Drug Interactions between amoxicillin / clarithromycin / omeprazole and phenobarbital

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

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.