Why Prednisone is Given with Abiraterone
Prednisone must be given with abiraterone to prevent potentially serious mineralocorticoid excess side effects caused by abiraterone's mechanism of action, including hypertension, hypokalemia, and peripheral edema. 1
Mechanism Requiring Corticosteroid Co-Administration
Abiraterone works by irreversibly inhibiting CYP17A1, an enzyme that converts progesterone precursors to androgens. This blockade causes a predictable upstream accumulation of mineralocorticoids (aldosterone precursors), leading to increased ACTH levels and subsequent mineralocorticoid excess. 1
The FDA-approved regimen specifically requires abiraterone 1,000 mg once daily to be given with prednisone 5 mg twice daily (or methylprednisolone 4 mg twice daily with the fine-particle formulation). 2
Clinical Consequences Without Corticosteroid Coverage
Without concurrent corticosteroid administration, patients develop mineralocorticoid excess syndrome characterized by:
- Hypertension - occurs in approximately 22% of patients, with severe hypertension in 4% 1
- Hypokalemia - affects 17% of patients 1
- Peripheral edema and fluid retention - seen in 28% of patients 1
- Fatigue - reported in 39% of patients 1
These adverse effects respond to low-dose glucocorticoids, which suppress ACTH and thereby reduce mineralocorticoid production. 1
Evidence from Clinical Trials
The pivotal trials (LATITUDE, STAMPEDE, COU-AA-301, COU-AA-302) that established abiraterone's survival benefit all mandated concurrent prednisone 5 mg twice daily. 1
- In LATITUDE, abiraterone plus prednisone improved median overall survival from 36.5 to 53.3 months (HR 0.66, P<0.0001) in metastatic castration-sensitive prostate cancer 1
- Adverse events were generally mild and manageable with the prednisone regimen, with only 12% discontinuation rate due to side effects 1
Monitoring Requirements
Monthly monitoring is essential during abiraterone therapy, particularly in the initial treatment phase: 1, 3
- Liver function tests (AST/ALT elevations occur in 11-12% of patients) 1
- Serum potassium and phosphate levels 1, 3
- Blood pressure readings 1, 3
- Symptom-directed cardiac assessment, especially in patients with pre-existing cardiovascular disease 1
Alternative Mineralocorticoid Management
While prednisone is the standard and FDA-approved approach, eplerenone (a mineralocorticoid receptor antagonist) has been studied as an alternative in patients who wish to avoid corticosteroids, though this remains off-label. 4 However, spironolactone should be avoided as it can interfere with abiraterone's mechanism of action and reduce efficacy. 5
Common Pitfall to Avoid
Never prescribe abiraterone without concurrent corticosteroid coverage. The drug's mechanism of action makes mineralocorticoid excess inevitable without glucocorticoid suppression of ACTH. Attempting to use abiraterone as monotherapy will result in preventable toxicity and potential treatment discontinuation. 1, 2