Enzalutamide Reduces Oxycodone Exposure in Men with Prostate Cancer.

Area of Science:

• Pharmacology
• Oncology
• Drug Metabolism

Background:

• Castration-resistant prostate cancer (CRPC) frequently leads to bone metastases, necessitating pain management, often with opioids.
• Opioids like oxycodone are commonly used for pain relief in CRPC patients.
• Enzalutamide, an androgen receptor antagonist for CRPC, is a potent inducer of CYP3A4, a key enzyme in oxycodone metabolism.

Purpose of the Study:

• To investigate the potential drug-drug interaction between enzalutamide and oxycodone.
• To quantify the effect of enzalutamide on oxycodone plasma concentrations and its metabolites.

Main Methods:

• A prospective, nonrandomized, open-label, two-arm parallel study.
• Patients received a single 15 mg dose of normal-release oxycodone.
• The enzalutamide arm (ENZ-arm) received 160 mg of enzalutamide daily; plasma concentrations were analyzed using LC-MS/MS.

Main Results:

• Enzalutamide significantly decreased mean oxycodone AUC0-8h by 44.7% and Cmax by 35.5%.
• Exposure to the active metabolite oxymorphone was substantially reduced (AUC0-8h by 74.2%, Cmax by 56.0%).
• Inactive metabolites (noroxycodone, noroxymorphone) showed significantly increased exposure.

Conclusions:

• Co-administration of enzalutamide significantly reduces exposure to oxycodone and its active metabolite oxymorphone.
• Clinicians should consider this interaction when prescribing enzalutamide concurrently with oxycodone for pain management in prostate cancer patients.