SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Neuropharmacology
Optimizing Phenytoin Therapy: A Systematic Review of Clinically Relevant Food and Herb Interactions
Provisionally accepted
ADRIANA MONSERRATH ORELLANA PAUCAR1*
Erick Thomas Mosquera-Lopez1Nancy Michelle Bustamante-Alvarez1María Gabriela Machado-Orellana1Daniela Alejandra Vintimilla-Rojas1John Diego Atiencia-Palacios2
Ana Cristina Espinoza Fajardo1- 1University of Cuenca, Cuenca, Ecuador
- 2Ministerio de Salud Publica de Ecuador, Quito, Ecuador
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Phenytoin, a widely prescribed anticonvulsant, presents clinical challenges due to its narrow therapeutic index and potential interactions with various foods, herbs, and medications. These interactions can lead to adverse effects or subtherapeutic responses, necessitating a thorough understanding by healthcare professionals to optimize patient care. This systematic review investigates clinically significant interactions between phenytoin and dietary components. A comprehensive search across PubMed, Scopus, and the Health Virtual Library identified relevant studies published from January 1960 to December 2024. Data extraction utilized standardized forms, and evidence certainty was evaluated using the GRADE criteria. Twelve of the 826 initially identified articles met the inclusion criteria. Findings revealed diverse interactions: three articles reported no interaction, five indicated enhanced drug absorption, and one noted improved drug effectiveness. Conversely, three studies documented reduced efficacy due to interactions with specific foods or herbs. The review suggests that co-administration of phenytoin with folic acid may prevent deficiency without affecting plasma concentrations or drug efficacy. Concurrent use of phenytoin and piperine should be monitored due to potential absorption and increases in plasma levels. Additionally, it is suggested that the combination of noni and phenytoin be avoided, as it may reduce phenytoin concentrations to subtherapeutic levels. While these findings are based on studies of moderate evidence quality, further controlled clinical trials are necessary to refine pharmacological recommendations.
Keywords: Food-drug interaction, Nutrient-drug interaction, herb-drug interaction, Pharmacological interaction, Epilepsy, Phenytoin, Folic Acid
Received: 30 Jul 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 MONSERRATH ORELLANA PAUCAR, Mosquera-Lopez, Bustamante-Alvarez, Machado-Orellana, Vintimilla-Rojas, Atiencia-Palacios and Espinoza Fajardo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: ADRIANA MONSERRATH ORELLANA PAUCAR
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