Abstracts

Rationale: A recent FDA alert described the potential for skin and retinal abnormalities in patients taking ezogabine (EZG). This study was undertaken to determine how many patients in our single academic epilepsy center reported EZG-related side effects and how many had chosen to discontinue the drug in response to the FDA alert.Methods: All patients on EZG in our outpatient clinic were identified through query of our clinical database. We developed a standardized screening protocol and patient letter based on the FDA recommendations and those of the ophthalmology department at our institution. In our standardized protocol, patients were contacted by phone and asked about EZG dose, change in seizure frequency and drug-related side effects. They were also given scripted information on recommendations regarding eye examination and offered immediate follow-up with a neurologist, as well as ophthalmology referrals.Results: Twenty-seven patients on EZG were identified, three of which could not be reached for follow up. Data analysis was performed for the remaining 24 patients. Mean age was 35 years (range 20-56), 10 patients were women. Average duration of epilepsy was 24.75 years (range 10-47 years) and median duration of EZG use was 10 months (range 0.5-15 months), with a median total daily dose of 450mg (range 25-1100mg). The total cumulative dose median was 162g (range 1.2-351g). 67% (n=16) of patients were still taking EZG. Of those who stopped (n=8), 88% (n=7) did so because of side effects and 12% (n=1) because of increased seizures. One half (n=12) of patients reported a reduction in seizure frequency and one became seizure free. 75% (n=3) reported their seizures were less intense and/or shorter. 17% (n=1) reported mood improvement. Overall, 67% (n=16) developed side effects: 17% (n=4) described visual changes, 13% (n=3) with urinary retention, 46% (n=11) with dizziness, anxiety, sedation, weight gain, GI upset, constipation and fatigue. No patient reported skin changes. Visual symptoms had no reliable correlation with total cumulative dosing (range 9-281g). Ophthalmology consultations have been obtained for 21% (n=5) of patients, and none have retinal pigmentation changes. The majority of patients (n=20) decided to follow up at their regularly scheduled appointment. Immediate follow up was requested by four patients and 1 has requested to be taken off of EZG. For all who had not seen an ophthalmologist, a referral was placed or planned.Conclusions: Side effects were common in patients on EZG and led to discontinuation of the drug in about one third of patients. Four patients noted visual symptoms and one patient stopped the medication specifically because of decreased visual acuity. None of our patients has experienced skin changes. With vigilant monitoring, we may discover that these side effects are occurring sooner than the FDA warning states and/or are associated with a certain cumulative dose range. Data collection continues at routine follow-ups as a part of the development of a long-term safety protocol.