Eslicarbazepine Acetate

FDA Drug Information • Also known as: Aptiom, Eslicarbazepine Acetate

Brand Names: Aptiom, Eslicarbazepine Acetate
Route: ORAL
Dosage Form: TABLET
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION The chemical name of APTIOM (eslicarbazepine acetate) is (S)-10-Acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide. APTIOM 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: APTIOM is a white to off-white, odorless crystalline solid. It is insoluble in hexane, very slightly soluble in aqueous solvents and soluble in organic solvents such as acetone, acetonitrile, and methanol. Each APTIOM tablet contains 200 mg, 400 mg, 600 mg or 800 mg of eslicarbazepine acetate and the following inactive ingredients: croscarmellose sodium, magnesium stearate, and povidone. Chemical structure

What Is Eslicarbazepine Acetate Used For?

1 INDICATIONS AND USAGE APTIOM is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. APTIOM is indicated for the treatment of partial-onset seizures in patients 4 years of age and older. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Adult Patients: The recommended initial dosage of APTIOM 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 APTIOM 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 APTIOM either as whole or as crushed tablets. Instruct patients to take APTIOM either with or without food. The APTIOM 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 APTIOM 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 APTIOM 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 APTIOM 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 APTIOM 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: APTIOM 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 APTIOM adjunctively with carbamazepine [see Warnings and Precautions ( 5.6 )] . However, carbamazepine...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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 APTIOM (≥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 Sumitomo Pharma America, Inc. at 1-877-737-7226 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 APTIOM, 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 APTIOM, 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 APTIOM. 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 APTIOM 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 APTIOM) 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 APTIOM 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 APTIOM at doses of 800 mg or 1200 mg (≥4% and ≥2% greater than placebo) were dizziness,...

Drug Interactions

7 DRUG INTERACTIONS Carbamazepine: May need dose adjustment for APTIOM or carbamazepine. ( 2.3 , 5.6 , 7.1 ) Phenytoin: Higher dosage of APTIOM may be necessary and dose adjustment may be needed for phenytoin. ( 2.3 , 7.1 , 7.2 ) Phenobarbital or Primidone: Higher dosage of APTIOM may be necessary. ( 2.3 , 7.1 ) Hormonal Contraceptives: APTIOM 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 APTIOM and can cause decreased plasma concentrations of eslicarbazepine [see Clinical Pharmacology ( 12.3 )]. Higher doses of Aptiom may be needed [see Dosage and Administration ( 2.4 )]. 7.2 CYP2C19 Substrates APTIOM 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 APTIOM 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 APTIOM 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.

Contraindications

4 CONTRAINDICATIONS APTIOM is 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 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as APTIOM, during pregnancy. Encourage women who are taking APTIOM 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 APTIOM 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 2-4% and 15-20%, 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...

Overdosage

10 OVERDOSAGE 10.1 Signs, Symptoms, and Laboratory Findings of Acute Overdose in Humans Symptoms of overdose are consistent with the known adverse reactions of APTIOM 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 APTIOM. 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 APTIOM. Hemodialysis may be considered based on the patient's clinical state or in patients with significant renal impairment.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied APTIOM tablets are white, oblong and with functional scoring on one side (200 mg, 600 mg, and 800 mg) or white, circular bi-convex and plain on one side (400 mg) and identified with strength-specific one-sided engraving on the other side, “ESL 200” (200 mg), “ESL 400” (400 mg), “ESL 600” (600 mg), or “ESL 800” (800 mg). Tablets are supplied in the following strengths and package configurations ( Table 6 ): Table 6: Package Configuration for APTIOM Tablets Tablet Strength Package Configuration NDC Code 200 mg Bottles of 30 63402-202-30 400 mg Bottles of 30 63402-204-30 600 mg Bottles of 60 63402-206-60 800 mg Bottles of 30 63402-208-30 16.2 Storage and Handling Store APTIOM tablets at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. 16.1 How Supplied APTIOM tablets are white, oblong and with functional scoring on one side (200 mg, 600 mg, and 800 mg) or white, circular bi-convex and plain on one side (400 mg) and identified with strength-specific one-sided engraving on the other side, “ESL 200” (200 mg), “ESL 400” (400 mg), “ESL 600” (600 mg), or “ESL 800” (800 mg). Tablets are supplied in the following strengths and package configurations ( Table 6 ): Table 6: Package Configuration for APTIOM Tablets Tablet Strength Package Configuration NDC Code 200 mg Bottles of 30 63402-202-30 400 mg Bottles of 30 63402-204-30 600 mg Bottles of 60 63402-206-60 800 mg Bottles of 30 63402-208-30

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.