Authors :
Presenting Author: Ilo Leppik, MD – University of Minnesota
allison vassar, RN – Healthpartners
Yuhan long, BS – Uniersity of Minnesota
rorry remmel, PhD – University of Minnesota
sima patel, MD – University of Minnesota
david hamley, RN – University of Minnesota
Angela Birnbaum, PhD – University of Minnesota
Rationale:
Rationale: Rufinamide (RUF) is an antiseizure medication approved for the treatment of seizures associated with Lennox-Gastaut syndrome . It is extensively metabolized , with the reaction is catalyzed mainly by carboxylesterases 1 and 2 with CES1, non-cytochrome P450 (CYP450) enzymes, with an elimination half-life of 8-12 hours. As metabolism is through non-P450 routes few drug interactions are expected. It came to our attention that some patients receiving RUF developed similar adverse events (AEs) after undergoing procedures requiring general anesthesia. The objective of this study was to identify patients who were receiving RUF and experienced adverse events (AEs) after a surgical procedure to characterize the relationship with drug blood concentrations.
Methods:
Methods: The EPIC data base of the Fairview U of MN system was reviewed to identify persons prescribed RUF and who had surgery requiring general anesthesia over a multiyear period ending 5/21/2025. Demographic data, occurrence of AEs, and RUF doses and blood concentrations were extracted.
Results:
Results: A total of 216 persons prescribed RUF were identified, ages 4 to 68 years. Of these, 29 had undergone 30 procedures requiring general anesthesia. 17 were females 12 males, and more than half had a diagnosis of Lennox-Gastaut syndrome. Overall, 15 (50%) uses of general anesthesia were associated with clinically significant AEs within days of the procedure. These were associated with marked increases in RUF concentrations from pre-surgical values. Seven patients had concentrations greater than 40 ug/ml (ARUP laboratory limit) and one laboratory reported ta level of 67.1 ug/ml (non-ARUP lab) from an earlier concentration of 9.6 ug/ml. The mean pre-anesthesia RUF level was 16.79 ug/ml (SD 4.6); post-surgery mean 39.72 (SD 9.18). The increase was 136.5% (p = 1.63x10-5). The most common AEs were vomiting, nausea, anorexia and weight loss. There was no difference in sex or age between those with no AEs and those with AEs. The last episode occurred 2/2025. Pre surgery RUF level during 1/25 was 9.7; 19 days post surgery level was obtained because of nausea, vomiting and lethargy, and was >40.0; 33 days post surgery 32.5, and 70 days post surgery 19.4.
Conclusions:
Conclusions: AEs were associated with elevated RUF. concentrations that persist for more than a month as the elimination of RUF is decreased. It is important to obtain baseline levels (personal therapeutic levels) when a person has attained their therapeutic
goal. 1Another level should be obtained a few days after surgery an if significantly elevated, a short period of dose reduction should be considered to avoid AEs.
1. Patsalos PN, Berry DJ, Bourgeois BFD, Cloyd JC, Glauser TA, Johannessen SI, Leppik IE, Tomson T, Perucca E. Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008 Jul;49(7):1239-1276.
Funding: Epilepsy Innovation Fund, University of Minnesota