Interactions
Important drug interactions are rare.[39][40] However, the most significant major drug interaction concern is the decreased activation of clopidogrel when taken together with omeprazole.[41] Although still controversial,[42] this may increase the risk of stroke or heart attack in people taking clopidogrel to prevent these events.
This interaction is possible because omeprazole is an inhibitor of the enzymes CYP2C19 and CYP3A4.[43] Clopidogrel is an inactive prodrug that partially depends on CYP2C19 for conversion to its active form. Inhibition of CYP2C19 may block the activation of clopidogrel, which could reduce its effects.[44][45]
Almost all benzodiazepines are metabolised by the CYP3A4 and CYP2D6 pathways, and inhibition of these enzymes results in a higher area under the curve (i.e., the total effect over time of a given dose). Other examples of drugs dependent on CYP3A4 for their metabolism are escitalopram,[46] warfarin,[47] oxycodone, tramadol, and oxymorphone. The concentrations of these drugs may increase if they are used concomitantly with omeprazole.[48]
Omeprazole is also a competitive inhibitor of p-glycoprotein, as are other PPIs.[49]
Drugs that depend on an acidic stomach environment (such as ketoconazole or atazanavir) may be poorly absorbed, whereas acid-labile antibiotics (such as erythromycin which is a very strong CYP3A4 inhibitor) may be absorbed to a greater extent than normal due to the more alkaline environment of the stomach.[48]
St. John's wort (Hypericum perforatum) and Ginkgo biloba significantly reduce plasma concentrations of omeprazole through induction of CYP3A4 and CYP2C19.[50]
