Prescription Behaviour and Drug Interactions of Acid Suppressants With Tyrosine Kinase Inhibitors in Patients With Leukaemia: Data From Germany.

BACKGROUND

Tyrosine kinase inhibitors (TKIs) are essential in treating chronic myeloid leukaemia (CML) and other malignancies. Their absorption, however, is highly pH-dependent, making them susceptible to interactions with acid-suppressing agents such as proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs) and antacids. Despite clear warnings, real-world data show frequent co-administration, which may compromise therapeutic efficacy.

METHODS

This study combines two approaches-(1) a systematic review summarizing the impact of acid suppressants on TKI pharmacokinetics and clinical outcomes, and (2) an analysis of German prescription data from the Insight Health co-prescription database, focusing on TKIs primarily used for CML.

RESULTS

Results indicate substantial co-prescription rates involving dasatinib, nilotinib, imatinib, bosutinib and ponatinib, with variations across years and agents. Pharmacokinetic evidence demonstrates that PPIs and H2RAs can significantly reduce systemic TKI exposure, with reported decreases of up to 96% in peak plasma concentration and 88% in overall exposure. These reductions have been associated with poorer clinical outcomes, including decreased survival.

CONCLUSION

The findings highlight the need for improved prescriber awareness, adherence to guidelines and risk mitigation strategies such as therapeutic drug monitoring or alternative dosing. Collaborative efforts between clinicians and regulatory bodies are essential to minimize risks and optimize patient outcomes.