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.

Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma

“…Alternative strategies that were not implemented at our institution include that of changing twice‐daily PPI regimens to once‐daily regimens, scheduling the PPI to be taken at the same time or 2 hours after the TKI, and adding acidic beverages to overcome this pharmacokinetic drug interaction. Van Leeuwen et al .…”

“…Alternative strategies that were not implemented at our institution include that of changing twice-daily PPI regimens to once-daily regimens, scheduling the PPI to be taken at the same time or 2 hours after the TKI, 7 and adding acidic beverages to overcome this pharmacokinetic drug interaction. Van Leeuwen et al 13 reported that in patients with nonsmall cell lung cancer who took erlotinib with the beverage cola while on esomeprazole, administering erlotinib with cola led to increased erlotinib bioavailability.…”

“…Both strategies can be challenging for patients who benefit from twice-daily ASM dosing regimens, and, even so, these strategies do not completely eliminate the interaction. 7 To date, there have been no studies in peer-reviewed literature assessing the effects of ASM and concomitant PAZ administration on STS survival outcomes. Other studies have evaluated the drug interaction of ASMs and TKIs with conflicting results.…”

“…Options include separating the administration of PAZ from the ASM or to reduce the dose of ASM. Both strategies can be challenging for patients who benefit from twice‐daily ASM dosing regimens, and, even so, these strategies do not completely eliminate the interaction …”

Appropriateness of proton pump inhibitor use in patients admitted under the general medical unit

“…A PPI‐induced increase in gastric pH has been shown to affect the pharmacokinetics and clinical efficacy of drugs such as tyrosine kinase inhibitors (e.g. ceritinib, dasatinib, erlotinib, gefitinib, lapatinib, nilotinib and pazopanib) and mycophenolate mofetil in transplant recipients . Patients on prolonged treatment with PPIs are at increased risk of severe hypomagnesaemia that sometimes requires hospitalisation .…”