Eslicarbazepine acetate
Tablet · Oral
Uses
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 tablets 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 1600 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 tablets 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 1600 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 1200 mg daily dose. For patients on eslicarbazepine acetate tablets adjunctive therapy, the 1600 mg daily dose should generally be considered in patients who did not achieve a satisfactory response with a 1200 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 1200 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) ].
Dosage forms and strengths
Eslicarbazepine acetate tablets are available in the following shapes and color (Table 2) with respective two-sided debossing: Table 2: Eslicarbazepine Acetate Tablet Presentations Tablet Strength Tablet Color/Shape Tablet Markings Functional Score 200 mg White to off-white oblong bi-convex ‘E’ on the left side and ‘T’ on the right side of score line on one side and ‘200’ on the other side Yes 400 mg White to off-white round bi-convex ‘ET’ on one side and ‘400’ on the other side No 600 mg White to off-white oblong bi-convex ‘E’ on the left side and ‘T’ on the right side of score line on one side and ‘600’ on the other side Yes 800 mg White to off-white oblong bi-convex ‘E’ on the left side and ‘T’ on the right side of score line on one side and ‘800’ on the other side Yes Tablets: 200 mg, 400 mg, 600 mg, 800 mg ( 3 )
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 )
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 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 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Differences: Additional Drug Patients with Events Per 1000 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 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, discontinue eslicarbazepine acetate 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) ].
Side effects
The following adverse reactions are described in more detail in the Warnings and Precautions section of the label: Suicidal Behavior and Ideation [see Warnings and Precautions (5.1) ] Serious Dermatologic Reactions [see Warnings and Precautions (5.2) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.3) ] Anaphylactic Reactions and Angioedema [see Warnings and Precautions (5.4) ] Hyponatremia [see Warnings and Precautions (5.5) ] Neurological Adverse Reactions [see Warnings and Precautions (5.6) ] Drug Induced Liver Injury [see Warnings and Precautions (5.8) ] Abnormal Thyroid Function Tests [see Warnings and Precautions (5.9) ] Pancytopenia, Agranulocytosis, and Leukopenia [see Warnings and Precautions (5.10) ] Most common adverse reactions in adult patients receiving eslicarbazepine acetate (≥4% and ≥2% greater than placebo): dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, blurred vision, and tremor. ( 6.1 ) Adverse reactions in pediatric patients are similar to those seen in adult patients. To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Patients In monotherapy trials in patients with partial-onset seizures [Study 1 and Study 2, see Clinical Studies (14.1) ] , 365 patients received eslicarbazepine acetate, of whom 225 were treated for longer than 12 months and 134 for longer than 24 months. Of the patients in those trials, 95% were between 18 and 65 years old; 48% were male, and 84% were Caucasian. Across controlled and uncontrolled trials in patients receiving adjunctive therapy for partial-onset seizures, 1195 patients received eslicarbazepine acetate, of whom 586 were treated for longer than 6 months and 462 for longer than 12 months. In the placebo controlled adjunctive therapy trials in patients with partial-onset seizures (Study 3, Study 4 and Study 5), 1021 patients received eslicarbazepine acetate. Of the patients in those trials, approximately 95% were between 18 and 60 years old, approximately 50% were male, and approximately 80% were Caucasian. Monotherapy Historical Control Trials In the monotherapy epilepsy trials (Study 1 and Study 2), 13% of patients randomized to receive eslicarbazepine acetate at the recommended doses of 1200 mg and 1600 mg once daily discontinued from the trials as a result of an adverse event. The adverse reaction most commonly (≥1% on eslicarbazepine acetate) leading to discontinuation was hyponatremia. Adverse reactions observed in these studies were generally similar to those observed and attributed to drug in adjunctive placebo-controlled studies. Because these studies did not include a placebo control group, causality could not be established. Dizziness, nausea, somnolence, and fatigue were all reported at lower incidences during the AED Withdrawal Phase and Monotherapy Phase compared with the Titration Phase. Adjunctive Therapy Controlled Trials In the controlled adjunctive therapy epilepsy trials (Study 3, Study 4, and Study 5) , the rate of discontinuation as a result of any adverse reaction was 14% for the 800 mg dose, 25% for the 1200 mg dose, and 7% in subjects randomized to placebo. The adverse reactions most commonly (≥1% in any eslicarbazepine acetate treatment group, and greater than placebo) leading to discontinuation, in descending order of frequency, were dizziness, nausea, vomiting, ataxia, diplopia, somnolence, headache, blurred vision, vertigo, asthenia, fatigue, rash, dysarthria, and tremor. The most frequently reported adverse reactions in patients receiving eslicarbazepine acetate at doses of 800 mg or 1200 mg (≥4% and ≥2% greater than placebo) were dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, blurred vision, and tremor. Table 4 gives the incidence of adverse reactions that occurred in ≥2% of subjects with partial-onset seizures in any eslicarbazepine acetate treatment group and for which the incidence was greater than placebo during the controlled clinical trials. Adverse reactions during titration were less frequent for patients who began therapy at an initial dose of 400 mg for 1 week and then increased to 800 mg compared to patients who initiated therapy at 800 mg.
