Tyrosine Kinase Inhibitors and Proton Pump Inhibitors: An Evaluation of Treatment Options

Abstract

Tyrosine kinase inhibitors (TKIs) have rapidly become an established factor in oncology, and have been shown to be effective in a wide variety of solid and hematologic malignancies. Use of the oral administration route of TKIs offers flexibility and is convenient for the patient; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. Acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may subsequently decrease TKI solubility, bioavailability, and treatment efficacy. Clear and practical advice on how to manage PPI use during TKI therapy is currently not available in the literature. Since PPIs are extensively used during TKI therapy, prescribers are presented with a big dilemma as to whether or not to continue the combined treatment, resulting in patients possibly being deprived of optimal therapy. When all pharmacological characteristics and data of either TKIs and PPIs are considered, practical and safe advice on how to manage this drug combination can be given.

Fig. 1

Schematic 24-h intragastric pH curve during PPI use (enteric-coated, once daily) with delayed onset of action (3–4 h), duration of action (12–14 h with once-daily use) and the nocturnal duodenogastric reflux peak (obtained by the supine position during sleep). Derived from Hunfeld et al. [16], with permission. *Based on in vitro preclinical studies only. TKI tyrosine kinase inhibitor, PPI proton pump inhibitor