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

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

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

Ontology: Flutamide (C0016384)

Definition (NCI) A toluidine derivative and a nonsteroidal antiandrogen that is structurally related to bicalutamide and nilutamide. Flutamide and its more potent active metabolite 2-hydroxyflutamide competitively block dihydrotestosterone binding at androgen receptors, forming inactive complexes which cannot translocate into the cell nucleus. Formation of inactive receptors inhibits androgen-dependent DNA and protein synthesis, resulting in tumor cell growth arrest or transient tumor regression. (NCI04)
Definition (NCI_NCI-GLOSS) An anticancer drug that is a type of antiandrogen.
Definition (MSH) An antiandrogen with about the same potency as cyproterone in rodent and canine species.
Definition (PDQ) A toluidine derivative and nonsteroidal antiandrogen that is structurally related to bicalutamide and nilutamide. Flutamide and its more potent active metabolite 2-hydroxyflutamide competitively block dihydrotestosterone binding at androgen receptors, forming inactive complexes which cannot translocate into the cell nucleus. Formation of inactive receptors inhibits androgen-dependent DNA and protein synthesis, resulting in tumor cell growth arrest or transient tumor regression. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39811&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39811&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C509" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D005485
SnomedCT 387587007, 96371003
English Flutamide, Niftolid, Niftolide, Propanamide, 2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)-, 2-Methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide, 4'-Nitro-3'-trifluoromethylisobutyranilide, Alpha,alpha,alpha-trifluoro-2-methy-4'-nitro-m-propionotoluidide, flutamide, flutamide (medication), FLUTAMIDE, Flutamide [Chemical/Ingredient], Flutamide (product), Flutamide (substance), FLUT
Swedish Flutamid
Czech flutamid
Finnish Flutamidi
Russian FLUTAMID, SCH 13521, ФЛУТАМИД
Italian Niftolid, Flutamide
Polish Flutamid
Japanese ニフトリド, フルタミド
Spanish flutamida (producto), flutamida (sustancia), flutamida, Flutamida, Niftolida
French Flutamide
German Flutamid, Niftolid
Portuguese Flutamida, Niftolida

Ontology: nilutamide (C0068771)

Definition (NCI_NCI-GLOSS) A drug that blocks the effects of male hormones in the body. It is a type of antiandrogen.
Definition (NCI) A synthetic, nonsteroidal agent with antiandrogenic properties. Nilutamide preferentially binds to androgen receptors and blocks androgen receptor activation by testosterone and other androgens; this agent may inhibit androgen-dependent growth of normal and neoplastic prostate cells. (NCI04)
Definition (PDQ) A synthetic, nonsteroidal agent with antiandrogenic properties. Nilutamide preferentially binds to androgen receptors and blocks androgen receptor activation by testosterone and other androgens; this agent may inhibit androgen-dependent growth of normal and neoplastic prostate cells. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40450&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40450&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1173" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C021277
SnomedCT 96372005, 404866003
English 2,4-Imidazolidinedione, 5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)-, 5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)- 2,4-imidazolidinedione, nilutamide, 5,5-Dimethyl-3-[4-nitro-3-(trifluoro-methyl)phenyl]-2,4-imidazolidinedione, 1-(3'-Trifluoromethyl-4'-nitrophenyl)-4,4-dimethylimidazoline-3,5-dione, nilutamide (medication), nilutamide [Chemical/Ingredient], Nilutamide, Nilutamide (substance), Nilutamide (product), ANAN, NILUTAMIDE
Spanish nilutamida (sustancia), nilutamida, nilutamida (producto)

Ontology: bicalutamide (C0285590)

Definition (NCI_NCI-GLOSS) An anticancer drug that belongs to the family of drugs called antiandrogens.
Definition (NCI) A synthetic, nonsteroidal antiandrogen. Bicalutamide competitively binds to cytosolic androgen receptors in target tissues, thereby inhibiting the receptor binding of androgens. This agent does not bind to most mutated forms of androgen receptors. (NCI04)
Definition (PDQ) A synthetic, nonsteroidal antiandrogen. Bicalutamide competitively binds to cytosolic androgen receptors in target tissues, thereby inhibiting the receptor binding of androgens. This agent does not bind to most mutated forms of androgen receptors. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41298&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41298&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1599" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C053541
SnomedCT 391846005, 108766001, 386908000
English 4'-cyano-3-(4-fluorophenylsulfonyl)-2-hydroxy-2-methyl-3'-(trifluoromethyl)propionanilide, Propanamide, N-(4-cyano-3-(trifluoromethyl)phenyl)-3-((4-fluorophenyl)sulfonyl)-2-hydroxy-2-methyl-, (+-)-, bicalutamide, 4'-Cyano-alpha,alpha,alpha-trifuloro-3-[(p-fluorophenyl)sulfonyl]-2-methyl-m-lactotoluidide, 4-Cyano-3-trifluoromethyl-N-(3-p-fluorophenylsulfonyl-2-hydroxy-2-methylpropionyl)aniline, N-[4-Cyano-3-(trifluoromethyl)phenyl]3-3[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-propanamide, (+/-)-N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide, bicalutamide (medication), BICALUTAMIDE, bicalutamide [Chemical/Ingredient], Bicalutamide - chemical, Bicalutamide - chemical (substance), Bicalutamide, Bicalutamide (product), Bicalutamide (substance), CDX
Spanish bicalutamida (producto), bicalutamida (sustancia), bicalutamida

