Side Effects of Abiraterone (Zytiga)
Abiraterone acetate commonly causes hypertension, hypokalemia, peripheral edema, atrial fibrillation, congestive heart failure, liver injury, and fatigue, requiring regular monitoring during treatment. 1
Common Side Effects
Abiraterone has several significant side effects that require careful monitoring and management:
Cardiovascular and Fluid-Related Effects
- Hypertension (22%, severe in 4%) 1
- Peripheral edema (28%) 1
- Atrial fibrillation (4%) 1
- Congestive heart failure 1
Electrolyte Abnormalities
Gastrointestinal Effects
Hepatic Effects
- Liver injury with increased AST/ALT (11-12% leading to discontinuation) 1
Other Common Side Effects
- Fatigue (39%) 1
- Back or joint discomfort (28-32%) 1
- Hot flushes (22%) 1
- Urinary tract infection 1
- Urinary frequency and nocturia 1
- Cough 1
- Upper respiratory tract infection 1
Mineralocorticoid Excess Syndrome
A key mechanism behind many side effects is mineralocorticoid excess due to abiraterone's inhibition of CYP17A1:
- Abiraterone blocks cortisol production, leading to increased ACTH release 2
- This causes increased mineralocorticoid production 2
- Results in sodium retention, potassium excretion, and hypertension 2
This is why abiraterone must be administered with prednisone (5 mg twice daily) or methylprednisolone (4 mg twice daily) to suppress ACTH and prevent these effects 1.
Monitoring Requirements
Regular monitoring is essential during abiraterone treatment:
- Blood pressure - monthly checks 1
- Potassium levels - monthly checks 1
- Liver function tests - monthly, at least initially 1
- Phosphate levels - monthly 1
- Signs of fluid retention - monthly 1
- Cardiac symptoms - symptom-directed assessment 1
Administration Considerations
- Must be taken on an empty stomach (at least 1 hour before or 2 hours after meals) 3
- Tablets should be swallowed whole with water 3
- Standard dose is 1,000 mg daily with prednisone 5 mg twice daily 1
- Alternative lower-cost option: 250 mg daily with a low-fat breakfast 1
- Fine-particle formulation (500 mg) is bioequivalent to 1,000 mg of original formulation 1
Important Precautions
Never discontinue prednisone/prednisolone abruptly - can lead to adrenal insufficiency 4
Individualized steroid dosing may be needed - standard prednisone dose (5 mg twice daily) may be inadequate for some patients 4
Monitor for adrenal insufficiency - especially during times of stress 4
Diabetic patients require close glucose monitoring - severe hypoglycemia can occur 3
Maintain castrate testosterone levels - continue androgen deprivation therapy 1
Special Considerations
- Patients with pre-existing cardiovascular disease require particularly careful monitoring 1
- Amiloride may be considered for managing residual mineralocorticoid activity in some cases 2
- Food significantly impacts absorption, which can lead to unpredictable effects 1, 3
By understanding these side effects and implementing appropriate monitoring, the risks associated with abiraterone therapy can be effectively managed while providing its survival benefits for patients with metastatic castration-resistant prostate cancer.