Drug Interaction of Proton-pump Inhibitors and Other Medicines

Proton-pump inhibitors (PPIs) are a class of medications for the treatment of heartburn and acid-related disorders. People should be aware of how proton pump inhibitors interact with other drugs they take. On one hand, Proton-pump Inhibitors have long-lasting acid suppression effect, and alter the pH of the stomach, on the other hand,  PPIs are mainly metabolized by CYP2C19 and CYP3A4 in the body, and have varying degrees of inhibitory effects on CYP2C19, CYP3A4, p-glycoprotein and other transporters. Below are medicines with drug interaction with Proton-pump Inhibitors.

Tyrosine kinase inhibitors (TKIs)

Mechanism of action:The dissolution of some TKIs is pH-dependent, and the combined use of PPIs may result in reduced absorption and reduced bioavailability by 35% to 47%.
Suggestion: It is recommended that gefitinib, dasatinib, and erlotinib be avoided in combination with PPIs if possible.


Mechanism of action:Different PPIs have different degrees of inhibition on CYP2C19, which participates in the metabolism of PPIs (except ilaprazole) and warfarin at the same time. So PPIs may interfere with the metabolism of warfarin and enhance its anticoagulation effect and bleeding risk,
Suggestion:Pay attention to monitor INR and prothrombin time when PPIs are used in combination with warfarin.


Mechanism of action: Omeprazole inhibits the activity of CYP2C19, resulting in an increase in the AUC value of cilostazol and its active metabolite by 26% and 69%.
Suggestion: When cilostazol is used in combination with omeprazole, the dose of cilostazol should be reduced to 50 mg once, twice a day.

Citalopram or escitalopram

Mechanism of action:Both omeprazole and esmeprazole can inhibit the activity of CYP2C19, resulting in an increase in the blood concentration of citalopram by 35.3% and 32.8%, and an increase in blood concentration of escitalopram by 93.9% and 81.8%.
Suggestion: When combined with omeprazole or esomeprazole, the maximum dose of citalopram is 20 mg a day, and the dose of escitalopram should be reduced by 50%.

Mycophenolate mofetil

Mechanism of action:PPIs increase the pH value in the stomach and reduce the absorption and bioavailability of mycophenolate mofetil, which may lead to acute rejection.
Suggestion: PPIs and mycophenolate mofetil should be used with caution. Enteric solvent-based mycophenolate mofetil can be used to reduce the influence of PPIs on its absorption.


Mechanism of action: PPIs may block the efflux of methotrexate, resulting in high doses of methotrexate and increase the toxicity.
Suggestion: Patients using high-dose methotrexate should consider temporarily discontinuing PPIs or using replacement therapy.

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