What are the side effects of Apalutamide (Erleada)?

Side Effects of Apalutamide (Erleada)

Apalutamide commonly causes rash (23.8% vs 5.5% with placebo), fatigue (30.4% vs 21.1%), fractures (11.7% vs 6.5%), falls (15.6% vs 9.0%), and hypothyroidism (8.1% vs 2.0%) as its most significant side effects requiring monitoring and management. 1

Common Side Effects

According to the FDA label and clinical guidelines, the most common side effects of apalutamide include:

• Skin reactions:

  • Rash (24% vs 5.5% with placebo) 2, 3
  • Most commonly macular or maculo-papular 3
  • Usually appears early in treatment course 1

• Constitutional symptoms:

  • Fatigue/asthenia (30.4% vs 21.1%) 1, 3
  • Weight loss (16.1% vs 6.3%) 1

• Musculoskeletal issues:

  • Arthralgia (15.9% vs 7.5%) 1
  • Falls (15.6% vs 9.0%) 1, 3
  • Fractures (11.7% vs 6.5%) 1, 3

• Cardiovascular effects:

  • Hypertension (24.8% vs 19.8%) 1
  • Hot flushes (14% vs 9%) 3

• Endocrine abnormalities:

  • Hypothyroidism (8.1% vs 2.0%) 1, 3

• Gastrointestinal symptoms:

  • Diarrhea (20.3% vs 15.1%) 1, 3
  • Nausea (18.1% vs 15.8%) 1, 3

Serious Side Effects

Some less common but clinically important side effects include:

• Neurological effects:

  • Seizures (0.2% vs 0%) 1, 3
  • Mental impairment disorders (5.1% vs 3.0%) 1
  • Dizziness (9.3% vs 6.3%) 1

• Severe skin reactions:

  • Can be life-threatening in rare cases 3
  • May include blisters, peeling, and severe rash 3

• Cardiovascular events:

  • Heart disease, stroke, or mini-stroke 3
  • Can lead to death in rare cases 3

• Lung problems:

  • Inflammation of lungs (interstitial lung disease/pneumonitis) 3

Monitoring and Management

Baseline Assessment

• Thyroid function tests (TSH, free T4)
• DEXA scan for patients with osteoporosis risk factors
• Blood pressure assessment
• Evaluation for seizure risk and neurological disorders 1

During Treatment

• First 3 months:

  • Monitor for rash development
  • Assess thyroid function at 4-6 weeks
  • Monitor blood pressure 1

• Ongoing monitoring:

  • Regular thyroid function monitoring every 3-6 months
  • Fall risk assessment at each visit
  • Weight monitoring
  • Bone health assessment 1

Management of Specific Side Effects

1. Rash:

   • Early identification is critical
   • Topical treatments for mild cases
   • Temporary dose interruption for severe cases 1, 4
   • Patient education about skin care and early reporting of symptoms 4

2. Falls and Fractures:

   • Consider physical therapy referral
   • Home safety evaluation
   • Assessment for contributing factors like dizziness 1

3. Hypothyroidism:

   • Regular thyroid function monitoring
   • Thyroid replacement therapy when indicated 1

Impact on Treatment Continuation

• Overall, 10.6% of patients receiving apalutamide discontinued treatment due to adverse events compared to 7.0% with placebo 1
• The most common reason for discontinuation is rash (3.2%) 3
• Dose interruptions or reductions occurred in 33% of patients 3

Quality of Life Considerations

Despite the side effects, health-related quality of life was maintained in both apalutamide and placebo groups in clinical trials, suggesting that side effects can generally be managed without significant impact on overall quality of life 1, 2

Special Considerations

• Patients with known hypothyroidism require particularly careful thyroid function monitoring 1
• Patients with a history of seizures should avoid apalutamide 1, 3
• Patients with cardiovascular risk factors need close monitoring 1
• Drug interactions should be carefully evaluated before starting treatment 1, 5

By understanding and proactively managing these side effects, healthcare providers can help patients maintain treatment with apalutamide while minimizing adverse impacts on quality of life.