Drug Interactions between amoxicillin / clarithromycin / omeprazole and chloramphenicol

MONITOR: Chloramphenicol may inhibit the bactericidal effect of penicillins. Chloramphenicol acts by inhibiting cellular protein synthesis and can change actively growing bacteria into static ones. Since penicillins work by inhibiting cell wall synthesis, their effectiveness may be reduced. In addition, neurologic toxicity may be enhanced. Data have been conflicting, and no antagonism or synergistic effects have been reported.

MANAGEMENT: Until more information is available, this combination should probably be reserved for conditions where it has been found to be efficacious and avoided in situations where bactericidal activity is necessary, such as in bacterial meningitis or staphylococcal endocarditis. If the combination is necessary, some experts recommend administering the penicillin several hours before the chloramphenicol. Patients should be closely monitored for altered antimicrobial efficacy.

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.