Korean J Clin Pharm.  2024 Mar;34(1):71-78. 10.24304/kjcp.2024.34.1.71.

The Impact of Drug Interactions with Tyrosine Kinase Inhibitors on Adverse Event Development based on the changes of drug concentration level: Meta-analysis

• Hwang J
• Lee H

• KMID: 2564362
• DOI: http://doi.org/10.24304/kjcp.2024.34.1.71

Abstract

Background
Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience. However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA provides some guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted to understand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies.
Methods
A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators.
Results
Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone.
Conclusions
Study finds TKI-DDI not significantly linked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

Keyword

Antifungal agents; drug interactions; meta-analysis; tyrosine kinase inhibitors