Drug interactions between Dilantin and Phillips' Milk of Magnesia

ADJUST DOSING INTERVAL: Concurrent administration of antacids may decrease the bioavailability of phenytoin. The mechanism of interaction is unknown. In eight healthy volunteers, coadministration of a single 600 mg dose of phenytoin and an antacid containing either aluminum-magnesium hydroxide or calcium carbonate (dose equal to 160 mEq of neutralizing capacity) given one and three hours after meals and at bedtime on the same day resulted in an approximately 25% reduction in the total area under the concentration-time curve (AUC) of phenytoin compared to administration alone. An antacid containing aluminum hydroxide-magnesium trisilicate given in an equivalent dose also reduced the AUC of phenytoin, but the difference was not statistically significant. In another study, aluminum hydroxide-magnesium trisilicate caused a 12% reduction in steady-state serum phenytoin levels in six epileptic patients, but seizure frequency was not affected. There have also been isolated case reports of patients with low serum phenytoin levels or inadequate seizure control attributed to concurrent antacid administration. In a few of the patients, serum phenytoin levels rose two to threefold when antacid administration was delayed by 2 to 3 hours. However, some studies have failed to find a significant interaction with these antacids.

MANAGEMENT: Given the narrow therapeutic index and the large interindividual variability in the pharmacokinetics of phenytoin, patients requiring concomitant antacid therapy should consider separating the times of administration by at least two to three hours if possible. Serum phenytoin levels and seizure activity should be monitored.