Search

Arne Reimers,1,2 Jon Andsnes Berg,3 Margrete Larsen Burns,4 Eylert Brodtkorb,5,6 Svein I Johannessen,6,7 Cecilie Johannessen Landmark4,7,8 1Department of Clinical Pharmacology, St Olavs University Hospital, Trondheim, Norway; 2Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 3Laboratory of Clinical Biochemistry, Section of Clinical Pharmacology, Haukeland University Hospital, Bergen, Norway; 4Department of Pharmacology, Section for Clinical Pharmacology, The National Center for Epilepsy, Oslo University Hospital, Oslo, Norway; 5Department of Neurology and Clinical Neurophysiology, St Olavs University Hospital, Trondheim, Norway; 6Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; 7The National Center for Epilepsy, Oslo University Hospital, Oslo, Norway; 8Programme for Pharmacy, Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway Background and objective: Laboratories sometimes use different reference ranges for the same antiepileptic drug (AED), particularly for new and poorly investigated drugs. This may contribute to misunderstandings, concerns or inappropriate dose changes, which in turn may affect therapeutic effect, drug safety or treatment adherence. Therefore, the Norwegian Association of Clinical Pharmacology wished to update and harmonize the reference ranges for AEDs and establish national guidelines for Norway. Methods: A working group collected information on the reference ranges used by Norwegian laboratories for all commonly used AEDs. These reference ranges were compared to recent recommendations by the International League Against Epilepsy, current literature, applicable clinical studies, reference ranges used by leading Northern European epilepsy centers outside of Norway, and routine data derived from Norwegian laboratory databases. Results: Reference ranges varied between laboratories for four of 23 available AEDs (lamotrigine, valproate, eslicarbazepine and oxcarbazepine). For four AEDs (brivaracetam, perampanel, stiripentol and sulthiame), reference ranges had not previously been established. In total, 13 reference ranges were either harmonized, updated or newly established. No changes were applied to the remaining 10 AEDs. Conclusion: Updated and harmonized reference ranges are now available for 22 of the 23 AEDs available in Norway. The exception is vigabatrin (reference range not applicable). Revision of reference ranges is an important part of pharmacovigilance of AEDs and must be a continuous process based on current literature and clinical experience. Keywords: antiepileptic drug, serum concentration, reference range, therapeutic drug monitoring

Focal-onset seizures are manifestations of abnormal epileptic firing of brain cells in a localised area or areas of the brain. The diagnosis of focal-onset seizures initially entails an EEG, a detailed history from the patient and eyewitnesses, as well as computer tomographic or, preferably, magnetic resonance imaging scans. Video EEG to record ictal events may be necessary to establish the correct diagnosis.Focal seizures are classified according to the International Classification of Epileptic Seizures and International Classification of Epilepsies and Epilepsy Syndromes. It is important to try to decide how the seizure event fits into this system in order to successfully evaluate and optimise treatment, as well as to give detailed information to the patient about their seizures and prognosis.Once the decision to treat the seizures has been made, the physician must choose which medication is the most appropriate to begin with. Carbamazepine, phenytoin or valproic acid (sodium valproate) are often rated as first-line drugs, but factors such as adverse-effect profiles, age, possibility of pregnancy, and concomitant diseases and medication also need to be considered. Most of the newer antiepileptic drugs (AEDs) appear to have good efficacy and better tolerability than the older agents, but evidence to support their superiority is scarce and has led to conflicting advice in several guidelines. Among the newer AEDs, lamotrigine, gabapentin, topiramate and oxcarbazepine have obtained monotherapy indication in many countries. The higher costs of the newer AEDs may inhibit their wider use, especially in poorer countries. [ABSTRACT FROM AUTHOR]