Ontology: Synthetic antiandrogen (C0521962)

Concepts Pharmacologic Substance (T121) , Hormone (T125) , Organic Chemical (T109)
SnomedCT 96369003, 418702005
Spanish antiandrógeno sintético (sustancia), antiandrógeno sintético (producto), antiandrógeno sintético
English Synthetic antiandrogen (product), Synthetic antiandrogen, Synthetic antiandrogen, NOS, Synthetic antiandrogen (substance)

Ontology: Nonsteroidal Anti-Androgens (C1320169)

Definition (MSH) Nonsteroidal agents which block the action or downregulate the synthesis of ANDROGENS.
Concepts Organic Chemical (T109)
MSH D057466
SnomedCT 406777002
English Nonsteroidal Antiandrogens, AntiAndrogens, Nonsteroidal, Anti-Androgens, Nonsteroidal, Nonsteroidal Anti Androgens, Nonsteroidal Anti-Androgens, Nonsteroidal antiandrogen (substance), Nonsteroidal antiandrogen
French Anti-androgènes non stéroïdiens, Antiandrogènes non stéroïdiens
German Antiandrogene, nichtsteroidale, Nichtsteroidale Antiandrogene
Czech nesteroidní antiandrogeny
Italian Antiandrogeni non steroidei
Spanish Antiandrógenos no Esteroides, antiandrógeno no esteroide (sustancia), antiandrógeno no esteroide
Russian АНТИ-АНДРОГЕНЫ НЕСТЕРОИДНЫЕ, NESTEROIDNYE ANTIANDROGENY, НЕСТЕРОИДНЫЕ АНТИАНДРОГЕНЫ, ANTI-ANDROGENY NESTEROIDNYE
Polish Antyandrogeny niesteroidowe
Norwegian Ikke-steroide antiandrogener, Antiandrogener, ikke-steroide
Portuguese Antiandrógenos não Esteroidais, Drogas Antiandrogênicas não Esteroidais

Ontology: Androgen Receptor Antagonists (C2936804)

Definition (MSH) Compounds that bind to and inhibit the activation of ANDROGEN RECEPTORS.
Concepts Pharmacologic Substance (T121)
MSH D059002
English Receptor Antagonists, Androgen, Antagonists, Androgen Receptor, Androgen Receptor Antagonists
French Antagonistes du récepteur androgénique, Antagonistes du récepteur aux androgènes, Antagonistes du récepteur des androgènes
German Androgenrezeptor-Antagonisten, Androgenrezeptorantagonisten
Czech receptory androgenů - antagonisté
Italian Antagonisti per i recettori degli androgeni
Spanish Antagonistas de Receptores Androgénicos, Antagonistas de Receptores de Andrógenos
Russian АНДРОГЕННЫХ РЕЦЕПТОРОВ АНТАГОНИСТЫ, ANDROGENNYKH RETSEPTOROV ANTAGONISTY
Portuguese Antagonistas de Receptores de Andrógenos, Antagonistas de Receptores de Androgênios
Polish Antagoniści receptora androgenowego, Antagoniści receptora androgenu, Blokery receptora androgenu
Norwegian Androgenreseptorantagonister

Ontology: enzalutamide (C3496793)

Definition (NCI) An orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. Through a mechanism that is reported to be different from other approved AR antagonists, enzalutamide inhibits the activity of prostate cancer cell ARs, which may result in a reduction in prostate cancer cell proliferation and, correspondingly, a reduction in the serum prostate specific antigen (PSA) level. AR over-expression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C540278
SnomedCT 703125003, 703684000
English enzalutamide, ENZALUTAMIDE, Benzamide, 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxo-1-imidazolidinyl)-2-fluoro-N-methyl-, enzalutamide (medication), chemotherapeutics enzalutamide, Enzalutamide, Enzalutamide (substance), Enzalutamide (product)