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Drug-Drug Interaction Associated with Gastric Acid Inhibitor

[Speaker] Takahisa Furuta:1
1:Center for Clinical Research, Hamamatsu University School of Medicine, Japan

Many patients are taking a variety of medicines for the treatments of different kinds of disorders. PKs and PDs of some of medicines are often influenced by concomitant medicines, such as gastric acid inhibitors. Gastric acid inhibitors are often used with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents, such as low dose of aspirin and clopidogrel for the prevention of upper gastrointestinal bleeding. Patients with symptoms of heartburn and/or dyspepsia are sometimes treated with a gastric acid inhibitor. However, absorption of some drugs are decreased or increased by gastric acid inhibition. For examples, it is well known that gastric acid inhibitors inhibit the absorption of ketoconazole and that Cmax and bioavailability of ketoconazole is decreased. Gastric acid inhibitors also influence the absorption of some of molecular target agents.
Further more, some of acid inhibitors, such as proton pump inhibitor (PPI) and cimetidine, influence the hepatic metabolism of some medicines. It has been long discussed whether a PPI attenuates the antiplatelet function of clopidogrel to increase the risk of cardiovascular events of patients treated with clopidogrel. Recently, a new type of gastric acid inhibitor, vonoprazan, categorized to the potassium competitive acid blocker (P-CAB) has been clinically available. The gastric acid inhibition attained by vonoprazan is superior to PPIs, such as esomeprazole and rabeprazole. The eradication rates of H. pylori and cure rates of erosive esophagitis by vonoprazan-based regimens are superior to those of PPIs. However, we found that vonoprazan more potently attenuated the antiplatelet function of clopidogrel than esomeprazole. Interestingly, the influence of vonoprazan on the prasugrel appeared weaker than that on clopidogrel. Optimal selection of acid inhibitor should be performed by not only the need of the acid inhibitory effect but also the risk of drug-drug interaction with other medicines.

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