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Open Access 10-05-2023 | Prostate Cancer | Original Research Article

Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer

Authors: S. E. H. Detert Oude Weme, L. M. G. Hulskotte, W. L. Vervenne, A. L. T. Imholz, R. G. H. M. Cremers, K. Taxis, A. K. L. Reyners, I. R. F. van Berlo-van de Laar, F. G. A. Jansman, G. E. Benoist

Published in: Clinical Pharmacokinetics | Issue 7/2023

Abstract

Background and objective

Up to 90% of patients with castration-resistant prostate cancer (CRPC) will develop symptomatic bone metastases requiring pain medication, with opioids being the mainstay of therapy in treating moderate and severe pain. Enzalutamide is an androgen receptor antagonist for the treatment of CRPC and a strong inducer of cytochrome P450 (CYP)3A4. Hereby, enzalutamide potentially reduces the exposure of oxycodone, an opioid metabolized by CYP3A4 and CYP2D6. Our objective was to evaluate the potential drug–drug interaction of enzalutamide and oxycodone.

Methods

A prospective, nonrandomized, open-label, two-arm parallel study was performed. All patients received a single dose of 15 mg normal-release oxycodone. Patients in the enzalutamide arm (ENZ-arm) received enzalutamide 160 mg once daily. Plasma concentrations of oxycodone and its metabolites were quantified using a validated liquid chromatography with tandem mass spectrometry (LC–MS/MS) method.

Results

Twenty-six patients (13 ENZ-arm; 13 control arm) were enrolled in the study. Enzalutamide decreased the mean AUC_0–8 h and C_max of oxycodone with, respectively, 44.7% (p < 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC_0–8 h and C_max of the active metabolite oxymorphone were 74.2% (p < 0.001) and 56.0% (p = 0.001) lower in the ENZ-arm compared with the control arm. In contrast, AUC_0–8 h and C_max of the inactive metabolites noroxycodone and noroxymorphone were significantly increased by enzalutamide.

Conclusion

Co-administration of enzalutamide significantly reduced exposure to oxycodone and its active metabolite oxymorphone in men with prostate cancer. This should be taken into account when prescribing enzalutamide combined with oxycodone.

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Title: Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer
Authors: S. E. H. Detert Oude Weme
L. M. G. Hulskotte
W. L. Vervenne
A. L. T. Imholz
R. G. H. M. Cremers
K. Taxis
A. K. L. Reyners
I. R. F. van Berlo-van de Laar
F. G. A. Jansman
G. E. Benoist
Publication date: 10-05-2023
Publisher: Springer International Publishing
Keywords: Prostate Cancer
Prostate Cancer
Oxycodone
Enzalutamide
Published in: Clinical Pharmacokinetics / Issue 7/2023
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-023-01255-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer

Abstract

Background and objective

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and objective

Methods

Results

Conclusion

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