Phenytoin and enteral feedings: Does evidence support an interaction?

OBJECTIVE: To systematically review the reported interaction between oral d osage forms of phenytoin and enteral feeding formulations with respect to t he evidence supporting or refuting its existence, proposed mechanism(s) und erlying the interaction, and recommended interventions. DATA SOURCES: We conducted a MEDLINE search (1966-April 2000) for English-l anguage articles on phenytoin-enteral feeding interactions; the search term s used were phenytoin,enteral feeding, and/or interaction, and/or in vitro. This search was supplemented by a bibliographic review of all relevant art icles. STUDY SELECTION: Prospective, randomized, controlled studies; prospective, nonrandomized, controlled studies; prospective, nonrandomized, uncontrolled studies; retrospective studies clinical experience reports; case reports; in vitro studies; and letters ere evaluated for relevant information. DATA EXTRACTION: Data elements abstracted from these articles were study de sign, type (patients or healthy volunteers) and number of subjects involved , method of administration of phenytoin and enteral feeding, formulation of phenytoin, type of feeding (and whether it was continuous or interrupted), major findings, and proposed mechanisms of the interaction. DATA SYNTHESIS: Although four prospective, randomized, controlled trials in healthy human volunteers refute th existence of the interaction. there are numerous reports and studies showing dramatic decreases of serum phenytoin concentrations in patients when it is coadministered with enteral feeding formulations. Therefore, evidence supports the existence of this interactio n in patients and in vitro studies, but not in healthy volunteers. Unfortun ately, the exact mechanisms underlying this interaction remain unknown. Man y methods have been devised to prevent and treat the interaction once it ha s occurred; however, a single generally accepted, and practical interventio n strategy is still lacking. CONCLUSIONS: The exact role of enteral feeding in this interaction is uncle ar due to the lack of prospective, randomized, controlled trial performed i n patients. However, decreased serum phenytoin concentrations associated wi t enteral feeding may increase the risk of seizures. Clinicians should be a ware of this potential drug-nutrient interaction and design a patient-speci fic care plan that includes consideration of the enteral feeding formulatio n and method of administration, as well as the phenytoin dosage form, sched ule of administration, and monitoring.