Treatment-emergent adverse events and antiseizure medication actual drug load

Tiffany Prétat; Irene Aícua-Rapún; Pascal André; Sebastien Lebon; Andrea O Rossetti; Laurent A Decosterd; Thierry Buclin; Jan Novy

doi:10.1016/j.yebeh.2022.108980

Treatment-emergent adverse events and antiseizure medication actual drug load

Epilepsy Behav. 2022 Dec;137(Pt A):108980. doi: 10.1016/j.yebeh.2022.108980. Epub 2022 Nov 11.

Authors

Tiffany Prétat¹, Irene Aícua-Rapún², Pascal André³, Sebastien Lebon⁴, Andrea O Rossetti⁵, Laurent A Decosterd⁶, Thierry Buclin³, Jan Novy⁷

Affiliations

¹ University of Lausanne, Lausanne, Switzerland.
² Department of Clinical Neurosciences, Neurology Service, Lausanne University Hospital (CHUV) and University of Lausanne, Switzerland; Spitalzentrum Biel, Switzerland.
³ Service of Clinical Pharmacology, Lausanne University Hospital (CHUV) and University of Lausanne, Switzerland.
⁴ Unit of Pediatric Neurology and Pediatric Neurorehabilitation, Woman-Mother-Child Department, Lausanne University Hospital CHUV, Switzerland.
⁵ Department of Clinical Neurosciences, Neurology Service, Lausanne University Hospital (CHUV) and University of Lausanne, Switzerland.
⁶ Laboratory of Clinical Pharmacology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
⁷ Department of Clinical Neurosciences, Neurology Service, Lausanne University Hospital (CHUV) and University of Lausanne, Switzerland. Electronic address: jan.novy@chuv.ch.

PMID: 36375306
DOI: 10.1016/j.yebeh.2022.108980

Abstract

Objective: The correlation between treatment-emergent adverse events (TEAE) and antiseizure medication (ASM) drug load is a controversial topic. Previous studies used daily defined dosage (DDD) to measure drug load. We aim to assess if ASM adjusted to body weight and plasma levels were associated with TEAE.

Methods: We analyzed clinical visits of a trial on therapeutic drug monitoring in outpatients with epilepsy. TEAE, treatment, and its changes, as well as ASM plasma levels, were recorded at each visit. Each medication level was stratified according to its position in relation to its proposed reference range (below, in the lower half, upper half, or above).

Results: We analyzed 424 visits (151 participants). Treatment-emergent adverse events were reported in 84 (20%) visits. There was no significant difference when comparing visits with TEAE with those without TEAE in terms of ASM drug load (calculated with DDD), corrected for body weight, their changes since the last visit, as well as summed plasma levels compared to reference ranges.

Significance: Actual drug load seems not to represent a major determinant of TEAE recorded during routine visits, even when accounting thoroughly for the patient's exposure to the treatment. The use of structured questionnaires and neuropsychometric tests may assess more accurately the potential consequences of drug loads.

Keywords: Adverse events; Antiepileptic drug; Antiseizure drug; Tolerability; Treatment discontinuation.

MeSH terms

Body Weight
Clinical Trials as Topic
Epilepsy* / drug therapy
Humans