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. 2023 Feb 8;8(1):100880. doi: 10.1016/j.esmoop.2023.100880

Figure 1.

Figure 1

Proton pump inhibitor (PPI) interactions with anticancer drugs. Pemetrexed and methotrexate are excreted by renal transporters (hOAT3) inhibited by PPIs, resulting in higher risk of hematological toxicity.35, 36, 37 Inhibition of gastric H+K+ ATPase increases the gastric pH and reduces absorption of many anticancer drugs, particularly tyrosine kinase inhibitors (TKIs), capecitabine and cyclin-dependent kinase (CDK) 4/6 inhibitors.9,23,24,38,39,42,73,75 This increase in gastric pH also eliminates the crucial role in filtering out bacteria and with a direct role of PPIs on bacteria results in a dysbiose.26,27 This dysbiose in association with a direct action of PPIs on immune system may decrease or erase efficacy of immune checkpoint inhibitors and may interact with efficacy of anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and chimeric antigen receptor (CAR)-T cells.31,83,84,89 Colored boxes: drug–drug interactions with clinically demonstrated interactions; white boxes: suspected drug–drug interactions with clinically conflicting results.