Drug–drug interactions in targeted cancer therapies: a focus on tyrosine kinase inhibitors

This is the authors' abstract. We don't add key points for this paper.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have significantly improved outcomes for cancer patients. However, TKIs have a narrow therapeutic window, impact a high-risk population, and are frequently combined with additional medications, each of which increases the risk of drug-drug interactions (DDIs). As polypharmacy becomes more common, especially in older and higher-risk groups that are prescribed TKIs, there is an increased risk for harmful DDIs. AREAS COVERED: TKI-related DDIs can lead to toxicity or reduced efficacy, which worsens patient outcomes and quality of life. In this review, we utilized the Drug Interaction Database (DIDB), FDA labels, and PubMed TKI DDI/ADME queries to outline the mechanisms underlying both pharmacokinetic (PK) and pharmacodynamic (PD) DDIs with TKIs. Pharmacokinetic DDIs involve changes in the absorption, distribution, metabolism, and excretion (ADME) of a molecule (victim) caused by another drug (perpetrator). These DDIs may involve direct inhibition, post-translational modification, or transcriptional regulation. Pharmacodynamic DDIs involve overlapping mechanisms resulting in additive, synergistic, or antagonistic effects when two medications are combined. EXPERT OPINION: Understanding the mechanisms underlying DDIs facilitates a better grasp of TKI clinical pharmacology and will help in the development of strategies to optimize drug dosing and avoid DDIs.