Drug interactions
Carbamazepine: May need dose adjustment for eslicarbazepine acetate or carbamazepine. ( 2.3 , 5.6 , 7.1 ) Phenytoin: Higher dosage of eslicarbazepine acetate may be necessary and dose adjustment may be needed for phenytoin. ( 2.3 , 7.1 , 7.2 ) Phenobarbital or Primidone: Higher dosage of eslicarbazepine acetate may be necessary. ( 2.3 , 7.1 ) Hormonal Contraceptives: Eslicarbazepine acetate may decrease the effectiveness of hormonal contraceptives. ( 7.4 , 8.3 ) 7.1 Other Antiepileptic Drugs Several AEDs (e.g., carbamazepine, phenobarbital, phenytoin, and primidone) can induce enzymes that metabolize eslicarbazepine acetate and can cause decreased plasma concentrations of eslicarbazepine [see Clinical Pharmacology (12.3) ]. Higher doses of eslicarbazepine acetate may be needed [see Dosage and Administration (2.4) ] . 7.2 CYP2C19 Substrates Eslicarbazepine acetate can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology (12.3) ]. Dose adjustment may be needed. 7.3 CYP3A4 Substrates In vivo studies suggest that eslicarbazepine acetate can induce CYP3A4, decreasing plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., simvastatin, lovastatin) [see Clinical Pharmacology (12.3) ] . Dose adjustment of simvastatin and lovastatin may be needed if a clinically significant change in lipids is noted. 7.4 Oral Contraceptives Because concomitant use of eslicarbazepine acetate and ethinylestradiol and levonorgestrel is associated with lower plasma levels of these hormones, females of reproductive potential should use additional or alternative non-hormonal birth control.
Use in specific populations
Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as eslicarbazepine acetate, during pregnancy. Encourage women who are taking eslicarbazepine acetate during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary Limited available data with eslicarbazepine acetate use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. In oral studies conducted in pregnant mice, rats, and rabbits, eslicarbazepine acetate demonstrated developmental toxicity, including increased incidence of malformations (mice), embryolethality (rats), and fetal growth retardation (all species), at clinically relevant doses (see Data). Advise a pregnant woman of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When eslicarbazepine acetate was orally administered (150, 350, 650 mg/kg/day) to pregnant mice throughout organogenesis, increased incidences of fetal malformations was observed at all doses and fetal growth retardation was observed at the mid and high doses. A no-effect dose for adverse developmental effects was not identified. At the lowest dose tested, plasma eslicarbazepine exposure (C max , AUC) is less than that in humans at the maximum recommended human dose (MRHD, 1600 mg/day). Oral administration of eslicarbazepine acetate (40, 160, 320 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in fetal growth retardation and increased incidences of skeletal variations at the mid and high doses. The no-effect dose (40 mg/kg/day) is less than the MRHD on a mg/m 2 basis. Oral administration to pregnant rats (65, 125, 250 mg/kg/day) throughout organogenesis resulted in embryolethality at all doses, increased incidences of skeletal variations at the mid and high doses, and fetal growth retardation at the high dose. The lowest dose tested (65 mg/kg/day) is less than the MRHD on a mg/m 2 basis. When eslicarbazepine acetate was orally administered to female mice during pregnancy and lactation (150, 350, 650 mg/kg/day), the gestation period was prolonged at the highest dose tested. In offspring, a persistent reduction in offspring body weight and delayed physical development and sexual maturation were observed at the mid and high doses. The lowest dose tested (150 mg/kg/day) is less than the MRHD on a mg/m 2 basis. When eslicarbazepine acetate was orally administered (65, 125, 250 mg/kg/day) to rats during pregnancy and lactation, reduced offspring body weight was seen at the mid and high doses. Delayed sexual maturation and a neurological deficit (decreased motor coordination) were observed at the highest dose tested. The no-effect dose for adverse developmental effects (65 mg/kg/day) is less than the MRHD on a mg/m 2 basis. The rat data are of uncertain relevance to humans because of differences in metabolic profile between species. 