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

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.