Potassium channel opener.
Ezogabine 50mg, 200mg, 300mg, 400mg; tablets.
Adjunctive treatment of partial-onset seizures in patients ≥18 years old.
The mechanism by which ezogabine exerts its therapeutic effects has not been fully elucidated. In vitro studies indicate that ezogabine enhances transmembrane potassium currents mediated by the KCNQ (Kv 7.2 to 7.5) family of ion channels. By activating KCNQ channels, ezogabine is thought to stabilize the resting membrane potential and reduce brain excitability. In vitro studies suggest that ezogabine may also exert therapeutic effects through augmentation of GABA-mediated currents.
The efficacy of Potiga as adjunctive therapy in partial-onset seizures was established in 3 multicenter, randomized, double-blind, placebo-controlled studies in 1,239 adult patients. The primary endpoint consisted of the percent change in seizure frequency from baseline in the double-blind treatment phase.
Patients enrolled in the studies had partial onset seizures w/ or w/o secondary generalization and were not adequately controlled with 1 to 3 concomitant AEDs, w/ or w/o concomitant vagus nerve stimulation. More than 75% of patients were taking 2 or more concomitant AEDs. During an 8-week baseline period, patients experienced at least 4 partial onset seizures per 28 days on average with no seizure-free period exceeding 3 to 4 weeks. Mean duration of epilepsy was 22 years. Across the 3 studies, the median baseline seizure frequency ranged from 8 to 12 seizures per month. The criteria for statistical significance was P<0.05.
Patients were randomized to the total daily maintenance dosages of 600mg/day, 900mg/day, or 1,200mg/day, each given in 3 equally divided doses. During the titration phase of all 3 studies, treatment was initiated at 300mg/day and increased in weekly increments of 150mg/day to the target maintenance dosage. A statistically significant effect was observed with Potiga at doses of 600mg/day (Study 1), at 900mg/day (Studies 1 and 3), and at 1,200mg/day (Studies 2 and 3) in the median percent reduction in 28-day seizure frequency (baseline to double-blind phase) as compared with placebo across all 3 studies.
Swallow whole. Give in 3 equally divided doses daily. ≥18 years: initially 300mg/day for 1 week; titrate at weekly intervals by no more than 150mg/day up to a maintenance dose of 600–1200mg/day. Elderly (>65 years) or hepatic impairment (Child-Pugh 7–9): initially 150mg/day; max 750mg/day. Renal impairment (CrCl <50mL or ESRD on dialysis) or hepatic impairment (Child-Pugh >9): initially 150mg/day; max 600mg/day. See literature.
Children: <18 years: not established.
Increased risk of urinary retention; monitor closely in patients with BPH, cognitively impaired, or concomitant medications that may affect voiding (eg, anticholinergics). Monitor for neuropsychiatric symptoms (eg, confusional state, psychosis, hallucinations), dizziness, somnolence. Monitor QT interval in patients with known prolonged QT interval, CHF, ventricular hypertrophy, hypokalemia, or hypomagnesemia. Monitor for emergence or worsening of depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior. Avoid abrupt cessation; withdraw gradually over at least 3 weeks. Pregnancy (Cat. C). Nursing mothers: not recommended.
Caution with drugs known to increase the QT interval. Plasma levels reduced by concomitant phenytoin or carbamazepine; consider increasing ezogabine dose. May potentiate digoxin; monitor. Increased exposure with alcohol; caution. May interfere in clinical lab assays of serum and urine bilirubin.
Dizziness, somnolence, fatigue, confusional state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, memory impairment, asthenia, blurred vision, gait disturbance, aphasia, dysarthria, balance disorder.