Because of their effect on gastric acidity, PPIs can reduce the bioavailability of drugs that require a low pH for absorption, such as ampicillin, cyanocobalamin, digoxin, iron, or ketoconazole. The metabolism of omeprazole and lansoprazole by cytochrome P450 enzymes is another potential source of drug interactions. Omeprazole is involved with more drug interactions because of its greater activity at CYP2C19. It inhibits the metabolism of clarithromycin, benzodiazepines, phenytoin, and warfarin. The clinical significance of these reactions is highly variable among patients.
Lansoprazole inhibits the metabolism of theophylline.
Patients receiving any of these combinations should be closely monitored for signs of drug accumulation. The drug interaction between omeprazole and clarithromycin is unique. Each drug inhibits the metabolism of the other, resulting in increased serum concentrations of both agents. The result of this interaction may actually be beneficial to the patient during short-term therapy. The success of multidrug regimens to eradicate H. pylori may be due to the higher concentrations of the drugs achieved when given together.