Evaluation of phenytoin loading doses in overweight patients using actual versus adjusted body weight

Kelli Keats; Rebecca Powell; Jody Rocker; Jennifer Waller; Lindsey Sellers Coppiano

doi:10.1016/j.yebeh.2022.108833

Evaluation of phenytoin loading doses in overweight patients using actual versus adjusted body weight

Epilepsy Behav. 2022 Sep:134:108833. doi: 10.1016/j.yebeh.2022.108833. Epub 2022 Jul 13.

Authors

Kelli Keats¹, Rebecca Powell², Jody Rocker³, Jennifer Waller⁴, Lindsey Sellers Coppiano³

Affiliations

¹ University of Georgia College of Pharmacy, Department of Clinical and Administrative Pharmacy, 914 New Bailie Street, HM-118, Augusta, GA 30912, United States; Augusta University Medical Center, Department of Pharmacy, 1120 15(th) Street, Augusta, GA 30912, United States. Electronic address: kkeats@augusta.edu.
² University of Georgia College of Pharmacy, Department of Clinical and Administrative Pharmacy, 914 New Bailie Street, HM-118, Augusta, GA 30912, United States; Augusta University Medical Center, Department of Pharmacy, 1120 15(th) Street, Augusta, GA 30912, United States.
³ Augusta University Medical Center, Department of Pharmacy, 1120 15(th) Street, Augusta, GA 30912, United States.
⁴ Department of Population Health Sciences, Augusta University, Augusta, GA United States.

PMID: 35839643
DOI: 10.1016/j.yebeh.2022.108833

Abstract

Background and objectives: The appropriate loading dose strategy for phenytoin/fosphenytoin in overweight patients is unknown. A small pharmacokinetic study indicated that overweight patients have a higher volume of distribution and potentially would benefit from using adjusted body weight (AdjBW) instead of actual body weight (ABW) to calculate the loading dose. The purpose of this study was to determine the optimal loading dose strategy of phenytoin in patients whose ABW is greater than 120% of their ideal body weight (IBW) using either ABW or AdjBW for calculation of the loading dose.

Methods: This was a single center, retrospective study which included patients who received a loading dose of phenytoin of at least 10 mg/kg based on ABW, had a phenytoin level drawn <6 h after the end of the dose, and weighed ≥120% of their IBW. Patients were excluded if they received intramuscular phenytoin or fosphenytoin or were prescribed phenytoin prior to the loading dose. Patients were divided into two groups, those who were dosed using their AdjBW versus those dosed using ABW. The primary outcome was achievement of therapeutic phenytoin level of 10-20 mcg/mL. Secondary outcomes included achievement of a subtherapeutic or supratherapeutic level.

Results: A total of 195 patients (128 in AdjBW group and 67 in ABW group) met criteria for inclusion. Patients in the AdjBW group weighed more (96.2 kg vs. 91.2 kg, p = 0.04) and received a lower dose in milligrams (1364 vs. 1760, p < 0.0001) and in mg/kg of ABW (14.2 vs. 19.3, p < 0.0001). The primary outcome was achieved in 74% of patients in the AdjBW group and 57% of patients in the ABW group (p = 0.02). Patients in the ABW group were more likely to have a supratherapeutic level (43% vs. 22%, p = 0.003), although adverse reactions did not differ between the groups.

Discussion: Patients weighing >120% of their IBW (average body mass index 33.5 kg/m²) who received a 20 mg/kg loading dose based on AdjBW were more likely to achieve a therapeutic phenytoin concentration compared to those dosed based on ABW. Further research is needed to correlate this finding with clinical outcomes, such as resolution of status epilepticus.

Keywords: Antiepileptic drugs; Epilepsy; Neurology; Obesity; Phenytoin; Status epilepticus.

MeSH terms

Body Mass Index
Body Weight
Humans
Overweight*
Phenytoin*
Retrospective Studies

Substances

Phenytoin