Side Effects of Erleada (Apalutamide)
Erleada (apalutamide) has several significant side effects including fatigue (30.4%), rash (23.8%), falls (15.6%), weight loss (16.1%), arthralgia (15.9%), and fractures (11.7%), which require proactive monitoring and management to minimize their impact on patients.
Common Side Effects (>15% incidence)
Apalutamide causes several common adverse events at significantly higher rates than placebo when added to androgen deprivation therapy (ADT) 1:
- Fatigue: 30.4% (vs 21.1% with placebo)
- Hypertension: 24.8% (vs 19.8%)
- Rash: 23.8% (vs 5.5%)
- Diarrhea: 20.3% (vs 15.1%)
- Nausea: 18.1% (vs 15.8%)
- Weight loss: 16.1% (vs 6.3%)
- Arthralgia: 15.9% (vs 7.5%)
- Falls: 15.6% (vs 9.0%)
Less Common but Significant Side Effects
Several less common but clinically important side effects include 1, 2, 3:
- Fractures: 11.7% (vs 6.5%)
- Dizziness: 9.3% (vs 6.3%)
- Hypothyroidism: 8.1% (vs 2.0%)
- Mental impairment disorders: 5.1% (vs 3.0%)
- Seizures: 0.2% (vs 0%)
Serious Adverse Events
The FDA label highlights several serious adverse events that require special attention 3:
- Heart disease, stroke, or mini-stroke: Bleeding in the brain or blockage of arteries in the heart or brain have occurred and can lead to death
- Fractures and falls: Apalutamide can weaken bones and muscles, increasing risk for falls and fractures
- Seizures: Treatment may increase seizure risk; patients should avoid activities where sudden loss of consciousness could cause harm
- Severe skin reactions: Can lead to death or be life-threatening; requires immediate medical attention if severe rash, fever, lymph node swelling, or blistering occurs
- Lung problems (ILD/pneumonitis): Can be fatal or life-threatening; requires monitoring for new/worsening respiratory symptoms
Monitoring and Management Recommendations
Before Starting Treatment
- Baseline thyroid function tests (TSH, free T4)
- Baseline DEXA scan for patients with osteoporosis risk factors
- Baseline blood pressure assessment
- Evaluate for seizure risk and history of neurological disorders
During First 3 Months
- Monitor for rash development (highest risk in first few months)
- Assess thyroid function at 4-6 weeks
- Monitor blood pressure
- Evaluate for falls risk
Ongoing Monitoring
- Regular thyroid function monitoring every 3-6 months 2
- Fall risk assessment at each visit
- Weight monitoring
- Bone health assessment
Management of Specific Side Effects
Rash Management
- Typically appears early in treatment
- May require topical treatments or temporary dose interruption in severe cases
- If severe cutaneous adverse reaction (SCAR) is suspected, interrupt treatment until etiology is determined 3
Hypothyroidism Management
- Generally grade 1 or 2
- Usually identified early after starting treatment
- May require thyroid replacement therapy 2
Fall and Fracture Risk Management
- Consider physical therapy referral
- Home safety evaluation
- Assessment for contributing factors like dizziness
- Consider bone-protective agents when appropriate 2
Treatment Discontinuation
Overall, 10.6% of patients receiving apalutamide discontinued treatment due to adverse events compared to 7.0% of patients receiving placebo 1, 4. This indicates a slightly higher discontinuation rate that clinicians should be aware of when initiating treatment.
Quality of Life Impact
Despite these side effects, health-related quality of life was maintained in both apalutamide and placebo groups in the SPARTAN trial 2, suggesting that while side effects occur more frequently with apalutamide, they can generally be managed without significant impact on overall quality of life.
Special Considerations
- Patients with known hypothyroidism require particularly careful monitoring of thyroid function 1
- Patients with history of seizures should avoid apalutamide 3
- Patients with cardiovascular risk factors need close monitoring for cardiovascular events 3
- Drug interactions should be carefully evaluated before starting treatment 5