Relative Bioavailability of Orally Administered Fosphenytoin Sodium Injection Compared with Phenytoin Sodium Injection in Healthy Volunteers

Kaucher, Kevin A.; Acquisto, Nicole M.; Rao, Gauri G.; Kaufman, David; Huntress, Jeff; Forrest, Alan; Haas, Curtis E.

doi:10.1002/phar.1589

Cited by 5 publications

(2 citation statements)

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“…[9][10][11] Despite the mechanistic uncertainty, many institutions have implemented practices to mitigate the phenytoin-feeding interaction, including dose increasing to account for lower bioavailability, routinely holding EN for administration, continuation of IV dosing until the patient no longer requires continuous EN, or using alternative dosage forms, such as administering IV fosphenytoin via the feeding tube. [12][13][14] At our institution, the decision to routinely hold EN to administer phenytoin was made because of the risk of rebounding phenytoin concentrations after EN is discontinued. With this strategy, however, comes the risk of underfeeding and hypoglycemia because of potential gaps in continuous feeding.…”

Section: Discussionmentioning

confidence: 99%

“…Although the precise mechanism underpinning this interaction has yet to be elucidated, it is believed to be related to the binding of phenytoin to the protein or calcium content of EN or phenytoin directly binding to the material of the gastric tube itself 9–11 . Despite the mechanistic uncertainty, many institutions have implemented practices to mitigate the phenytoin‐feeding interaction, including dose increasing to account for lower bioavailability, routinely holding EN for administration, continuation of IV dosing until the patient no longer requires continuous EN, or using alternative dosage forms, such as administering IV fosphenytoin via the feeding tube 12–14 …”

Section: Discussionmentioning

confidence: 99%

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Impact of an enteral nutrition holding guideline on daily nutrition goals in patients taking phenytoin

et al. 2023

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BackgroundConcomitant administration of enteral nutrition (EN) and phenytoin decreases phenytoin absorption. Concerns over impaired nutrition, however, may prevent EN from being held surrounding phenytoin administration. This study aimed to evaluate whether EN holding guidelines impacted nutrition goal achievement in patients taking phenytoin.MethodsAdult patients administered enteral phenytoin for acute or chronic seizures while receiving EN during a neurocritical care admission 6 months before and after EN holding guideline implementation were eligible. Patients without phenytoin concentrations or a clinical registered dietitian assessment were excluded. The primary outcome was the percentage of nutrition daily goals attained before and after implementation. Secondary end points included the incidence of hypoglycemia, differences in measured phenytoin concentrations, and rates of therapeutic (10–20 mcg/ml) and high‐therapeutic (15–20 mcg/ml) concentration attainment. Concentrations were adjusted for hypoalbuminemia using the Winter‐Tozer equation.ResultsFifty‐five patients representing 412 patient days and 1110 phenytoin administrations were included with 29 preimplementation and 26 postimplementation patients. Median percent attainment of daily EN goals was consistent preimplementation and postimplementation (86% vs 83%, P = 0.48). No significant change in rates of days with hypoglycemia was observed. Adjusted phenytoin concentrations were similar before and after implementation (14.1 vs 15.2 mcg/ml, P = 0.45), but the preimplementation cohort had a lower proportion of high‐therapeutic concentrations (23% vs 36%, P = 0.018).ConclusionHolding EN for phenytoin did not impact attainment of daily nutrition goals and was not associated with increased rates of hypoglycemia. This is the first study to evaluate the effect of EN holding on nutrition goals in patients receiving phenytoin.

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