Side Effects of Nubeqa (Darolutamide)
The most common side effects of Nubeqa (darolutamide) include fatigue (12.1% vs 8.7% with placebo), pain in extremities (5.8% vs 3.2%), and rash (2.9% vs 0.9%), with relatively low incidence of fractures (4.2% vs 3.6%) compared to placebo. 1
Common Side Effects in Non-Metastatic CRPC
According to the FDA label and clinical guidelines, the most common side effects of darolutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) include:
- Increased liver function tests
- Decreased white blood cells (neutropenia)
- Fatigue
- Arm, leg, hand, or foot pain
- Rash 2
Common Side Effects When Combined with Docetaxel
When darolutamide is used in combination with docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC), additional side effects may include:
- Constipation
- Decreased appetite
- Bleeding
- Weight gain
- High blood pressure
- Decreased red blood cells (anemia)
- High blood sugar levels
- Low blood calcium levels 2
Serious Side Effects
The FDA label highlights two potential serious side effects that require monitoring:
Heart disease: Blockage of arteries in the heart (ischemic heart disease) that can lead to death has occurred in some patients. Seek immediate medical attention if you experience chest pain/discomfort or shortness of breath.
Seizures: Treatment with darolutamide may increase seizure risk. Patients should avoid activities where sudden loss of consciousness could cause serious harm. 2
Side Effect Profile Compared to Other Androgen Receptor Inhibitors
Darolutamide has a unique side effect profile compared to other androgen receptor inhibitors:
Lower CNS-related adverse events: Unlike enzalutamide which is associated with mental impairment disorders (5% vs 2% with placebo), darolutamide shows minimal penetration of the blood-brain barrier, resulting in fewer CNS-related side effects 1, 3
Cardiovascular events: While enzalutamide has been associated with major adverse cardiovascular events (5% vs 3% with placebo), darolutamide appears to have a relatively lower cardiovascular risk profile, though continued monitoring is warranted 1
Monitoring and Management
Patients taking darolutamide should:
- Have regular liver function tests
- Monitor for signs of heart problems
- Report any unusual symptoms promptly to healthcare providers
- Continue androgen deprivation therapy (ADT) as prescribed 2
Practical Considerations
- Take darolutamide exactly as prescribed, typically 600 mg (two 300 mg tablets) twice daily with food
- If a dose is missed, take it as soon as remembered before the next scheduled dose
- Do not take two doses together to make up for a missed dose
- Store at room temperature between 68°F to 77°F (20°C to 25°C) 2
The ARAMIS trial, which led to FDA approval of darolutamide for nmCRPC, demonstrated that darolutamide significantly improved metastasis-free survival compared to placebo (40.4 vs 18.4 months) with a manageable side effect profile. Grade 3 or 4 adverse events were reported in 24.7% of patients receiving darolutamide versus 19.5% with placebo 1.
When considering treatment options for prostate cancer, the side effect profile of darolutamide may be particularly favorable for patients with a history of seizures, brain injury, or those at risk for falls, given its minimal blood-brain barrier penetration.