Why Prednisolone is Co-Administered with Abiraterone
Prednisolone (or prednisone) must be co-administered with abiraterone to prevent life-threatening mineralocorticoid excess syndrome caused by abiraterone's mechanism of action—specifically, the upstream accumulation of mineralocorticoids that occurs when CYP17A1 is inhibited. 1, 2
Mechanism of Mineralocorticoid Excess
Abiraterone irreversibly inhibits CYP17A1, the enzyme essential for androgen biosynthesis, but this blockade causes a predictable upstream accumulation of mineralocorticoid precursors in the steroidogenic pathway. 2, 3
Without concurrent glucocorticoid administration, the body compensates by increasing ACTH levels, which further drives mineralocorticoid production and creates a syndrome of mineralocorticoid excess. 2, 4
The low-dose glucocorticoid (prednisone 5 mg twice daily or prednisolone equivalent) suppresses ACTH release, thereby reducing the compensatory mineralocorticoid surge and acting as physiologic glucocorticoid replacement therapy. 2, 4
Clinical Consequences Without Corticosteroid Co-Administration
Hypertension develops in approximately 22% of patients overall, with severe hypertension occurring in 4% of cases when abiraterone is used without adequate corticosteroid coverage. 1
Hypokalemia affects 17% of patients and can lead to cardiac arrhythmias and muscle weakness if left unmanaged. 1
Peripheral edema and fluid retention occur in 28% of patients due to mineralocorticoid-mediated sodium and water retention. 1
Cardiac complications, including atrial fibrillation, occur more frequently without proper mineralocorticoid control, though rates remain relatively low (4%) even with standard dosing. 1
FDA-Approved Dosing Regimens
The standard FDA-approved regimen is abiraterone acetate 1,000 mg orally once daily combined with prednisone 5 mg orally twice daily, taken on an empty stomach. 5
An alternative fine-particle formulation uses abiraterone 500 mg daily with methylprednisolone 4 mg twice daily, which is bioequivalent to the standard formulation. 1
The corticosteroid component is mandatory, not optional—the FDA indication explicitly states abiraterone must be used "in combination with prednisone." 5
Evidence from Pivotal Trials
All major trials establishing abiraterone's survival benefit (LATITUDE, STAMPEDE, COU-AA-301, COU-AA-302) included mandatory prednisone co-administration, making the combination the evidence-based standard of care. 1, 2
In LATITUDE, the combination of 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, with only a 12% discontinuation rate due to side effects. 1, 2, 6
The COU-AA-302 trial in chemotherapy-naïve metastatic CRPC demonstrated improved overall survival (34.7 vs 30.3 months; HR 0.81, P=0.003) with the abiraterone-prednisone combination. 1
Mandatory Monitoring Requirements
Monthly monitoring is essential, particularly during initial treatment phases, and must include: 1, 2
- Blood pressure measurements to detect hypertension early
- Serum potassium and phosphate levels to identify electrolyte disturbances
- Liver function tests (AST/ALT) as hepatotoxicity can be severe and fatal
- Symptom-directed cardiac assessment, especially in patients with pre-existing cardiovascular disease
Critical Pitfalls to Avoid
Never use spironolactone as an alternative mineralocorticoid antagonist, as it interferes with abiraterone's mechanism of action by blocking the androgen receptor and reducing treatment efficacy. 2
Some patients may attempt to avoid steroids with abiraterone, but this requires extremely careful monitoring, and a mineralocorticoid receptor antagonist (such as eplerenone, not spironolactone) or steroid must be added immediately if mineralocorticoid excess symptoms develop. 1, 2
Do not switch between prednisone and methylprednisolone formulations after disease progression—abiraterone with one steroid should not be given following progression on abiraterone with the other steroid. 1
Alternative Mineralocorticoid Management
Eplerenone (a selective mineralocorticoid receptor antagonist) has been studied as an off-label alternative for patients who wish to avoid corticosteroids, though this approach requires vigilant monitoring and is not FDA-approved. 2
The glucocorticoid dose used with abiraterone (prednisone 5 mg twice daily) is physiologic replacement rather than pharmacologic immunosuppression, minimizing concerns about long-term glucocorticoid toxicity such as bone loss, immunosuppression, or hyperglycemia that occur at higher doses. 4