II. Indications

  1. Prostate Cancer (advanced, metastatic)
    1. Nonsteroidal Antiandrogens are typically used in combination with GnRH Agonist or surgical castration
    2. Augment GnRH Agonist effects, and counter their initial transient gonadotropin (LH, FSH) surge

III. Mechanism

  1. Nonsteroidal Antiandrogens bind and block androgen receptors
  2. Competitively block dihydrotestosterone, Testosterone and other androgen binding on Prostate Cancer cells

IV. Medications

  1. FIrst Generation Anti-androgens
    1. Bicalutamide (Casodex)
      1. Prostate Cancer: 50 mg orally daily (combined with GnRH Agonist)
    2. Flutamide (Eulexin)
      1. Prostate Cancer: 250 mg orally every 8 hours (combined with GnRH Agonist)
    3. Nilutamide (Nilandron)
      1. Prostate Cancer: 300 mg orally daily for 30 days, then 150 mg daily (starting with surgical castration)
  2. Second Generation Anti-androgens
    1. Precautions
      1. Second-Generation Anti-Androgens have many Drug Interactions
    2. Apalutamide (Erleada)
      1. Prostate Cancer: 240 mg orally daily (combined with GnRH Agonist or surgical castration)
    3. Darolutamide (Nubeqa)
      1. Prostate Cancer: 600 mg orally twice daily with food (combined with GnRH Agonist or surgical castration)
    4. Enzalutamide (Xtandi)
      1. Prostate Cancer: 160 mg orally daily with food (combined with GnRH Agonist or surgical castration)
    5. Proxalutamide

V. Adverse Effects: First Generation Anti-Androgens

  1. General anti-androgen effects (all agents)
    1. Hot Flashes
    2. Gynecomastia
    3. Impaired fertility
    4. Alopecia
  2. Hepatotoxicity (Bicalutamide, Flutamide, Nilutamide)
    1. Increased transaminases
    2. Liver failure
  3. Hematologic
    1. Methemoglobinemia (Flutamide)
    2. Hemolytic Anemia (Flutamide)
    3. Aplastic Anemia (Nilutamide)
  4. Pulmonary
    1. Interstitial Pneumonitis (Nilutamide, Bicalutamide)
  5. Other adverse effects
    1. Photosensitivity (Flutamide)
    2. Alcohol intolerance (Nilutamide)
    3. Cardiovascular Risk (Bicalutamide)
    4. Diarrhea

VI. Adverse Effects: Second Generation Anti-Androgens

  1. Bone effects
    1. Fall and Fracture risk (Apalutamide, Enzalutamide)
  2. Cardiovascular
    1. Posterior Reversible Encephalopathy Syndrome or PRES (Enzalutamide)
    2. Cardiovascular Risk (Apalutamide, Darolutamide, Enzalutamide)
  3. Neurologic
    1. Seizures (Apalutamide, Darolutamide, Enzalutamide)
  4. Dermatologic
    1. Severe skin reactions such as Stevens-Johnson Syndrome (Apalutamide)

VII. Safety

  1. Avoid in pregnancy
  2. Avoid in Lactation
  3. Monitoring
    1. Complete Blood Count
    2. Liver Function Tests

VIII. Drug Interactions

  1. Second-Generation Anti-Androgens have many Drug Interactions
  2. Warfarin
    1. Flutamide and Bicalutamide may increase INR

X. References

  1. (2022) Presc Lett, Medications to treat Prostate Cancer, Resource #380108

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Cost: Medications

bicalutamide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
BICALUTAMIDE 50 MG TABLET Generic $0.26 each