Drug Interaction Report

MONITOR: Omeprazole may increase phenytoin serum concentrations and the risk of toxicity. The proposed mechanism is decreased clearance due to omeprazole-mediated inhibition of CYP450 2C19. Omeprazole may interact in a similar manner with other hydantoins. The clinical significance is unknown; however, higher omeprazole doses (more than 40 mg/day) may be more likely to interact.

MANAGEMENT: Clinical and laboratory monitoring may be appropriate whenever omeprazole is added to or withdrawn from therapy with phenytoin. Dosage adjustments may be considered if an interaction is suspected. Patients should be advised to notify their doctor if they experience symptoms of phenytoin toxicity (e.g., drowsiness, visual disturbances, change in mental status, seizures, nausea, or ataxia).

MONITOR: Rifampin and rifabutin may decrease plasma concentrations and effectiveness of hydantoins by inducing their CYP450 hepatic metabolism.

MANAGEMENT: Close observation for clinical and laboratory evidence of altered hydantoin effect is recommended. Patients should be advised to notify their physician if they experience loss of seizure control. Dosage should be increased as necessary.