Conflicting meal recommendations for oral oncology drugs: pose risks to patient care?

• Published in: European journal of clinical pharmacology 2018-06, Vol.74 (6), p.833-842
• Main Authors: Yu, Guo, Wu, Dan-Na, Gong, Yan, Li, Guo-Fu, Zhou, Hong-Hao
• Format: Article
• Language: English
• Subjects: Antineoplastic drugs; Antitumor agents; Biomedical and Life Sciences; Biomedicine; Cancer; Clinical decision making; Clinical trials; Decision making; Drug dosages; Drug interaction; Drug interactions; Food; Meals; Oral administration; Patient compliance; Patients; Pharmacokinetics; Pharmacology/Toxicology; Point of View; Quality of life; Regulatory agencies; Schedules
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-018-2439-z

Purpose The labeling information, authorized by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), is expected to guide the method of drug administration with reference to meal intake, aiming at ensuring favorable safety profile and achieving optimal drug exposure. However, interactions between meals and a specific oral anticancer medication are complicated in that could be strongly affected by inter-individual variability in pharmacokinetics, meal compositions, and the timing of drug administration with respect to meal intake, which could lead to conflicting meal recommendations between regulatory authorities. The primary objective of this article was to systemically identify the conflicting food recommendations for oral antineoplastic drugs and explore the potential risks associated with these conflicting recommendations to patient-centered care. Methods We revisited, compared, and analyzed systemically the publicly accessible regulatory documents of the orally administered, anticancer drugs from the FDA and the EMA. Results After revisiting the labeling information and other regulatory documents of 43 oral oncology agents authorized by FDA during 2010–2016 and by the EMA at the time of this analysis finalized (December 2017), conflicting or inconsistent meal recommendations between the EMA and FDA were identified in 14% (6 of 43) oral anticancer drugs. Conclusion Conflicting food recommendations between regulatory authorities could have a large impact on anticancer treatment and patients’ quality of life, leading to suboptimal clinical outcomes. As the most important source of dosing instructions, the labeling information should be regularly recalibrated to provide consistent and informative instructions for drug intake in relation to meals, minimizing unintended interactions with meals and improving patient compliance and adherence. Further efforts on harmonizing food recommendations between regulatory agencies are highly warranted to assure optimal outcomes for individual patients. Moreover, meal-drug interaction studies should be conducted as early as possible to inform the dosing schedules of the subsequent phase 2 and phase 3 trials, thereby facilitating regulatory decision-making in regard to the method of drug administration.