Can apalutamide cause nausea?

Apalutamide and Nausea

Yes, apalutamide can cause nausea, with clinical trials showing an incidence rate of 18.1% compared to 15.8% in placebo groups. 1

Incidence and Severity

Apalutamide (Erleada) is a nonsteroidal anti-androgen medication used primarily in the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). In the pivotal SPARTAN trial:

• Nausea occurred in 18.1% of patients receiving apalutamide versus 15.8% in the placebo group 1
• Nausea is not among the most severe or common side effects of apalutamide
• More common side effects include:
  • Fatigue (30.4%)
  • Hypertension (24.8%)
  • Rash (23.8%)
  • Diarrhea (20.3%)

Management of Apalutamide-Associated Nausea

For patients experiencing nausea while on apalutamide:

1. Assessment of nausea:

   • Rule out other causes of nausea (constipation, CNS pathology, hypercalcemia)
   • Determine severity and impact on quality of life

2. Pharmacologic management:

   • For patients with prior history of medication-induced nausea, prophylactic antiemetics are recommended 1
   • First-line agents:
     • Dopamine receptor antagonists (metoclopramide, haloperidol)
     • Benzodiazepines (prochlorperazine, thiethylperazine)
   • If nausea persists:
     • Add serotonin receptor antagonists (ondansetron, granisetron)
     • Consider corticosteroids which can be effective in combination with metoclopramide and ondansetron 1

3. Dosing strategy:

   • For persistent nausea, switch from as-needed to scheduled antiemetics for one week, then reassess 1
   • If nausea persists beyond one week, reassess the cause and consider medication changes

When to Consider Medication Changes

If nausea persists despite optimal antiemetic therapy for more than one week:

• Reassess for other causes of nausea
• Consider dose modification of apalutamide
• In severe cases, consider switching to an alternative androgen receptor signaling inhibitor (enzalutamide or darolutamide) 1

Monitoring Recommendations

• Regular assessment of nausea and other gastrointestinal symptoms during follow-up visits
• Proactive management of other common side effects that may occur concurrently:
  • Hypothyroidism (monitor TSH, especially in first 4-6 weeks) 2
  • Rash (early identification and management) 3
  • Fall risk and fracture prevention 2

Clinical Perspective

While nausea is a recognized side effect of apalutamide, it's generally not the most concerning or treatment-limiting adverse effect. The overall discontinuation rate due to adverse events in the SPARTAN trial was 10.6% for apalutamide versus 7.0% for placebo 1, suggesting that most side effects, including nausea, can be managed without necessitating treatment discontinuation.

Despite these side effects, studies have shown that health-related quality of life is generally maintained in patients receiving apalutamide 2, indicating that with proper management, patients can continue to benefit from this effective therapy while maintaining acceptable quality of life.