Can Korlym (mifepristone) interfere with Jatenzo (testosterone undecanoate)?

Drug Interaction Between Korlym (Mifepristone) and Jatenzo (Testosterone Undecanoate)

Yes, Korlym (mifepristone) can significantly interfere with Jatenzo (testosterone undecanoate) through multiple mechanisms that may compromise the effectiveness of testosterone replacement therapy and complicate clinical management.

Primary Mechanism of Interference

Mifepristone blocks the androgen receptor directly, which means it will antagonize the therapeutic effects of testosterone replacement therapy at the receptor level, regardless of serum testosterone concentrations 1. This creates a fundamental pharmacodynamic conflict where:

• Mifepristone competitively inhibits testosterone binding to the androgen receptor 2
• The glucocorticoid receptor blockade by mifepristone paradoxically increases endogenous testosterone production by 91% and DHT by 80% through ACTH-mediated adrenal androgen stimulation 2
• Despite elevated testosterone levels, the clinical benefits of testosterone therapy will be blunted due to receptor-level antagonism 2

Critical Monitoring Challenges

The combination creates an unmonitorable clinical scenario because:

• Serum testosterone levels will be artificially elevated and cannot be used to guide Jatenzo dosing 1, 2
• Mifepristone eliminates the reliability of biochemical markers for assessing either medication's efficacy 3, 1
• Clinical features alone must guide management, but symptoms of hypogonadism may persist despite high testosterone levels due to receptor blockade 1, 2

Endocrine Consequences

The combination produces complex hormonal perturbations:

• ACTH elevation from glucocorticoid receptor blockade stimulates adrenal androgen production 2
• Testosterone and DHT levels increase substantially (91% and 80% respectively) within one month 2
• These elevated androgens are converted from adrenal precursors but remain functionally blocked at the receptor level 2
• Thyroid function requires close monitoring as mifepristone affects thyroid hormone metabolism independently of testosterone 3

Clinical Recommendation

Avoid this combination whenever possible. If a patient requires both medications:

• Prioritize treatment of Cushing's disease first, as this is typically the more immediately life-threatening condition 3
• Consider alternative Cushing's disease treatments that do not cause androgen receptor blockade, such as osilodrostat or metyrapone, which do not cause hypogonadism in men 3, 1
• If mifepristone is essential (e.g., for refractory hyperglycemia in Cushing's disease), discontinue Jatenzo as it will provide minimal clinical benefit while complicating the hormonal picture 1, 2
• Only prescribe mifepristone through clinicians with extensive Cushing's disease experience who can manage the complex drug interactions 3, 4

Common Pitfalls to Avoid

• Do not attempt to titrate Jatenzo based on serum testosterone levels during concurrent mifepristone therapy, as levels will be misleadingly elevated 2
• Do not assume higher testosterone doses will overcome receptor blockade—this will only worsen the hormonal dysregulation 2
• Do not overlook the need for comprehensive medication review before initiating mifepristone, as it has significant potential for multiple drug-drug interactions 3, 4
• Do not rely on typical hypogonadism symptoms to assess Jatenzo efficacy, as mifepristone's effects on multiple hormone systems will confound clinical assessment 1, 2