Why Prednisolone is Co-Administered with Abiraterone
Prednisolone (or prednisone) must be co-administered with abiraterone to prevent mineralocorticoid excess syndrome, which occurs because abiraterone's inhibition of CYP17A1 causes upstream accumulation of mineralocorticoids, leading to hypertension, hypokalemia, and peripheral edema. 1
Mechanism of Action
Abiraterone works by irreversibly inhibiting the enzyme CYP17A1, which is essential for androgen biosynthesis. 1 This inhibition has a predictable consequence: it causes upstream accumulation of mineralocorticoid precursors and triggers increased ACTH levels, resulting in mineralocorticoid excess syndrome. 1
Without concurrent corticosteroid administration, patients develop:
- Hypertension in approximately 22% of patients (severe hypertension in 4%) 2
- Hypokalemia affecting 17% of patients 2
- Peripheral edema and fluid retention in 28% of patients 2
Clinical Evidence and Dosing
The standard regimen is abiraterone 1,000 mg orally once daily plus prednisone 5 mg orally twice daily (or methylprednisolone 4 mg twice daily with the fine-particle formulation). 2, 3
This dosing was established in pivotal trials including:
- COU-AA-301 (post-chemotherapy mCRPC): median survival 15.8 vs 11.2 months (HR 0.74, P<0.0001) 2
- COU-AA-302 (chemotherapy-naïve mCRPC): median survival 34.7 vs 30.3 months (HR 0.81, P=0.003) with radiographic PFS improved from 8.3 to 16.5 months (HR 0.53, P<0.001) 2
- LATITUDE (metastatic castration-sensitive): median survival 53.3 vs 36.5 months (HR 0.66, P<0.0001) 1
All these trials used abiraterone with concurrent prednisone, establishing this combination as the evidence-based standard. 2
Role of Glucocorticoid Replacement
The prednisone 5 mg twice daily dose functions as glucocorticoid replacement therapy rather than immunosuppressive therapy. 4 It compensates for abiraterone-induced reductions in serum cortisol and blocks the compensatory increase in ACTH that would otherwise drive mineralocorticoid production. 4
This low-dose glucocorticoid regimen:
- Suppresses ACTH secretion 1
- Reduces mineralocorticoid production 1
- Manages fatigue (reported in 39% of patients) 1
- Prevents adrenocortical insufficiency during treatment 3
Monitoring Requirements
Monthly monitoring is essential during abiraterone therapy, particularly initially, and must include: 2
- Blood pressure readings
- Serum potassium levels
- Serum phosphate levels (hypophosphatemia occurs in 24% of patients) 2
- Liver function tests
- Symptom-directed cardiac assessment, especially in patients with pre-existing cardiovascular disease 2
Alternative Approaches and Important Caveats
Some patients may be able to avoid steroids with abiraterone, but this requires careful monitoring. 2 If mineralocorticoid excess symptoms develop, either a mineralocorticoid receptor antagonist or a steroid should be added immediately. 2
Eplerenone (a mineralocorticoid receptor antagonist) has been studied as an off-label alternative for patients wishing to avoid corticosteroids. 1
Critical warning: Spironolactone should be avoided as it can interfere with abiraterone's mechanism of action and reduce efficacy. 5
The fine-particle formulation of abiraterone (500 mg daily) with methylprednisolone (4 mg twice daily) is bioequivalent to the standard formulation and represents an acceptable alternative. 2 However, switching between formulations after disease progression is not recommended. 2