*2 separate analyses: 2005 Behavioral Risk Factor Surveillance System Survey of noninstitutionalized adults ≥18 years of age from 19 states, 1.65% reported they had been told they had epilepsy or a seizure disorder by a doctor4 vs 7.7% of residents age 65 and older in US Medicare/Medicaid-certified nursing homes from 2003-2007.3
Trial design: 525 patients (age 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997 were prospectively studied. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structure abnormality), or cryptogenic (resulting from an unknown underlying cause). Drug doses were adjusted as clinical circumstances dictated, with particular attention paid to efficacy and tolerability. Patients were treated with a single drug when possible, as is recommended practice. Treatment was changed to another drug if seizures remained uncontrolled or if the patient had an idiosyncratic reaction or intolerable side effects. A combination of drugs was used in patients whose epilepsy remained uncontrolled despite treatment with 2 or 3 single drugs.5
†These data are generally accepted and have been replicated in multiple studies, including Brodie MJ, et al.6
‡Patients were considered to be seizure free if they had not had any seizures for at least 1 year.5
1. England MJ, et al. Epilepsy Across the Spectrum: Promoting Health and Understanding. Washington, DC: The National Academies Press; 2012.
2. Zack MW, Kobau R. National and state estimates of the numbers of adults and children with active epilepsy—United States, 2015. MMWR Morb Mortal Wkly Rep. 2017;66:821-825.
3. Birnbaum AK, Leppik IE, Svensden K, Eberly LE. Prevalence of epilepsy/seizures as a comorbidity of neurologic disorders in nursing homes. Neurology. 2017;88:750-757.
4. Kobau R, Luo Y, Zack MM, Helmers S, Thurman DJ. Epilepsy in adults and access to care–United States, 2010. MMWR Morb Mortal Wkly Rep. 2012;61:909-913.
5. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-319.
6. Brodie MJ, Barry SJE, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78:1548-1554.
7. Cramer JA, Glassman M, Rienzi V. The relationship between poor medication compliance and seizures. Epilepsy Behav. 2002;3:338-342.
8. Wagner ML, Murad D, Patel D. Compliance in epilepsy: a review. US Pharm. 2001;26:33.
Contraindications: APTIOM is contraindicated in patients with a hypersensitivity to eslicarbazepine acetate or oxcarbazepine.
Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including APTIOM, increase the risk of suicidal thoughts or behavior. Anyone considering prescribing APTIOM 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. 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. Patients and caregivers should also be advised to be alert to these behavioral changes and to immediately report them to the health care provider.
Serious Dermatologic Reactions, including Stevens‐Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with APTIOM 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 APTIOM. Should a patient develop a dermatologic reaction while using APTIOM, discontinue APTIOM use unless it is clearly not drug related.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, has been reported in patients taking APTIOM. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement. If this reaction is suspected, treatment with APTIOM should be discontinued.
Anaphylactic Reactions and Angioedema: Rare cases of anaphylaxis and angioedema have been reported in patients taking APTIOM. Anaphylaxis and angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions, the drug should be discontinued. Patients with a prior anaphylactic‐type reaction after treatment with either oxcarbazepine or APTIOM should not be treated with APTIOM.
Hyponatremia: Clinically significant hyponatremia (sodium <125 mEq/L) and syndrome of inappropriate antidiuretic hormone secretion (SIADH) can develop in patients taking APTIOM. Measurement of serum sodium and chloride levels should be considered during maintenance treatment with APTIOM, particularly if the patient is receiving other medications known to decrease serum sodium levels. Depending on the severity of hyponatremia, the dose of APTIOM may need to be reduced or discontinued.
Neurological Adverse Reactions: APTIOM causes dose‐dependent increases in the following reactions (dizziness, disturbance in gait and coordination, somnolence, fatigue, and visual changes). There was an increased risk of dizziness, disturbance in gait and coordination, and visual changes during the titration period (compared to maintenance treatment), and there may be an increased risk of these adverse reactions in patients 60 years of age and older compared to younger adults. APTIOM causes dose-dependent increases in cognitive dysfunction-related events in adults (memory impairment, disturbance in attention, amnesia, confusional state, aphasia, speech disorder, slowness of thought, disorientation, and psychomotor retardation). The incidences of dizziness and diplopia were greater with concomitant use of APTIOM and carbamazepine compared to the use of APTIOM without carbamazepine.
Prescribers should advise patients against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of APTIOM is known.
Withdrawal of AEDs: As with all AEDs, APTIOM should be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus, but if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.
Drug Induced Liver Injury: Hepatic effects, ranging from mild to moderate elevations in transaminases (>3 times the upper limit of normal) to rare cases with concomitant elevations of total bilirubin (>2 times the upper limit of normal) have been reported with APTIOM use. Baseline evaluations of liver laboratory tests are recommended. APTIOM should be discontinued in patients with jaundice or other evidence of significant liver injury.
Abnormal Thyroid Function Tests: Dose‐dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking APTIOM. These changes were not associated with other abnormal thyroid function tests suggesting hypothyroidism. Abnormal thyroid function tests should be clinically evaluated.
Hematologic Adverse Reactions: Rare cases of pancytopenia, agranulocytosis, and leukopenia have been reported during postmarketing use in patients treated with APTIOM. Discontinuation of APTIOM should be considered in patients who develop pancytopenia, agranulocytosis, or leukopenia.
Most Common Adverse Reactions: The most common adverse reactions in adult patients receiving APTIOM (≥4% and ≥2% greater than placebo) were dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, blurred vision, and tremor. Adverse reactions in pediatric patients are similar to those seen in adult patients.
Safety and Efficacy in Patients <4 Years of Age: Safety and effectiveness in patients below 4 years of age have not been established.
Some adverse reactions occur more frequently when patients take APTIOM adjunctively with carbamazepine. When APTIOM and carbamazepine are taken concomitantly, the dose of APTIOM or carbamazepine may need to be adjusted based on efficacy and tolerability. APTIOM should not be taken as an adjunctive therapy with oxcarbazepine. For patients taking other enzyme‐inducing AEDs (i.e., phenobarbital, phenytoin, and primidone), higher doses of APTIOM may be needed.
A dose reduction is recommended in patients with moderate and severe renal impairment (i.e., creatinine clearance <50 mL/min).
Dose adjustments are not required in patients with mild to moderate hepatic impairment. Use of APTIOM in patients with severe hepatic impairment has not been studied, and use in these patients is not recommended.
Concomitant use of APTIOM and oral contraceptives containing ethinylestradiol and levonorgestrel is associated with lower plasma levels of these hormones. Patients should use additional or alternative non‐hormonal birth control during APTIOM treatment and after discontinuation of APTIOM for one menstrual cycle, or until otherwise instructed.
Indications and Usage
Aptiom® (eslicarbazepine acetate) is indicated for the treatment of partial‐onset seizures in patients 4 years of age and older.
Before prescribing APTIOM, please read the Full Prescribing Information.