Drug Interactions between amoxicillin / clarithromycin / omeprazole and cefpodoxime

GENERALLY AVOID: The coadministration with H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH may reduce the oral bioavailability of cefpodoxime proxetil and cefuroxime axetil. The proposed mechanism is a pH-dependent reduction in drug dissolution and absorption. In ten healthy volunteers, famotidine 40 mg administered one hour before the ingestion of cefpodoxime proxetil 200 mg led to an approximately 40% reduction in the cefpodoxime peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) compared to when the drug was given alone. Similar results were reported with ranitidine in another study, where cefpodoxime Cmax and AUC decreased by approximately 30%. Likewise, pretreatment with ranitidine plus sodium bicarbonate decreased the Cmax and AUC of cefuroxime by over 40% in six healthy volunteers. The clinical significance of these effects is unknown, but potentially reduced antibiotic efficacy should be considered.

MANAGEMENT: Until further data are available, patients treated with cefpodoxime proxetil or cefuroxime axetil may want to avoid using H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH. An alternative antibiotic may be considered if these medications cannot be discontinued.

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.