Frequency of Clinically Relevant Drug–Drug Interactions Between Tyrosine Kinase Inhibitors and Proton Pump Inhibitors in Patients With Cancer Using Real‐World Data

BACKGROUND: Proton pump inhibitors (PPIs) raise stomach pH, leading to reduced bioavailability of many tyrosine kinase inhibitors (TKIs), thereby affecting treatment outcomes. To what extent this interaction occurs in clinical practice remains underexplored. OBJECTIVE: To determine the frequency of clinically relevant interactions between TKIs and PPIs in clinical practice and the duration of concomitant prescription. METHODS: A retrospective observational study was performed using the IADB.nl prescription database. Clinically relevant drug-drug interactions between TKIs and PPIs were assessed using four drug compendia (i.e., KNMP Kennisbank, Health Base, Lexidrug and Merative Micromedex). Patients who were prescribed a TKI and PPI with a clinically relevant DDI concomitantly, between 1 January 2013 and 31 December 2024, were included. Concomitant prescription was defined as ≥ 7 days of simultaneous prescription. FINDINGS: In total, 60 TKIs were registered in the Netherlands; 19 TKIs had clinically relevant interactions reported by at least one compendium. Overall, 393 of 1759 (22.3%) TKI users had a clinically relevant interaction. The median duration of concomitant prescription was 43 days (IQR = 81), with 91.1% of episodes lasting at least 30 days. CONCLUSION: PPIs and TKIs are frequently prescribed concomitantly in clinical practice. Prescribers should be more cautious when co-prescribing PPIs with TKIs and adapt the dosing regimens when appropriate.