, unless the reaction is clearly not drug-related. Patients with a prior dermatologic reaction with oxcarbazepine, carbamazepine, or eslicarbazepine acetate should ordinarily not be treated with eslicarbazepine acetate [see Contraindications ( 4 )]. 5.3 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, has been reported in patients taking eslicarbazepine acetate tablets. DRESS may be fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Eslicarbazepine acetate tablets should be discontinued and not be resumed if an alternative etiology for the signs or symptoms cannot be established. Patients with a prior DRESS reaction with either oxcarbazepine or eslicarbazepine acetate should not be treated with eslicarbazepine acetate tablets [see Contraindications ( 4 )] . 5.4 Anaphylactic Reactions and Angioedema Rare cases of anaphylaxis and angioedema have been reported in patients taking eslicarbazepine acetate tablets. Anaphylaxis and angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with eslicarbazepine acetate, the drug should be discontinued. Patients with a prior anaphylactic-type reaction with either oxcarbazepine or eslicarbazepine acetate should not be treated with eslicarbazepine acetate [see Contraindications ( 4 )]. 5.5 Hyponatremia Clinically significant hyponatremia (sodium <125 mEq/L) can develop in patients taking eslicarbazepine acetate tablets. Measurement of serum sodium and chloride levels should b

CONTRAINDICATIONS Eslicarbazepine acetate tablets are contraindicated in patients with a hypersensitivity to eslicarbazepine acetate or oxcarbazepine [see Warnings and Precautions ( 5.2 , 5.3 , and 5.4 )] . Hypersensitivity to eslicarbazepine acetate or oxcarbazepine. ( 4 )

Mechanism of Action Eslicarbazepine acetate tablets is extensively converted to eslicarbazepine, which is considered to be responsible for therapeutic effects in humans. The precise mechanism(s) by which eslicarbazepine exerts anticonvulsant activity is unknown but is thought to involve inhibition of voltage-gated sodium channels.