8.2 Lactation Eslicarbazepine is present in human milk. The effects of eslicarbazepine acetate on the breastfed infant or on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for eslicarbazepine acetate and any potential adverse effects on the breastfed infant from eslicarbazepine acetate or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Contraception Use of eslicarbazepine acetate with hormonal contraceptives containing ethinylestradiol or levonorgestrel is associated with lower plasma levels of these hormones. Advise women of reproductive potential taking eslicarbazepine acetate who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control [see Drug Interactions (7.4) ]. Infertility Eslicarbazepine acetate was evaluated in rats and mice for potential adverse impact on fertility of the parental and first generation [see Nonclinical Toxicology (13.1) ]. In a fertility study in male and female mice, adverse developmental outcomes were observed in embryos. In a fertility study in male and female rats, impairment of female fertility by eslicarbazepine acetate was shown. 8.4 Pediatric Use Safety and effectiveness of eslicarbazepine acetate have been established in the age groups 4 to 17 years. Use of eslicarbazepine acetate in these age groups is supported by evidence from adequate and well-controlled studies of eslicarbazepine acetate in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data from clinical studies in 393 pediatric patients 4 to 17 years of age [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ]. Safety and effectiveness in pediatric patients below the age of 4 years have not been established. Animal Data In a juvenile animal study in which eslicarbazepine acetate (40, 80, 160 mg/kg/day) was orally administered to young dogs for 10 months starting on postnatal day 21, adverse effects on bone growth (decreased bone mineral content and density) were seen in females at all doses at the end of the dosing period, but not at the end of a 2-month recovery period. Convulsions were seen at the highest dose tested. A no-effect dose for adverse effects in juvenile dogs was not identified. The lowest dose tested is less than the maximum recommended pediatric dose (1200 mg/day) on a body surface area (mg/m 2 ) basis.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as eslicarbazepine acetate, during pregnancy. Encourage women who are taking eslicarbazepine acetate during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org. Risk Summary Limited available data with eslicarbazepine acetate use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. In oral studies conducted in pregnant mice, rats, and rabbits, eslicarbazepine acetate demonstrated developmental toxicity, including increased incidence of malformations (mice), embryolethality (rats), and fetal growth retardation (all species), at clinically relevant doses (see Data). Advise a pregnant woman of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data When eslicarbazepine acetate was orally administered (150, 350, 650 mg/kg/day) to pregnant mice throughout organogenesis, increased incidences of fetal malformations was observed at all doses and fetal growth retardation was observed at the mid and high doses. A no-effect dose for adverse developmental effects was not identified. At the lowest dose tested, plasma eslicarbazepine exposure (C max , AUC) is less than that in humans at the maximum recommended human dose (MRHD, 1600 mg/day). Oral administration of eslicarbazepine acetate (40, 160, 320 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in fetal growth retardation and increased incidences of skeletal variations at the mid and high doses. The no-effect dose (40 mg/kg/day) is less than the MRHD on a mg/m 2 basis. Oral administration to pregnant rats (65, 125, 250 mg/kg/day) throughout organogenesis resulted in embryolethality at all doses, increased incidences of skeletal variations at the mid and high doses, and fetal growth retardation at the high dose. The lowest dose tested (65 mg/kg/day) is less than the MRHD on a mg/m 2 basis. When eslicarbazepine acetate was orally administered to female mice during pregnancy and lactation (150, 350, 650 mg/kg/day), the gestation period was prolonged at the highest dose tested. In offspring, a persistent reduction in offspring body weight and delayed physical development and sexual maturation were observed at the mid and high doses. The lowest dose tested (150 mg/kg/day) is less than the MRHD on a mg/m 2 basis. When eslicarbazepine acetate was orally administered (65, 125, 250 mg/kg/day) to rats during pregnancy and lactation, reduced offspring body weight was seen at the mid and high doses. Delayed sexual maturation and a neurological deficit (decreased motor coordination) were observed at the highest dose tested. The no-effect dose for adverse developmental effects (65 mg/kg/day) is less than the MRHD on a mg/m 2 basis. The rat data are of uncertain relevance to humans because of differences in metabolic profile between species.
