Changes in drug load during lacosamide combination therapy: A noninterventional, observational study in German and Austrian clinical practice

Abstract

Introduction Effects of antiepileptic drug (AED) load changes in patients with focal seizures have not been well evaluated. Methods SP1065 (NCT01673282) was a noninterventional, prospective, observational study conducted in a clinical practice setting. Patients (aged ≥18 years) with focal seizures were enrolled within 7 days of being prescribed adjunctive lacosamide. Observation period was ~6 months. Drug load was assessed using percentage change in ratio of actual prescribed dose and World Health Organization defined daily dose (DDD) for concomitant AEDs and all AEDs (including lacosamide). Subgroups were defined for patients with at least one concomitant sodium channel–blocking AED (SCB [+]) and those without (SCB [−]). Results A total of 311 patients were assessed for safety, 302 for measurement of drug load, and 240 for effectiveness. Ratio of AED dose to DDD decreased for concomitant AEDs (−9.6%) and increased for all AEDs (including lacosamide; 15.5%). Median reduction in focal seizure frequency per 28 days was 100% (range: −100, 2275.8). 70.4% and 61.7% of patients had a ≥50% or ≥75% reduction in seizure frequency, respectively; 50.8% became seizure‐free. In the SCB (+) subgroup (n = 149), ratio of AED dose to DDD decreased for concomitant AEDs (−15.0%) and increased for all AEDs (10.7%). In the SCB (−) subgroup (n = 153), ratio of AED dose to DDD decreased for concomitant AEDs (−4.4%) and increased for all AEDs (20.2%). Fifty‐seven patients (18.3%) reported ADRs, most commonly dose >400 mg/d (7.1%). Seventeen patients (5.5%) had ADRs leading to discontinuation. Significance Addition of lacosamide resulted in reduction of concomitant AED drug load regardless of whether concomitant AEDs were SCB (+) or SCB (−). These results indicate that addition of lacosamide in patients with focal seizures could allow clinicians to withdraw or reduce the dose of less well‐tolerated or less effective AEDs.

A prospective, multicenter, noninterventional study in Taiwan to evaluate the safety and tolerability of lacosamide as adjunctive therapy for epilepsy in clinical practice

“…The overall incidence of TEAEs (55.6%) was within the range reported in observational and noninterventional studies of adjunctive LCM (19.9-73.8%) [5][6][7][8]. Incidence was lower than that reported in a pooled analysis of data from three pivotal trials of adjunctive LCM in mainly Caucasian patients (81.0% for all LCM dosage groups, 69.6% for 200 mg/day, 82.2% for 400 mg/day, and 93.6% for 600 mg/day) [9] and in a randomized controlled trial of adjunctive LCM in Chinese and Japanese patients (72.2% for all LCM dosages, 65.0% for 200 mg/day and 79.4% for 400 mg/day) [10], despite a longer treatment period of approximately 1 year (vs 16-18 weeks).…”

Safety and Efficacy of Cenobamate for the Treatment of Focal Seizures in Older Patients: Post Hoc Analysis of a Phase III, Multicenter, Open-Label Study

“…Drug load is a method of measuring ASM burden that includes the total doses as well as the number of ASMs a patient is taking. For each drug in a patient’s regimen, the ratio of the actual patient’s ASM dose per day to the drug’s defined daily dose (DDD), a standardized daily maintenance dose provided by the World Health Organization, was calculated [ 20 ]. For instance, if a patient was receiving levetiracetam 1500 mg twice daily, their drug load would be the actual daily dose of levetiracetam (3000 mg/day) over the DDD for levetiracetam, which is listed as 1500 mg/day.…”

Клінічні Особливості Лікування Фокальної Резистентної Епілепсії

“…Зміни лікарського навантаження під час комбінованої терапії лакосамідом вивчались в неінтервенційному обсерваційному дослідженні в німецькій і австрійській клінічній практиці [17]. Загалом 311 пацієнтів оцінювали на безпеку, 302 -на вимірювання лікарського навантаження і 240 -на ефективність.…”