Potentially Hazardous Drug-Drug Interactions Associated With Oral Antineoplastic Agents Prescribed in Chinese Tertiary Care Teaching Hospital Settings: A Multicenter Cross-Sectional Study

Abstract

Background: Oral administration increases the risk of interactions, because most oral antineoplastic agents (OAAs) are taken on a daily basis. Interactions can increase exposure to antitumoral agents or cause treatment failure. Potential drug–drug interactions (DDIs) are commonly observed in patients with cancer, while the extent to which OAAs related hazardous DDIs remains unclear.Methods: We studied the contraindication patterns between oral antineoplastic agents and other medications among cancer patients in two tertiary care teaching hospitals in China. A total of 20 clinically significant hazardous DDI pairs that involved 30 OAAs were identified based on the predetermined criteria. Patient medications were checked for DDIs by using the US Food and Drug Administration approved labeling. Descriptive statistics and uni- and multivariate logistic regression analyses were carried out.Results: In this study, 13,917 patients were included and a total of 297 DDIs were identified. The results revealed that proton pump inhibitors (PPIs), dexamethasone and fluoroquinolones were the most often involved hazardous DDIs with OAAs. The most prevalent contraindication is the simultaneous use of certain molecular targeted agents and PPIs. In the result of the multivariate analysis, younger age (0–20 group), increasing number of drugs and patient treated with targeted therapy had a higher risk for DDIs.Conclusion: The prevalence of OAAs related hazardous DDIs appears to be low in the cancer patients. However, physicians and clinical pharmacologists should be aware of the potential hazardous DDIs when prescribing OAAs, especially certain pH-dependent molecular targeted agents and potential QTc prolonging drugs.

Drug–Drug Interactions Involving Dexamethasone in Clinical Practice: Myth or Reality?

“…A study of potential DDI with imatinib, performed in 544 French patients with at least one prescription of imatinib, a substrate and inhibitor of CYP3A4, revealed that dexamethasone, which was prescribed in as much as 23% of patients, was the third potentially interacting agent involved (after Paracetamol and proton pump inhibitors), leading to specific recommendations to prescribers [12]. This is consistent with a Chinese study on potential DDI with every oral antineoplastic agent (13.917 patients), which found interaction between these oral chemotherapies and dexamethasone in 117 patients (39% of every registered DDI in this study) [13]. Nevertheless, the real impact of such DDI with dexamethasone remains poorly defined, as shown in a recent review of six databases of DDI between COVID-19 treatments and, respectively, cardiovascular and antidiabetic agents, where dexamethasone was described as a "moderate risk of DDI which requires caution and close monitoring" with all 19 anti-diabetic, anti-hypertensive and cardiovascular system-acting agents screened in this study [14].…”

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

“…2) Although, according to previous study report, over 40% of patients experienced adverse effects caused by DDI with oral cancer therapies such as TKIs, clinical practice only relying on person experience with scarcity of guidance. 6) Still, FDA provides guidance for DDIs in clinical aspects during drug development, which did not provide detailed explanations of DDIs between investigational drugs and concomitant medication based on specific drugs. 7) However, only the guideline indicates sponsors should assess the DDI potential before investigational drug administered with concomitant medications such as antifungal agents to patients.…”