Pediatric use
8.4 Pediatric Use Safety and effectiveness of eslicarbazepine acetate have been established in the age groups 4 to 17 years. Use of eslicarbazepine acetate in these age groups is supported by evidence from adequate and well-controlled studies of eslicarbazepine acetate in adults with partial-onset seizures, pharmacokinetic data from adult and pediatric patients, and safety data from clinical studies in 393 pediatric patients 4 to 17 years of age [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ]. Safety and effectiveness in pediatric patients below the age of 4 years have not been established. Animal Data In a juvenile animal study in which eslicarbazepine acetate (40, 80, 160 mg/kg/day) was orally administered to young dogs for 10 months starting on postnatal day 21, adverse effects on bone growth (decreased bone mineral content and density) were seen in females at all doses at the end of the dosing period, but not at the end of a 2-month recovery period. Convulsions were seen at the highest dose tested. A no-effect dose for adverse effects in juvenile dogs was not identified. The lowest dose tested is less than the maximum recommended pediatric dose (1200 mg/day) on a body surface area (mg/m 2 ) basis. A separate juvenile animal study was conducted to assess possible adverse effects on the immune system. Eslicarbazepine acetate (10, 40, 80 mg/kg/day) was orally administered to young dogs for 17 weeks starting on postnatal day 21. No effects on the immune system were observed.
Geriatric use
8.5 Geriatric Use There were insufficient numbers of patients ≥65 years old enrolled in the controlled adjunctive epilepsy trials (N=15) to determine the efficacy of eslicarbazepine acetate in this patient population. The pharmacokinetics of eslicarbazepine acetate were evaluated in elderly healthy subjects (N=12) (Figure 1). Although the pharmacokinetics of eslicarbazepine are not affected by age independently, dose selection should take in consideration the greater frequency of renal impairment and other concomitant medical conditions and drug therapies in the elderly patient. Dose adjustment is necessary if CrCl is <50 mL/min [see Clinical Pharmacology (12.3) ].
Overdosage
10.1 Signs, Symptoms, and Laboratory Findings of Acute Overdose in Humans Symptoms of overdose are consistent with the known adverse reactions of eslicarbazepine acetate and include hyponatremia (sometimes severe), dizziness, nausea, vomiting, somnolence, euphoria, oral paraesthesia, ataxia, walking difficulties, and diplopia. The maximum dosage studied in open-label adult monotherapy treatment following withdrawal of concomitant AEDs was 2400 mg once daily. 10.2 Treatment or Management of Overdose There is no specific antidote for overdose with eslicarbazepine acetate. Symptomatic and supportive treatment should be administered as appropriate. Removal of the drug by gastric lavage and/or inactivation by administering activated charcoal should be considered. Standard hemodialysis procedures result in partial clearance of eslicarbazepine acetate. Hemodialysis may be considered based on the patient’s clinical state or in patients with significant renal impairment.
Description
The chemical name of eslicarbazepine acetate is (S)-10-Acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide. Eslicarbazepine acetate is a dibenz[b,f]azepine-5-carboxamide derivative. Its molecular formula is C 17 H 16 N 2 O 3 and its molecular weight is 296.32. The chemical structure is: Eslicarbazepine acetate, USP is a white to off-white, powder. It is soluble in methanol and acetonitrile and practically insoluble in hexane. Each eslicarbazepine acetate tablet contains 200 mg, 400 mg, 600 mg or 800 mg of eslicarbazepine acetate, USP and the following inactive ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate, povidone and sodium starch glycolate. str
