title: Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability.
abstract: Lacosamide (LCM) is a new antiepileptic drug (AED). Experience from therapeutic drug monitoring (TDM) in clinical practice is limited. The purpose of this study is to evaluate the pharmacokinetic variability of LCM in relation to efficacy and tolerability in patients with refractory epilepsy in a real-life setting. Variables included age, gender, daily doses and serum concentrations of LCM and other AEDs from the TDM-database at the National Center for Epilepsy in Norway. Clinical data regarding efficacy and tolerability were collected from medical records. The Norwegian Prescription Database (NorPD) was used to include population-based numbers of users. TDM-data from 344 patients were included. The median dose, serum concentration, and concentration/dose (C/D)-ratio of LCM was 350 (range 25-700) mg/day, 19.7 (range 8.1-56.2) µmol/L, and 0.06 (0.02-0.82) µmol/L/mg, respectively. Serum concentrations were reduced by 28% by concomitant use of enzyme inducers and increased by 30% in patients aged >65 years. Efficacy and tolerability were assessed in 227 patients: 29% had >50% seizure reduction (eight seizure free), 30% had no effect, and 44% reported adverse effects. In Norway, there were on average 500 patients per year using LCM in this period based on NorPD. The study demonstrated pharmacokinetic variability and use of TDM of LCM in Norway. Data were collected from multiple sources for improved pharmacovigilance. Serum concentrations were influenced by enzyme inducers and ageing, indicating the usefulness of TDM. Effect and tolerability were favorable within a suggested reference range of 10-40 µmol/L given drug-fasting conditions.
authors.affiliation: The National Center for Epilepsy, Oslo University Hospital, Sandvika, Oslo, Norway.|Department of Neurology, Innlandet Hospital Trust, Lillehammer, Norway.
authors.forename: Torleiv
authors.initials: T
authors.lastname: Svendsen
authors.affiliation: Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, Trondheim, Norway.|Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
authors.affiliation: Programme for Pharmacy, Department of Life Sciences and Health, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Pilestredet 50, 0167, Oslo, Norway.
authors.forename: Arton
authors.initials: A
authors.lastname: Baftiu
authors.affiliation: Section for Clinical Pharmacology, Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
authors.forename: Margrete Larsen
authors.initials: ML
authors.lastname: Burns
authors.affiliation: The National Center for Epilepsy, Oslo University Hospital, Sandvika, Oslo, Norway.|Programme for Pharmacy, Department of Life Sciences and Health, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Pilestredet 50, 0167, Oslo, Norway.
authors.forename: Svein I
authors.initials: SI
authors.lastname: Johannessen
authors.affiliation: The National Center for Epilepsy, Oslo University Hospital, Sandvika, Oslo, Norway. Cecilie.landmark@hioa.no.|Programme for Pharmacy, Department of Life Sciences and Health, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Pilestredet 50, 0167, Oslo, Norway. Cecilie.landmark@hioa.no.|Section for Clinical Pharmacology, Department of Pharmacology, Oslo University Hospital, Oslo, Norway. Cecilie.landmark@hioa.no.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Johannessen Landmark
mesh_terms: D000081:Acetamides / Q000097:blood* / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods; D000069279:Drug Resistant Epilepsy / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide
keywords: Antiepileptic drugs; Efficacy; Epilepsy; Lacosamide; Pharmacokinetic variability; Therapeutic drug monitoring; Tolerability