Should Abiraterone acetate (abiraterone) be taken with food or on an empty stomach for optimal absorption in a patient with prostate cancer?

Abiraterone Acetate Administration: Empty Stomach vs. Food

Abiraterone acetate must be taken on an empty stomach at the standard dose of 1,000 mg once daily, despite the fact that food significantly increases absorption, because the unpredictable variability in bioavailability with food poses safety and efficacy concerns. 1

FDA-Approved Administration Requirements

The FDA label explicitly mandates specific fasting requirements for abiraterone acetate administration 1:

• Take on an empty stomach: No food for 2 hours before and 1 hour after administration 1
• Standard dose: 1,000 mg orally once daily with prednisone 1
• Swallow whole with water: Do not crush or chew tablets 1

Why Food Increases Absorption But Is Not Recommended

The Food Effect Paradox

Food dramatically increases abiraterone absorption, but this creates problems rather than benefits 2:

• Low-fat meals: Increase exposure approximately 5-fold in healthy subjects and 2-fold in patients 2
• High-fat meals: Increase exposure approximately 10-fold in healthy subjects and 2-fold in patients 2
• Unpredictable variability: The drug's poor water solubility leads to highly variable bioavailability when taken with food, making dosing unreliable 3

Clinical Guideline Position

ASCO guidelines explicitly state that the standard regimen is abiraterone 1,000 mg on an empty stomach, and do not support alternative dosing with food in routine practice. 3

The guideline panel acknowledges that 250 mg with a low-fat breakfast showed non-inferiority in a small phase II trial for castration-resistant prostate cancer, but they do not recommend this approach because 3:

• PSA response at 12 weeks is not a validated surrogate for metastasis-free survival or overall survival
• The ability of patients to consistently comply with a "low-fat breakfast" outside clinical trials is unclear
• Similar trials have not been conducted in the non-castrate setting

Alternative Formulations

Micronized Fine-Particle Formulation

A micronized formulation (Sun Pharma Global) was designed to overcome food-related effects 3:

• Dose: 500 mg daily with methylprednisolone 4 mg twice daily 3
• FDA approval: Only for metastatic castration-resistant prostate cancer, NOT for non-castrate disease 3
• Not interchangeable: The two formulations have different indications and dosing 3
• ASCO position: Does not support use of micronized formulation in non-castrate setting 3

NCCN Alternative Dosing Option

NCCN guidelines mention that 250 mg/day with a low-fat breakfast can be given as an alternative to 1,000 mg fasted, but with important caveats 3:

• Cost consideration: May reduce financial toxicity and improve compliance 3
• Critical warning: Food impacts absorption unpredictably; monitor for excess toxicity and revert to standard dosing (1,000 mg empty stomach) if toxicity occurs 3
• Not first-line: This is presented as an alternative, not the preferred approach 3

Practical Clinical Algorithm

For standard practice, follow this approach:

1. Prescribe standard FDA-approved regimen: Abiraterone 1,000 mg once daily on empty stomach (no food 2 hours before, 1 hour after) with prednisone 5 mg twice daily 1

2. Patient education is critical: Emphasize strict fasting requirements to avoid unpredictable drug exposure 1

3. If patient cannot comply with fasting: Consider switching to enzalutamide 160 mg daily, which does not require fasting or concurrent steroids 3, 4

4. Only consider food-based dosing if:

   • Standard dosing is financially prohibitive
   • Patient has demonstrated inability to take medication fasted
   • Close monitoring for toxicity is feasible
   • Patient understands this is off-label use 3

Monitoring Requirements

Regardless of administration method, monthly monitoring is essential 5:

• Liver function tests: ALT, AST, bilirubin 5
• Electrolytes: Serum potassium and phosphate 5
• Blood pressure: Monitor for hypertension 5
• Cardiac assessment: Especially in patients with pre-existing cardiovascular disease 5

Common Pitfalls to Avoid

Do not assume "with food" is better simply because absorption increases - the unpredictability of the food effect creates more problems than it solves 3, 2. The clinical trials that established abiraterone's survival benefit used the fasted dosing regimen 3.

Do not switch between formulations (original vs. micronized) or between dosing strategies (fasted vs. with food) based on disease progression alone - these are not interchangeable 3.

Do not use spironolactone to manage mineralocorticoid excess, as it interferes with abiraterone's mechanism of action 4, 5.