Drug Therapy in Epilepsy

Ezogabine and Retigabine Combination Safe, Effective Adjunctive Therapy for Partial-onset Seizures.
• A combination of the two anti-epileptic drugs ezogabine (EZG) and retigabine (RTG) is an effective adjunctive therapy in adults with partial-onset seizures.
• An open-label, uncontrolled study of flexibly dosed EZG/RTG tested this combination in 203 adults with partial-onset seizures who had been taking either carbamazepine/oxcarbazepine, lamotrigine, levetiracetam, or valproic acid.
• The dose of EZG/RTG prescribed most frequently was 600 mg/day.

High Responder Rate Near 50%.
• The overall responder rate (≥50% reduction in partial seizure frequency) was 44.5%.
• The responder rate ranged from 32% in the lamotrigine group to 57% in the valproic acid group.
• The responder rate decreased with increased number of previously failed antiepileptic drugs.
• The safety and tolerability of EZG/RTG were similar to that reported previously.ReferenceLerche H, et al. Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures. Seizure. 2015;30:93–100. See abstract here.

Fycompa® Approved as Adjunctive Therapy for Primary Generalized Tonic-Clonic Seizures.
• Generalized tonic-clonic seizures can cause significant injury to patients from sudden falls.
• This type of seizure is the most important risk factor associated with sudden unexpected death in epilepsy (SUDEP), making it one of the most severe forms of epileptic seizures.
• The US Food and Drug Administration (FDA) expanded the approval for the use of the anti-epileptic agent Fycompa (perampanel hydrate) as an adjunctive treatment of primary generalized tonic-clonic seizures in patients 12 years of age and older with epilepsy.

Fycompa Significantly Reduces Seizure Frequency.
• The FDA approved the indication expansion based on a placebo-controlled clinical phase III study of 164 patients aged 12 years and older.
• Fycompa led to a statistically significant reduction in primary generalized tonic-clonic seizure frequency (76.5%) compared with placebo (38.4%).
• The responder rate in the Fycompa group was 64.2% compared to 39.5% in the placebo group.

Fycompa Extends Seizure-free Period.
• More patients treated with Fycompa (30.9%) were free of seizures during the 13-week maintenance period as compared to those on placebo (12.3%).
• The most common adverse events for Fycompa were dizziness, fatigue, headache, somnolence, and irritability.
• With this indication expansion, Fycompa can now be used as an adjunctive treatment for primary, in addition to, secondary generalized tonic-clonic seizures.ReferenceU.S. FDA approves Eisai’s antiepileptic agent Fycompa® as adjunctive treatment for primary generalized tonic-clonic seizures. 22 June 2015. http://www.eisai.com/news/news201543.html. See release here.

Study of Eslicarbazepine in Post-stroke Seizure Patients.
• Eslicarbazepine's long half-life of 20-24 hours permits once-daily dosing, which could be a tremendous benefit for the many seizure patients who have difficulty with adherence.
• However, hyponatremia can occur with eslicarbazepine, just as with other anti-epileptics such as carbamazepine and oxcarbazepine.
• These researchers evaluated the safety of eslicarbazepine acetate in new onset elderly post-stroke seizure patients, especially with respect to hyponatremia, in a 2-year, single-center, open-label, observational study of 32 patients.

Eslicarbazepine Leads to High Frequency of Hyponatremia.
• Researchers found a high frequency of hyponatremia (12.5%) following eslicarbazepine therapy.
• They conclude that eslicarbazepine-related hyponatremia occurs in elderly stroke patients with comorbidities, and is not dose-related.
• The authors suggest that elderly patients on eslicarbazepine therapy need to have their sodium levels monitored. ReferenceGupta DK, et al. Hyponatremia following esclicarbazepine therapy. Seizure. July 2015; 29:11–14. See abstract here.

Take-home Messages.
• Ezogabine/retigabine is an effective adjunctive therapy in adults with partial-onset seizures.
• The FDA granted an indication expansion to Fycompa. The drug can now be used for both primary and secondary generalized tonic-clonic seizures.
• Seizure patients taking eslicarbazepine who develop hyponatremia should have dose reductions or be withdrawn from the drug.