Reference ranges for antiepileptic drugs revisited: a practical approach to establish national guidelines

• Published in: Drug design, development and therapy Vol. 12; pp. 271 - 280
• Main Authors: Reimers, Arne, Berg, Jon Andsnes, Burns, Margrete Larsen, Brodtkorb, Eylert, Johannessen, Svein I, Johannessen Landmark, Cecilie
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Anticonvulsants; Anticonvulsants - blood; Antiepileptic agents; Antiepileptic drug; Associations; Clinical Laboratory Techniques - standards; Clinical trials; Consensus; Dosage and administration; Drug dosages; Drug Monitoring - standards; Drugs; Epilepsy; Evaluation; Guidelines; Hospitals; Humans; Laboratories; Lamotrigine; Medical research; Monkeys & apes; Norway; Original Research; Oxcarbazepine; Patient care; Patient compliance; Perampanel; Pharmacology; Pharmacovigilance; Practice guidelines (Medicine); Practice Guidelines as Topic - standards; reference range; Reference Values; Safety and security measures; serum concentration; Stiripentol; Sulthiame; therapeutic drug monitoring; Valproic acid; Vigabatrin; Working groups; Norway; serum concentration; reference range; antiepileptic drug; therapeutic drug monitoring
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/dddt.s154388

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. 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. 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. 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.