Is eplerenone better than spironolactone for managing mineralocorticoid excess in patients on abiraterone (generic name for Zytiga) for metastatic castration-resistant prostate cancer?

Eplerenone is Better Than Spironolactone for Managing Mineralocorticoid Excess in Patients on Abiraterone

Eplerenone is superior to spironolactone for managing mineralocorticoid excess in patients on abiraterone for metastatic castration-resistant prostate cancer due to its more favorable side effect profile and lack of androgen receptor activity.

Background on Abiraterone and Mineralocorticoid Excess

• Abiraterone acetate is FDA-approved for metastatic castration-resistant prostate cancer (mCRPC) and has demonstrated significant survival benefits in clinical trials such as LATITUDE and STAMPEDE 1
• Abiraterone inhibits CYP17, which suppresses androgen synthesis but leads to mineralocorticoid excess, causing side effects including hypertension, hypokalemia, and edema 1
• These mineralocorticoid excess symptoms occur in the majority of patients taking abiraterone without preventive measures 2

Comparison of Eplerenone vs. Spironolactone

Efficacy

• Both eplerenone and spironolactone are mineralocorticoid receptor antagonists that can effectively manage the mineralocorticoid excess syndrome caused by abiraterone 3, 4
• A retrospective study demonstrated that eplerenone with abiraterone (without prednisone) provided similar control of mineralocorticoid excess symptoms compared to the standard abiraterone plus prednisone regimen 5

Side Effect Profiles

• Eplerenone has significantly fewer hormonal side effects compared to spironolactone due to its selective binding to mineralocorticoid receptors 3, 4
• Spironolactone causes gynecomastia and sexual dysfunction in men due to its non-selective binding to progesterone and androgen receptors 3, 4

Critical Consideration for Prostate Cancer Patients

• Spironolactone has been shown to act as an androgen receptor agonist in androgen-depleted environments, potentially stimulating prostate cancer proliferation 6
• Case reports document disease progression in mCRPC patients when spironolactone was added to abiraterone therapy, with improvement after spironolactone discontinuation 6

Management Algorithm for Mineralocorticoid Excess in Abiraterone Patients

1. First-line approach: Abiraterone with prednisone 5mg daily is the standard FDA-approved regimen to prevent mineralocorticoid excess 1

2. For patients who cannot or prefer not to take prednisone:

   • Eplerenone is the preferred mineralocorticoid antagonist 2, 5
   • Initial dosage should be 25mg once daily, titrated to 50mg once daily within 4 weeks as needed 4
   • Close monitoring of blood pressure, fluid retention, and potassium levels is essential 4, 2

3. Monitoring requirements:

   • Baseline and periodic assessment of serum potassium and renal function 4, 7
   • Regular blood pressure monitoring 2, 7
   • Evaluation for signs of fluid retention 2

Common Pitfalls and Caveats

• Avoid spironolactone completely in patients with prostate cancer on abiraterone due to its potential to stimulate cancer progression through androgen receptor activation 6
• Approximately 12% of patients on abiraterone without prednisone will still require glucocorticoid therapy for mineralocorticoid toxicity despite eplerenone use 7
• Patients with lower baseline levels of certain adrenal androgens (androstenedione, androsterone, dehydroepiandrosterone, and 17-hydroxyprogesterone) may be more likely to develop mineralocorticoid toxicity and require closer monitoring 7
• Both eplerenone and spironolactone can cause hyperkalemia, requiring regular monitoring of potassium levels, especially in patients with renal impairment 3, 4