BACKGROUND: Previous studies evaluated the disposition of IV phenytoin loading doses and found that obese patients had increased drug distribution into excess body weight, larger volumes of distribution, and longer half-lives when compared to their nonobese counterparts. We assess the safety and efficacy of fosphenytoin loading doses in patients with different body mass indices (BMIs). METHODS: A retrospective chart review was conducted in 410 patients who received fosphenytoin. Patients were divided into 2 groups: BMI <30 (nonobese) and BMI ≥30 (obese). Patient demographics, fosphenytoin dose administered in mg/kg body weight, renal and liver function tests, fosphenytoin drug levels, and pre- and post-fosphenytoin administration vital signs were collected to assess for adverse events. Necessity of additional antiepileptic loading doses was used as a surrogate for clinical efficacy. RESULTS: The median dose of fosphenytoin administered was 19 mg/kg (interquartile range 15-20). The most frequently encountered adverse event was hypotension, which occurred in 39% of the cohort. Using a Bonferroni adjustment for multiple comparisons, there were no differences in adverse events between the 2 groups. The need for additional antiepileptic loading doses was not different between the 2 groups (p = 0.07). CONCLUSIONS: The incidence of adverse events and the need for repeat loading antiepileptic medications was similar between the 2 groups. From our findings, the patients in our study did not receive empiric loading dose adjustments and the current method of loading fosphenytoin achieves similar outcomes, regardless of the patient's BMI.
BACKGROUND: Previous studies evaluated the disposition of IV phenytoin loading doses and found that obese patients had increased drug distribution into excess body weight, larger volumes of distribution, and longer half-lives when compared to their nonobese counterparts. We assess the safety and efficacy of fosphenytoin loading doses in patients with different body mass indices (BMIs). METHODS: A retrospective chart review was conducted in 410 patients who received fosphenytoin. Patients were divided into 2 groups: BMI <30 (nonobese) and BMI ≥30 (obese). Patient demographics, fosphenytoin dose administered in mg/kg body weight, renal and liver function tests, fosphenytoin drug levels, and pre- and post-fosphenytoin administration vital signs were collected to assess for adverse events. Necessity of additional antiepileptic loading doses was used as a surrogate for clinical efficacy. RESULTS: The median dose of fosphenytoin administered was 19 mg/kg (interquartile range 15-20). The most frequently encountered adverse event was hypotension, which occurred in 39% of the cohort. Using a Bonferroni adjustment for multiple comparisons, there were no differences in adverse events between the 2 groups. The need for additional antiepileptic loading doses was not different between the 2 groups (p = 0.07). CONCLUSIONS: The incidence of adverse events and the need for repeat loading antiepileptic medications was similar between the 2 groups. From our findings, the patients in our study did not receive empiric loading dose adjustments and the current method of loading fosphenytoin achieves similar outcomes, regardless of the patient's BMI.
Authors: Catherijne A J Knibbe; Margreke J E Brill; Anne van Rongen; Jeroen Diepstraten; Piet Hein van der Graaf; Meindert Danhof Journal: Annu Rev Pharmacol Toxicol Date: 2014-10-17 Impact factor: 13.820
Authors: Stuart P Swadron; Maria I Rudis; Kian Azimian; Paul Beringer; Diana Fort; Michael Orlinsky Journal: Acad Emerg Med Date: 2004-03 Impact factor: 3.451
Authors: Abhishek G Sathe; Jordan J Elm; James C Cloyd; James M Chamberlain; Robert Silbergleit; Jaideep Kapur; Hannah R Cock; Nathan B Fountain; Shlomo Shinnar; Daniel H Lowenstein; Robin A Conwit; Thomas P Bleck; Lisa D Coles Journal: Epilepsia Date: 2020-05-18 Impact factor: 6.740