Mechanism of action
12.1 Mechanism of Action Eslicarbazepine acetate 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.
How supplied
16.1 How Supplied Eslicarbazepine Acetate Tablets 200 mg are white to off-white, oblong shape, biconvex, uncoated tablet debossed with ‘E’ on the left side and ‘T’ on the right side of score line on one side and ‘200’ on the other side. Eslicarbazepine Acetate Tablets 400 mg are white to off-white, round shape, biconvex, uncoated tablet debossed with ‘ET’ on one side and ‘400’ on the other side. Eslicarbazepine Acetate Tablets 600 mg are white to off-white, oblong shape, biconvex, uncoated tablet debossed with ‘E’ on the left side and ‘T’ on the right side of score line on one side and ‘600’ on the other side. Eslicarbazepine Acetate Tablets 800 mg are white to off-white, oblong shape, biconvex, uncoated tablet debossed with ‘E’ on the left side and ‘T’ on the right side of score line on one side and ‘800’ on the other side. Tablets are supplied in the following strengths and package configurations (Table 6): Table 6: Package Configuration for Eslicarbazepine Acetate Tablets Tablet Strength Package Configuration NDC Code 200 mg Bottles of 30 59651-533-30 400 mg Bottles of 30 59651-534-30 600 mg Bottles of 60 59651-535-60 800 mg Bottles of 30 59651-536-30 16.2 Storage and Handling Store eslicarbazepine acetate tablets at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Patient information
See FDA-approved patient labeling ( Medication Guide ). Inform patients and caregivers of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking eslicarbazepine acetate tablets. Instruct patients and caregivers that eslicarbazepine acetate tablets should only be taken as prescribed. Suicidal Behavior and Ideation Counsel patients, their caregivers, and families that AEDs, including eslicarbazepine acetate tablets, may increase the risk of suicidal thoughts and behavior and advise them of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.1) ]. Serious Dermatologic Reactions Advise patients and caregivers about the risk of potentially fatal serious skin reactions. Educate patients and caregivers about the signs and symptoms that may signal a serious skin reaction. Instruct patients and caregivers to consult with their healthcare provider immediately if a skin reaction occurs during treatment with eslicarbazepine acetate tablets [see Warnings and Precautions (5.2) ]. DRESS/Multi-organ Hypersensitivity Instruct patients and caregivers that a fever associated with signs of other organ system involvement (e.g., rash, lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their healthcare provider immediately [see Warnings and Precautions (5.3) ]. Anaphylactic Reactions and Angioedema Advise patients and caregivers of life threatening symptoms suggesting anaphylaxis or angioedema (swelling of the face, eyes, lips, tongue, or difficulty in swallowing or breathing) that can occur with eslicarbazepine acetate tablets. Instruct them to immediately report these symptoms to their healthcare provider [see Warnings and Precautions (5.4) ]. Hyponatremia Advise patients and caregivers that eslicarbazepine acetate tablets may reduce serum sodium concentrations, especially if they are taking other medications that can lower sodium. Advise patients and caregivers to report symptoms of low sodium such as nausea, tiredness, lack of energy, irritability, confusion, muscle weakness/spasms, or more frequent or more severe seizures [see Warnings and Precautions (5.5) ]. Neurological Adverse Reactions Counsel patients and caregivers that eslicarbazepine acetate tablets may cause dizziness, gait disturbance, somnolence/fatigue, cognitive dysfunction, and visual changes. These adverse reactions, if observed, are more likely to occur during the titration period compared to the maintenance period. Advise patients not to drive or operate machinery until they have gained sufficient experience on eslicarbazepine acetate tablets to gauge whether it adversely affects their ability to drive or operate machinery [see Warnings and Precautions (5.6) ]. Withdrawal of Eslicarbazepine Acetate Tablets Advise patients and caregivers not to discontinue use of eslicarbazepine acetate tablets without consulting with their healthcare provider. Eslicarbazepine acetate tablets should be gradually withdrawn to minimize the potential of increased seizure frequency and status epilepticus [see Warnings and Precautions (5.7) ]. Hematologic Adverse Reactions Advise patients and caregivers that there have been rare reports of blood disorders reported in patients treated with eslicarbazepine acetate tablets. Instruct patients to immediately consult with their physician if they experience symptoms suggestive of blood disorders [see Warnings and Precautions (5.10) ]. Interaction with Oral Contraceptives Inform patients and caregivers that eslicarbazepine acetate tablets can significantly decrease the effectiveness of hormonal contraceptives. Recommend that female patients of childbearing potential use additional or alternative non-hormonal forms of contraception during treatment with eslicarbazepine acetate tablets and after treatment has been discontinued for at least one menstrual cycle or until otherwise instructed by their healthcare provider [see Drug Interactions (7.3 , 7.4) ]. Pregnancy Registry Encourage patients to enroll in the North American Antiepileptic Drug Pregnancy Registry if they become pregnant. This Registry is collecting information about the safety of AEDs during pregnancy. To enroll, patients can call 1-888-233-2334 (toll-free) [see Use in Specific Populations (8.1) ]. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Issued: July 2025
