Drug Interaction Report

Coadministration with inhibitors of CYP450 2C19 may theoretically increase the plasma concentrations of phenobarbital, which is a substrate of the isoenzyme. Some studies have reported an approximately 20% decrease in the total clearance of phenobarbital in individuals who are poor metabolizers of CYP450 2C19, although an interaction with specific CYP450 2C19 inhibitors has not been reported. Other studies have found no significant difference in the pharmacokinetics of phenobarbital amongst subjects with various CYP450 2C19 genotypes, which would suggest a minor role of CYP450 2C19 in the overall clearance of phenobarbital. No precautions appear to be necessary during coadministration of phenobarbital with CYP450 2C19 inhibitors. However, dosage adjustments may be necessary if an interaction is suspected.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.