Interaction of Nasogastric Phenytoin and Enteral Feeding Solution

Abstract

To the Editor: — Drug interactions are of great concern to geriatricians. Phenytoin, the most commonly prescribed antiepileptic, interacts with a wide variety of medications. We wish to draw attention to the interaction between phenytoin and enteral feeding preparations such as Ensure and Osmolite, since the simultaneous use of phenytoin and enteral formulae is not uncommon. We report a case of an elderly woman whose serum phenytoin level was markedly depressed during concomitant administration of Osmolite. An 80-year-old woman was hospitalized with a right hemispheric cerebral infarct. Examination demonstrated stupor and a left hemiparesis. An EEG revealed status epilepticus and she received intravenous loading of phenytoin followed by a maintenance dose of 400 mg daily through a nasogastric tube, resulting in a serum level of 18.7 mcg/mL (therapeutic: 10–20 mcg/mL). Her mental status improved. Due to poor oral intake, Osmolite feeding via nasogastric rube at 50 cc/hr was begun on the sixth hospital day. Over the next four days, this was increased to 100 cc/hr for 16 hours a day. On the tenth day, the serum phenytoin level was 9.3 mcg/mL. A new loading dose of 800 mg phenytoin was given via the tube in two portions and the daily dose was increased to 500 mg. On the 12th day, the phenytoin level was 5 mcg/mL. The patient received 1000 mg orally in two portions but only had a level of 9.8 mcg/mL the next morning. On the 13th and 14th hospital days, she received 500 mg of phenytoin daily. Simultaneously, her Osmolite was discontinued and a pureed diet begun. On the 25th day, the serum phenytoin level was 13.3 mcg/mL and remained in therapeutic range thereafter without further dosage alterations. The patient was receiving no medications known to depress phenytoin levels. Phenytoin has a narrow therapeutic index. One reason for the difficulty in maintaining therapeutic levels may be an interaction between orally administered phenytoin and enteral feeding preparations. This was first noted by Baur1 in young head trauma patients whose phenytoin dose requirement plummeted when enteral feedings were discontinued. A postulated mechanism for this interaction is binding of phenytoin to calcium caseinate or magnesium present in complete diet formulae, rendering the drug unavailable for absorbtion.2 Hypoalbuminemia, frequently seen in patients who receive enteral formulae, can lead to a decline in total serum phenytoin levels but does not explain this apparent drug-nutrient interaction, as a similar decline in serum phenytoin levels has been noted in patients with normal albumin.3 No data exist as to the incidence of this drug-nutrient interaction. A review of common reference sources failed to reveal mention of the interaction. There are a few case reports.3–5 The interaction is clearly important, since subtherapeutic levels may result during enteral feeding and toxic levels may appear after withdrawal. Monitoring of serum levels and alert adjustment in dosage are necessary.