Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer.

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 AUC0-8 h and Cmax of oxycodone with, respectively, 44.7% (p < 0.001) and 35.5% (p = 0.004) compared with the control arm. The AUC0-8 h and Cmax 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, AUC0-8 h and Cmax 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.

[Hormone therapy in prostate cancer; a pharmacotherapeutic challenge]. / Hormonale therapie bij prostaatkanker; een farmacotherapeutische uitdaging.

Prostate cancer is the most common form of cancer in men in the Western world. One-third of the patients with localised prostate cancer will develop recurrent disease, localised disease spread or distant metastases. The presence of distant metastases is an indication for primary palliative hormone therapy. Intervention in the testosterone metabolism using hormone therapy is frequently accompanied by side effects and has a negative influence on the quality of life. Almost all prostate cancer patients show disease progression while on primary hormone therapy, despite having testosterone concentrations at castration level; they are then said to have castration-resistant prostate cancer (CRPC). The CYP17 inhibitor abiraterone and the non-steroidal anti-androgen enzalutamide are second-generation hormone therapies for metastatic CRPC both before and after treatment with standard docetaxel-based chemotherapy. Abiraterone and enzalutamide can lead to many interactions with other drugs or food. This can lead to higher or lower levels of both the hormone therapy and comedications.