Label text from the FDA structured product label by Aurobindo Pharma Limited (revised Aug 7, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Eslicarbazepine Acetate in 36 products
Eslicarbazepine acetate NDC products (36)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 60505-4661 | Eslicarbazepine Acetate 800 mg/1 Tablet | Apotex Corp. | ANDA |
| 60505-4660 | Eslicarbazepine Acetate 600 mg/1 Tablet | Apotex Corp. | ANDA |
| 60505-4659 | Eslicarbazepine Acetate 400 mg/1 Tablet | Apotex Corp. | ANDA |
| 60505-4658 | Eslicarbazepine Acetate 200 mg/1 Tablet | Apotex Corp. | ANDA |
| 67877-588 | Eslicarbazepine Acetate 800 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 67877-587 | Eslicarbazepine Acetate 600 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 67877-586 | Eslicarbazepine Acetate 400 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 67877-585 | Eslicarbazepine Acetate 200 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 59651-533 | Eslicarbazepine Acetate 200 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-536 | Eslicarbazepine Acetate 800 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-535 | Eslicarbazepine Acetate 600 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 59651-534 | Eslicarbazepine Acetate 400 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 31722-428 | Eslicarbazepine Acetate 200 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-429 | Eslicarbazepine Acetate 400 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-430 | Eslicarbazepine Acetate 600 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-431 | Eslicarbazepine Acetate 800 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 43598-687 | Eslicarbazepine Acetate 800 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 43598-686 | Eslicarbazepine Acetate 600 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 43598-685 | Eslicarbazepine Acetate 400 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 43598-684 | Eslicarbazepine Acetate 200 mg/1 Tablet | Dr.Reddys Laboratories Inc | ANDA |
| 51407-780 | Eslicarbazepine Acetate 400 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-781 | Eslicarbazepine Acetate 600 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-782 | Eslicarbazepine Acetate 800 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-779 | Eslicarbazepine Acetate 200 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 59746-719 | Eslicarbazepine Acetate 600 mg/1 Tablet | Jubilant Cadista Pharmaceuticals Inc. | ANDA |
| 59746-720 | Eslicarbazepine Acetate 800 mg/1 Tablet | Jubilant Cadista Pharmaceuticals Inc. | ANDA |
| 59746-718 | Eslicarbazepine Acetate 400 mg/1 Tablet | Jubilant Cadista Pharmaceuticals Inc. | ANDA |
| 59746-717 | Eslicarbazepine Acetate 200 mg/1 Tablet | Jubilant Cadista Pharmaceuticals Inc. | ANDA |
| 68180-293 | Eslicarbazepine Acetate 800 mg/1 Tablet | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-290 | Eslicarbazepine Acetate 200 mg/1 Tablet | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-291 | Eslicarbazepine Acetate 400 mg/1 Tablet | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-292 | Eslicarbazepine Acetate 600 mg/1 Tablet | Lupin Pharmaceuticals, Inc. | ANDA |
| 13668-541 | Eslicarbazepine Acetate 800 mg/1 Tablet | Torrent Pharmaceuticals Limited | ANDA |
| 13668-540 | Eslicarbazepine Acetate 600 mg/1 Tablet | Torrent Pharmaceuticals Limited | ANDA |
| 13668-539 | Eslicarbazepine Acetate 400 mg/1 Tablet | Torrent Pharmaceuticals Limited | ANDA |
| 13668-538 | Eslicarbazepine Acetate 200 mg/1 Tablet | Torrent Pharmaceuticals Limited | ANDA |
Frequently asked questions
What is Eslicarbazepine acetate used for?
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 )
What are the side effects of Eslicarbazepine acetate?
The following adverse reactions are described in more detail in the Warnings and Precautions section of the label: Suicidal Behavior and Ideation [see Warnings and Precautions (5.1) ] Serious Dermatologic Reactions [see Warnings and Precautions (5.2) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.3) ] Anaphylactic… See the full label for the complete list.
Who makes Eslicarbazepine acetate?
Eslicarbazepine acetate is listed by 9 labelers in the FDA NDC directory, including Apotex Corp., Ascend Laboratories, LLC, Aurobindo Pharma Limited, Camber Pharmaceuticals, Inc..