Potential drug-drug interactions (DDIs) exist in breast cancer patients undergoing cyclin-dependent kinase (CDK) 4/6 inhibitors chemotherapy, suggests a study.
Furthermore, “the application of drug interaction detectors could facilitate additional implementation of research especially designed for interventions aimed at enhancing patient care,” the researchers said.
In this retrospective analysis (January 2017 to January 2023), the researchers used medical records to obtain the baseline characteristics of patients under CDK 4/6 chemotherapy. They further assessed the potential DDIs using drug interactions checker software, including Micromedex online database system, Drugs.com interaction checker, and UpToDate Lexicomp.
Seventy-five co-medications were prescribed along with palbociclib and ribociclib in this study. Potential drug interactions occurred in cancer patients treated with palbociclib and ribociclib combined with analgesics, statins, and acid-reducing medications. [J Oncol Pharm Pract 2026;doi:10.1177/10781552251314811]
Twenty-one patients were included in the analysis, of whom 17 (80.95 percent) were found to have potential DDIs. Of these 17 patients, 41.26 percent had major pharmacokinetic interactions, 42.85 percent had moderate ones, and 15.87 percent had pharmacodynamic interactions.
“The current investigation successfully determined the frequency and variables associated with probable DDIs mediated by P-glycoprotein (P-gp) and cytochrome P450 (CYP450) isozymes in the context of CDK 4/6 inhibitors chemotherapy,” the researchers said.
Drug interactions
The most common DDIs seen in this study involved the combination of amiodarone and palbociclib, affecting the CYP3A4 enzyme, and atorvastatin plus palbociclib/ribociclib, affecting the activity of P-gp transporter. The second most frequently prescribed medication was spironolactone. Many studies have shown the inhibitory effect of spironolactone on P-gp. [Heliyon 2022;8:e11278]
Furthermore, co-administration of digoxin and spironolactone results in increased plasma concentration of digoxin. [Eur J Clin Pharmacol 1992;42:481-485]
“It is important to acknowledge that a majority of these drugs are concurrently implicated in both CYP3A4 and P-gp pathways, thereby further increasing the unpredictability of the final outcome,” the researchers said.
Both palbociclib and ribociclib contain cardiotoxic effect with uncertain aetiology. Additionally, ribociclib has been shown to prolong the QT interval in an earlier study. [Front Oncol 2022;12:1-11]
“Regarding this matter, it has been observed that among the co-prescribed drugs, antibiotics, antimycotics, and antibacterials exhibit the greatest potential for pharmacodynamic interactions through the mechanism of QT prolongation,” the researchers said.
Limitation
The current study was limited by its small sample size. However, the findings still confirmed “the frequency, array, and variables associated with probable DDIs facilitated by P-gp and CYP3A4 in the context of CDK 4/6 inhibitors chemotherapy,” according to the researchers.
Drug interactions can affect the patient’s quality of life, and failure to identify these interactions can result in greater morbidity. “Hence, it is advisable to conduct a thorough assessment of potential drug interactions when administering medications for commonly occurring comorbidities, such as diabetes and hypertension,” the researchers said.
“Further investigation is necessary to comprehensively examine the impact of DDIs on adverse drug events and clinical outcomes, such as the comparison of hospitalization rates,” they added.