What are the side effects of Enzalutamide (generic name for Xtandi)?

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Last updated: April 16, 2025View editorial policy

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From the Guidelines

Enzalutamide treatment is associated with several common side effects, including fatigue, hot flashes, diarrhea, and musculoskeletal pain, as well as less common but serious side effects such as seizures, falls with fractures, and cardiovascular events, as reported in the most recent study 1.

Common Side Effects

The most frequent side effects of enzalutamide include:

  • Fatigue, which can range from mild to severe
  • Hot flashes
  • Diarrhea
  • Musculoskeletal pain, including joint and muscle discomfort
  • Headache
  • Decreased appetite, leading to potential weight loss These side effects are well-documented in the literature, with the most recent study 1 confirming their prevalence.

Less Common but Serious Side Effects

Some patients may experience less common but more serious side effects, including:

  • High blood pressure, which requires regular monitoring
  • Neurological effects, such as dizziness, memory impairment, and seizures (particularly in those with a history of seizures or predisposing factors)
  • Sexual dysfunction, including reduced libido and erectile difficulties, due to the medication's mechanism of blocking androgen receptors
  • Laboratory abnormalities, such as anemia, neutropenia, and elevated liver enzymes, which necessitate periodic blood tests
  • Peripheral edema (swelling in extremities) and upper respiratory tract infections

Rare but Serious Side Effects

While rare, enzalutamide treatment can also lead to serious side effects, including:

  • Falls with fractures
  • Posterior reversible encephalopathy syndrome
  • Increased risk of cardiovascular events, particularly in those with pre-existing heart conditions These side effects are rare but can have significant consequences for patients, and their risk should be carefully considered when prescribing enzalutamide, as noted in the study 1.

From the FDA Drug Label

XTANDI may cause serious side effects including: • Seizure. • Posterior Reversible Encephalopathy Syndrome (PRES) • Allergic Reactions • Heart disease. • Falls and bone fractures • Swallowing problems or choking The most common side effects of XTANDI include: • muscle and joint pain • feeling more tired than usual • hot flashes • constipation • decreased appetite • diarrhea • high blood pressure • bleeding problems • falls • bone fractures • headache

The possible side effects of Enzalutamide (XTANDI) include:

  • Serious side effects:
    • Seizure
    • Posterior Reversible Encephalopathy Syndrome (PRES)
    • Allergic Reactions
    • Heart disease
    • Falls and bone fractures
    • Swallowing problems or choking
  • Common side effects:
    • Muscle and joint pain
    • Feeling more tired than usual
    • Hot flashes
    • Constipation
    • Decreased appetite
    • Diarrhea
    • High blood pressure
    • Bleeding problems
    • Falls
    • Bone fractures
    • Headache 2

From the Research

Side-Effects of Enzalutamide

  • Seizures: Enzalutamide has been associated with an increased risk of seizures, particularly in patients with a history of seizure or other predisposing factors 3.
  • Fatigue: Patient-reported fatigue is a common symptom in patients with prostate cancer, and enzalutamide has been shown to have a small increase in fatigue for the first 13-17 weeks after starting treatment, with fatigue stabilizing or improving thereafter 4.
  • Treatment-emergent adverse events: Common adverse events associated with enzalutamide include fatigue, asthenia, and back pain, with 84.4% of patients experiencing at least one treatment-emergent adverse event and 33.3% experiencing at least one serious treatment-emergent adverse event 3.
  • Laboratory findings and vital signs: Enzalutamide has been shown to have no clinically significant trends in abnormal laboratory findings, vital signs, or electrocardiograms 5.
  • Drug interactions: Enzalutamide is a moderate inducer of CYP2C9 and CYP2C19, and a strong inducer of CYP3A4, which can lead to interactions with other drugs that interact with these enzymes 6.

Specific Adverse Events

  • Seizure incidence: The incidence of confirmed seizure was 2.6 per 100 patient-years, with 1.1% of patients experiencing at least one confirmed seizure within 4 months of enzalutamide initiation 3.
  • Death: 9.0% of patients reported deaths during treatment or within 30 days of drug discontinuation, with 4 deaths considered possibly drug-related 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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