Serum Levels of Valproic Acid and Carbamazepine Do Not Correlate Well with End-Organ Dysfunction

Epilepsy Res. 2020 Jul:163:106343. doi: 10.1016/j.eplepsyres.2020.106343. Epub 2020 Apr 19.

Abstract

Background: Serum levels of anticonvulsants are commonly ordered; however, the clinical utility of these laboratory tests is unclear. Clarifying the significance of anticonvulsant drug levels is essential to allow physicians to make appropriate management decisions. We aimed to determine to what extent elevated serum levels of valproic acid (VPA) and carbamazepine (CBZ) correlate with laboratory indications of end-organ dysfunction.

Methods: We reviewed a consecutive sample of patients 0-18 years of age who, over a 2-year period, had at least one blood collection in which (1) serum [VPA] or [CBZ] was tested; and (2) at least one of the following tests was performed: alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelets, white blood cells (WBC), ammonia, sodium.

Results: 913 and 300 blood collections met criteria for VPA and CBZ, respectively. A slight increased frequency of having any abnormal laboratory value for elevated [VPA] compared to low/normal [VPA] was observed (p = 0.02; relative risk 1.27), while there was no difference in frequency of having any abnormal lab value for CBZ, nor were there significant differences for the individual lab values. When ALT and AST were plotted against [VPA] and [CBZ], no significant correlation was observed.

Conclusion: Serum [VPA] and [CBZ] are poor indicators of risk for drug-induced end-organ dysfunction. There are likely other, individualized risk factors that explain why certain patients develop adverse effects from these medications.

Keywords: Carbamazepine; Hyperammonemia; Leukopenia; Syndrome of inappropriate antidiuretic hormone secretion; Thrombocytopenia; Valproic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anticonvulsants / therapeutic use
  • Benzodiazepines / therapeutic use
  • Carbamazepine / therapeutic use
  • Child
  • Child, Preschool
  • Drug Therapy, Combination* / methods
  • Epilepsy / diet therapy*
  • Epilepsy / drug therapy
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Multiple Organ Failure / chemically induced*
  • Multiple Organ Failure / drug therapy
  • Valproic Acid / therapeutic use*

Substances

  • Anticonvulsants
  • Benzodiazepines
  • Carbamazepine
  • Valproic Acid