FDA approved eslicarbazepine acetate on November 8, 2013 as an adjunctive treatment of partial-onset seizures in adults.
Eslicarbazepine acetate (Aptiom, Sunovion Pharmaceuticals, Inc) was approved by the FDA on November 8, 2013 as an adjunctive treatment of partial-onset seizures in adults. A pro-drug, after oral administration, eslicarbazepine acetate is extensively metabolized via first pass metabolism to the major active metabolite, eslicarbazepine. Eslicarbazepine is a voltage-gated sodium channel inhibitor.
The FDA approved eslicarbazepine acetate based on the findings of three double-blind, placebo-controlled trials. An eight-week baseline assessment of seizure frequency identified participants for inclusion. Participants had partial-onset seizures with or without secondary generalization and were not adequately controlled on concomitant antiepileptic drugs. Oxcarbazepine use was not allowed during the studies.
Participants who demonstrated an average of four or more seizures within 28 days without a seizure-free period greater than 21 days continued on to the titration and maintenance phases of study (median of eight seizures per 28 days).
Two studies evaluated 400 mg, 800 mg, and 1200 mg doses compared to placebo. The third study compared 800 mg and 1200 mg to placebo. Seizure frequency during the maintenance period served as the primary efficacy end point for all the studies. Secondary efficacy end points included the proportion of participants experiencing a 50% reduction in seizure frequency over four weeks during the 12-week maintenance phase and the overall change in seizure frequency from baseline.
Overall, the three studies demonstrated a significant dose-related treatment efficacy compared to placebo; the 1200 mg dosage demonstrated efficacy in all three studies, 800 mg dosage demonstrated efficacy in two studies, and 400 mg dose failed to demonstrate significant treatment efficacy. Forty-one percent of patients administered 1200 mg and 32% of patients administered 800 mg of eslicarbazepine acetate experienced a minimum 50% reduction in seizure frequency during the maintenance phase compared to 22% of participants administered placebo. I
n all studies, participants administered 800 mg or 1200 mg of eslicarbazepine acetate experienced a greater than median percent reduction from baseline seizure frequency compared to those administered placebo.
The most common adverse reactions associated with eslicarbazepine acetate include dizziness, somnolence, headache, nausea, vomiting, fatigue, vertigo, ataxia, tremor, and visual disturbances (blurred vision, diplopia). The rate of study discontinuation demonstrated a dose-related relationship. The manufacturer recommends monitoring for rare but serious dermatological reactions, multiorgan hypersensitivity, anaphylaxis, and angioedema, which have occurred with use of eslicarbazepine acetate.
Eslicarbazepine acetate is contraindicated in patients who have experienced any of these reactions with use of eslicarbazepine or oxcarbazepine. Baseline liver function tests are recommended. Serum sodium levels should be monitored in patients demonstrating symptoms of hyponatremia or taking other medications, which may decrease sodium levels.
As with other anti-epilieptic drugs, eslicarbazepine acetate may increase the risk of suicidal thoughts and behaviors. All patients should be monitored for changes to mood, behavior, or depression.
Any pregnant patient taking eslicarbazepine acetate should be enrolled in the North American Antiepileptic Drug Pregnancy Registry, www.aedpregnancyregistry.org.
The recommended starting dose is 400 mg daily for one week. The dose may then be increased to the recommended maintenance dose of 800 mg daily. If needed, the dose may be further increased after one week to the maximum recommended dose, 1200 mg daily.
In patients with renal dysfunction (CrCl <50mL/min), treatment should be initiated at 200 mg of eslicarbazepine acetate daily. After two weeks, the dose may be increased to the recommended maintenance dose of 400 mg daily. If needed, the dose may be further increased after one week to 600 mg, the maximum recommended dose for patients with significant renal impairment.
Eslicarbazepine acetate should not be used in patients with severe hepatic impairment. Eslicarbazepine has demonstrated clinically significant drug interactions with other enzyme inducing antiepileptic drugs. Concomitant use with phenobarbital, primidone, phenytoin, and carbamazepine may require higher doses of eslicarbazepine acetate and/or dose adjustment of other antiepileptic medications.
Eslicarbazepine acetate can decrease the effectiveness of hormonal contraceptive medications. Patients should be counseled to use alternative birth control methods while on eslicarbazepine acetate.
Abrupt discontinuation of eslicarbazepine should be avoided to minimize the risk of increased seizure frequency and status epilepticus.
Eslicarbazepine acetate may be taken without consideration of food.
Kathryn Wheeler, PharmD, is assistant clinical professor of pharmacy practice, University of Connecticut School of Pharmacy, Storrs, Conn.