A Multicenter Retrospective Observational Study Analyzing the Effect of Polypharmacy on Oxycodone Tolerability

Abstract

Polypharmacy is becoming increasingly troublesome in the treatment of cancer. The aim of this study was to explore the effects of concomitant polypharmacy comprising drugs that inhibit CYP3A4 and/or CYP2D6 on the oxycodone tolerability in patients with cancer. We conducted a multicenter retrospective study encompassing 20 hospitals. The data used for the study were obtained during the first 2 wk of oxycodone administration. The incidence of oxycodone discontinuation or dose reductions due to side effects and oxycodone-induced nausea and vomiting (OINV) were compared between patients not treated with either inhibitor and those treated with concomitant CYP3A4 or CYP2D6 inhibitors. The incidence of oxycodone discontinuation or dose reductions in patients treated with ≥3 concomitant CYP2D6 inhibitors (18.2%) tended to be higher than that in patients without this treatment (8.2%; p = 0.09). Moreover, the incidence of OINV in patients treated with 2 concomitant CYP3A4 inhibitors (29.8%) was significantly higher than that in patients without this treatment (15.5%; p = 0.049). Multivariate analysis showed that more than two concomitant CYP3A4 inhibitors and no concomitant use of naldemedine were independent risk factors for OINV. Concomitant polypharmacy involving CYP3A4 inhibitors increases the risk of OINV. Therefore, medications concomitantly used with oxycodone should be optimized.

Keywords:

• Polypharmacy
• oxycodone
• cytochromes P450 3A4
• cytochromes P450 2D6
• drug–drug interaction
• oxycodone-induced nausea and vomiting

Acknowledgments

We express our sincere thanks to Yasunori Miyamoto, Keisuke Kongo, Kayo Tsujii, Takashi Miyabe, Tetsuya Arai, Masami Yamada, Hiroko Tanaka, Yuki Ozawa, Shinichi Tomii, Hiroki Sugiyama, Katsuya Omori, Rintaro Ohno, Hiroki Mase, Tatsuya Hirano, Ayuko Kano, Yoshika Takeuchi, Mika Ishikawa, and Shun Orikasa for the collection of data. We would also like to thank Editage (www.editage.jp) for English language editing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Data available within the article.

Additional information

Funding

The author(s) received financial support for the research, authorship, and/or publication of this article from the Japanese Society for Pharmaceutical Palliative Care and Sciences.