What are the side effects of abiraterone?

Side Effects of Abiraterone

Abiraterone causes mineralocorticoid excess side effects—including hypertension, hypokalemia, and peripheral edema—which occur because the drug blocks CYP17A, leading to upstream accumulation of mineralocorticoids; these effects are managed with concurrent steroid administration and require monthly monitoring of blood pressure, potassium, and liver function. 1

Mechanism of Side Effects

Abiraterone inhibits CYP17A, which blocks androgen synthesis but causes accumulation of mineralocorticoid precursors upstream of the enzyme, leading to ACTH-driven mineralocorticoid excess. 1 This mechanism directly explains the characteristic side effect profile and why concurrent glucocorticoid therapy is mandatory. 1

Common Side Effects (>5% incidence)

Mineralocorticoid-Related Effects

• Hypertension: Occurs in 22% of patients overall, with severe hypertension (grade 3-4) in 4-15.5% 1, 2
• Hypokalemia: Affects 17% of patients, with grade 3-4 events in 7-12% 1, 3
• Peripheral edema: Occurs in 28% of patients 1
• Fluid retention: Can be life-threatening if not managed appropriately 4

General Side Effects

• Fatigue: Most common adverse reaction at 39% 1
• Musculoskeletal symptoms: Back or joint discomfort in 28-32% 1
• Gastrointestinal effects: Diarrhea, nausea, or constipation in 22% 1
• Hot flushes: Occur in 22% of patients 1
• Urinary tract infections: Common occurrence 1
• Cough and upper respiratory infections: Frequently reported 1

Metabolic Abnormalities

• Hypophosphatemia: Affects 24% of patients 1
• Elevated liver enzymes: AST/ALT increases lead to drug discontinuation in 11-12% 1
• Anemia: Low red blood cells commonly observed 4
• Dyslipidemia: High cholesterol and triglycerides 4

Serious Adverse Events

Cardiac Complications

• Atrial fibrillation: Occurs in 4% of patients 1
• Cardiac disorders: Lead to discontinuation in 19% of patients, with serious events in 6% 1
• Irregular heartbeats: Can be life-threatening and require immediate attention 4

Hepatotoxicity

• Liver function abnormalities: More common in the abiraterone group, with grade 3-4 events requiring monitoring 1
• Severe liver problems: Can progress to liver failure and death 4
• Warning signs: Yellowing of skin/eyes, dark urine, severe nausea/vomiting require immediate medical attention 4

Endocrine Complications

• Adrenal insufficiency: May occur if prednisone is stopped, during infection, or under stress 4
• Severe hypoglycemia: Occurs in diabetic patients taking antidiabetic medications, requiring blood sugar monitoring 4

Other Serious Events

• Increased fracture risk: Occurs when abiraterone is combined with radium-223 radiation therapy 4
• Increased mortality risk: Also associated with radium-223 combination 4
• Fertility problems: May affect ability to father children 4

Critical Monitoring Requirements

Monthly Monitoring (Minimum)

• Blood pressure readings: Essential to detect hypertension early 1
• Serum potassium levels: Monitor for hypokalemia 1
• Serum phosphate levels: Check for hypophosphatemia 1
• Liver function tests: AST, ALT monitoring before and during treatment 1

Cardiac Surveillance

• Symptom-directed assessment: Particularly important in patients with pre-existing cardiovascular disease 1
• Watch for: Dizziness, fast/irregular heartbeats, feeling faint, confusion, muscle weakness, leg pain 4

Diabetic Patients

• Regular blood sugar monitoring: During and after treatment with abiraterone 4
• Antidiabetic medication adjustment: May be necessary 4
• Hypoglycemia symptoms: Headache, drowsiness, weakness, confusion, irritability, hunger, fast heartbeat, sweating 4

Management Strategies

Mandatory Concurrent Steroid Therapy

• Standard regimen: Prednisone 5 mg orally twice daily with original formulation 1
• Alternative regimen: Methylprednisolone 4 mg orally twice daily with fine-particle formulation 1
• Purpose: Prevents ACTH-driven mineralocorticoid excess 1
• Critical warning: Never discontinue steroids without medical supervision due to adrenal insufficiency risk 4

Mineralocorticoid Receptor Antagonists

• Eplerenone consideration: Can be added but does not fully control mineralocorticoid excess alone 5
• Spironolactone avoidance: Should NOT be used as it interferes with abiraterone's mechanism of action 6, 7

Dose Modifications for Toxicity Management

• Switching to dexamethasone: Consider dexamethasone 0.5-1 mg/day for patients progressing on abiraterone with prednisone 1, 6
• Lower-dose alternative: Abiraterone 250 mg/day with low-fat breakfast shows similar efficacy to standard 1000 mg fasting dose, potentially reducing financial toxicity 1

Common Pitfalls to Avoid

Administration Errors

• Food interaction: Taking abiraterone with food increases absorption unpredictably and may worsen side effects 1, 4
• Standard dosing: Must be taken on empty stomach (1 hour before or 2 hours after meals) 4
• Tablet integrity: Never crush or chew tablets 4

Monitoring Failures

• Inadequate frequency: Monthly monitoring is minimum; some patients may require more frequent assessment initially 1
• Missed drug interactions: Particularly important in diabetic patients on antidiabetic medications 4
• Cardiovascular risk underestimation: Pre-existing cardiac disease requires heightened surveillance 1

Treatment Combinations

• Radium-223 contraindication: Combination increases fracture risk and mortality 4
• Spironolactone error: Using spironolactone instead of other MR antagonists reduces abiraterone efficacy 6, 7

Comparative Safety Profile

The fine-particle formulation (500 mg with methylprednisolone) shows similar adverse event rates to the original formulation, though musculoskeletal disorders occur less frequently (12.5% vs 37.9%). 1 Grade 3-4 mineralocorticoid-related adverse events and liver abnormalities are more common with abiraterone than placebo, but the agent is generally well-tolerated when properly monitored. 1