What is the appropriate management and monitoring for a patient taking Zytiga (abiraterone) and prednisone for prostate cancer?

Abiraterone (Zytiga) Management for Prostate Cancer

Abiraterone (Zytiga) should be administered as 1000 mg (four 250 mg tablets) once daily on an empty stomach with 5 mg prednisone once daily with food, with regular monitoring of blood pressure, liver function, potassium levels, and signs of fluid retention to prevent serious complications.

Standard Dosing and Administration

• Dosage: Abiraterone 1000 mg (four 250 mg tablets) once daily with prednisone 5 mg once daily 1
• Administration timing:
  • Abiraterone must be taken on an empty stomach (1 hour before or 2 hours after meals) as food significantly increases absorption leading to unpredictable effects 1, 2
  • Prednisone should be taken with food (typically breakfast) 1
• Duration: Continue until disease progression is documented 3
• Concurrent therapy: Patients should continue androgen deprivation therapy (ADT) to maintain castrate testosterone levels 1

Mechanism of Action

Abiraterone works by blocking testosterone synthesis through inhibition of the CYP17 enzyme, which:

• Reduces androgen-driven prostate cancer growth
• Affects the adrenal pathway, necessitating prednisone supplementation
• Suppresses testosterone production throughout the body 1

Required Monitoring

Regular monitoring is essential during abiraterone treatment:

1. Blood pressure: Monthly monitoring (22% develop hypertension) 1
2. Liver function tests (AST/ALT):
   • Monthly for the first 3 months, then as clinically indicated
   • 11-12% develop liver injury which can be severe or fatal 1, 2
3. Potassium levels: Monthly (17-28% develop hypokalemia) 1
4. Phosphate levels: Monthly (24% develop hypophosphatemia) 1
5. Signs of fluid retention: Monthly (28% develop peripheral edema) 1
6. PSA levels: Regular monitoring to assess treatment response 1
7. Complete blood count: Regular monitoring 1

Side Effect Management

Common side effects requiring management:

• Hypertension (22% of patients): Control before and during treatment 1, 2
• Fluid retention/edema (28% of patients): Monitor closely, especially in patients with cardiac conditions 1, 2
• Hypokalemia (17-28% of patients): Correct before and during treatment 1, 2
• Liver toxicity (11-12% of patients): Hold treatment if ALT/AST >5x ULN or bilirubin >3x ULN 2
• Fatigue (39% of patients): Monitor and manage symptomatically 1
• Joint/back discomfort (28-32% of patients): Provide appropriate pain management 1
• Hyperglycemia: Monitor blood glucose in diabetic patients 1, 2

Prednisone Management

• Purpose: Prednisone prevents mineralocorticoid excess caused by abiraterone's inhibition of adrenal steroid synthesis 1, 2
• Discontinuation: Prednisone should not be stopped abruptly when abiraterone is discontinued but rather tapered gradually to prevent adrenal insufficiency 1
• Monitoring: Watch for signs of adrenocortical insufficiency, particularly during stress or if prednisone doses are reduced 2

Dose Modifications for Toxicity

For hepatotoxicity:

1. Hold treatment if ALT/AST >5x ULN or bilirubin >3x ULN
2. Restart at reduced dose (750 mg daily) after liver function returns to baseline or ALT/AST ≤2.5x ULN and bilirubin ≤1.5x ULN
3. Further reduce to 500 mg if hepatotoxicity recurs
4. Permanently discontinue if hepatotoxicity recurs at 500 mg or if ALT >3x ULN and bilirubin >2x ULN concurrently 2

Special Considerations

• Handling precautions: Wash hands after handling abiraterone tablets (hazard precaution) 1
• Drug interactions: Avoid strong CYP3A4 inducers; if necessary, increase abiraterone dosing frequency 2
• Cardiac monitoring: Patients with pre-existing cardiovascular disease require particularly careful monitoring 1
• Hypoglycemia risk: Monitor blood glucose in patients with diabetes taking thiazolidinediones or repaglinide 2

Important Caveats

• Abiraterone is not chemotherapy but requires hazard precautions when handling 1
• Prednisone is an essential component of therapy and should not be discontinued without proper tapering 1, 2
• The safety of abiraterone in patients with NYHA Class III-IV heart failure or LVEF <50% has not been established 2
• QT prolongation and Torsades de Pointes have been observed in patients who develop hypokalemia while taking abiraterone 2