How should abiraterone (Zytiga) be used in patients with impaired renal function?

Abiraterone Use in Renal Impairment

No dose adjustment of abiraterone is required for patients with renal impairment, including those with end-stage renal disease on hemodialysis. 1

Pharmacokinetic Evidence in Renal Impairment

The FDA drug label provides definitive guidance based on pharmacokinetic studies:

• Systemic exposure to abiraterone after a single oral 1,000 mg dose did not increase in subjects with end-stage renal disease on dialysis compared to subjects with normal renal function. 1
• The pharmacokinetic study included 8 patients with ESRD on stable hemodialysis schedules matched with 8 control subjects with normal renal function. 1
• Abiraterone was administered 1 hour after dialysis in the ESRD cohort, with pharmacokinetic sampling up to 96 hours post-dose. 1

Standard Dosing Recommendations

Abiraterone should be administered at the standard dose of 1,000 mg orally once daily on an empty stomach (at least 1 hour before or 2 hours after food) with prednisone 5 mg twice daily, regardless of renal function. 2, 1

Alternative Dosing Options

For patients who cannot afford or comply with standard dosing:

• 250 mg daily with a low-fat breakfast can be considered as a cost-saving alternative, though this is off-label and requires close monitoring for excess toxicity. 2
• The fine-particle formulation at 500 mg daily with methylprednisolone 4 mg twice daily is FDA-approved and bioequivalent to standard dosing. 2

Essential Monitoring in Renal Impairment

Monthly monitoring is critical during abiraterone therapy, particularly in patients with pre-existing renal dysfunction: 2

• Liver function tests (ALT, AST, bilirubin)
• Serum electrolytes (potassium and phosphate levels)
• Blood pressure readings
• Cardiac assessment, especially in patients with pre-existing cardiovascular disease

Mineralocorticoid Excess Monitoring

Concurrent steroid administration is mandatory to prevent mineralocorticoid excess, which manifests as: 2

• Hypertension
• Hypokalemia
• Peripheral edema

Clinical Evidence in Renal Disease

Case reports demonstrate that abiraterone can improve renal function in patients with metastatic castration-resistant prostate cancer and chronic kidney disease. 3 Two patients who developed worsening renal function with conventional chemotherapy showed improvements in both renal function and disease response after switching to abiraterone. 3

Important Safety Considerations

Rhabdomyolysis Risk

Strict monitoring should be employed in patients with additional risk factors for rhabdomyolysis, as abiraterone has been associated with rhabdomyolysis resulting in acute kidney injury. 4 This is particularly relevant in patients with pre-existing chronic kidney disease.

Drug Interactions

Abiraterone is a substrate of CYP3A4 and inhibits multiple cytochrome P450 enzymes (CYP1A2, CYP2D6, CYP2C8). 1 In patients with renal impairment who may be on multiple medications:

• Avoid strong CYP3A4 inducers (e.g., rifampin), which decrease abiraterone exposure by 55%. 1
• Monitor closely when co-administering CYP2D6 substrates (e.g., dextromethorphan), as abiraterone increases their exposure 2.8-2.9 fold. 1

Practical Clinical Algorithm

1. Assess baseline renal function - No dose adjustment needed regardless of severity
2. Initiate standard dosing: 1,000 mg daily fasting + prednisone 5 mg twice daily 2, 1
3. Establish monthly monitoring for liver function, electrolytes, and blood pressure 2
4. Watch for mineralocorticoid excess (hypertension, hypokalemia, edema) 2
5. Monitor for rhabdomyolysis in high-risk patients (muscle pain, weakness, dark urine) 4
6. Consider alternative dosing only if financial barriers or compliance issues exist 2