Nilutamide

{{Short description|Chemical compound}} {{Use dmy dates|date=April 2017}} {{Drugbox | Watchedfields = changed | verifiedrevid = 462261036 | IUPAC_name = 5,5-Dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione | image = Nilutamide.svg | image_class = skin-invert-image | width = 225px | image2 = Nilutamide molecule ball.png | image_class2 = bg-transparent | width2 = 225px

| pronounce = nye-LOO-tah-mide<ref name="LiverTox" /> | tradename = Nilandron, Anandron | Drugs.com = {{drugs.com|monograph|nilutamide}} | MedlinePlus = a697044 | pregnancy_US = C | pregnancy_US_comment = <ref>{{Cite web | url=https://www.drugs.com/pregnancy/nilutamide.html | title=Nilutamide (Nilandron) Use During Pregnancy | access-date=20 July 2016 | archive-date=28 October 2020 | archive-url=https://web.archive.org/web/20201028022327/https://www.drugs.com/pregnancy/nilutamide.html | url-status=live }}</ref> | legal_status = Rx-only | routes_of_administration = By mouth<ref name="PerryDoll2012" /> | class = Nonsteroidal antiandrogen

| bioavailability = Good<ref name="PerryDoll2012">{{cite book| vauthors = Perry MC, Doll DC, Freter CE |title=Perry's The Chemotherapy Source Book|url=https://books.google.com/books?id=My3SjQTguyYC&pg=PA711|date=30 July 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4698-0343-2|pages=711–}}</ref> | protein_bound = 80–84%<ref name="LemkeWilliams2012">{{cite book | vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1373|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=1373–}}</ref> | metabolism = Liver (CYP2C19, {{abbrlink|FMO|flavin-containing monooxygenase}})<ref name="PerryDoll2012" /><ref name="LemkeWilliams2012" /> | metabolites = At least 5, some active<ref name="LemkeWilliams2012" /><ref name="ChabnerLongo2010" /> | elimination_half-life = Mean: 56 hours (~2 days)<ref name="KolvenbagFurr2009">{{cite book | vauthors = Kolvenbag GJ, Furr BJ | chapter = Nonsteroidal Antiandrogens | pages = 347–368 | doi = 10.1007/978-1-59259-152-7_16 | title = Hormone Therapy in Breast and Prostate Cancer | veditors = Jordan VC, Furr HJ | year = 2009 | publisher = Humana Press | isbn = 978-1-60761-471-5 | quote = Although the t1/2 of nilutamide is h (mean 56 h) (39), suggesting that once-daily dosing would be appropriate, a three times per day regimen has been employed in most clinical trials.}}</ref><br />Range: 23–87 hours<ref name="KolvenbagFurr2009" /> | excretion = Urine: 62%<ref name="PerryDoll2012" /><ref name="LemkeWilliams2012" /><br />Feces: <10%<ref name="PerryDoll2012" /><ref name="LemkeWilliams2012" />

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 63612-50-0 | ATC_prefix = L02 | ATC_suffix = BB02 | ATC_supplemental = | PubChem = 4493 | IUPHAR_ligand = 2864 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00665 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4337 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 51G6I8B902 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00965 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 7573 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1274 | synonyms = RU-23908

| C=12 | H=10 | F=3 | N=3 | O=4 | SMILES = CC1(C(=O)N(C(=O)N1)C2=CC(=C(C=C2)[N+](=O)[O-])C(F)(F)F)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C12H10F3N3O4/c1-11(2)9(19)17(10(20)16-11)6-3-4-8(18(21)22)7(5-6)12(13,14)15/h3-5H,1-2H3,(H,16,20) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = XWXYUMMDTVBTOU-UHFFFAOYSA-N | melting_point = 149 }}  '''Nilutamide''', sold under the brand names '''Nilandron''' and '''Anandron''', is a nonsteroidal antiandrogen (NSAA) which is used in the treatment of prostate cancer.<ref>{{cite web |title=NILANDRON® (nilutamide) |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020169s008lbl.pdf |access-date=25 September 2018 |archive-date=30 March 2021 |archive-url=https://web.archive.org/web/20210330022054/https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020169s008lbl.pdf |url-status=dead }}</ref><ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA873|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=873–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA737|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=737–}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA199|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=199–}}</ref><ref name="Drugs.com">{{Cite web | url=https://www.drugs.com/international/nilutamide.html | title=Nilutamide | access-date=14 November 2017 | archive-date=2 December 2020 | archive-url=https://web.archive.org/web/20201202070855/https://www.drugs.com/international/nilutamide.html | url-status=live }}</ref><ref name="DenisGriffiths1999">{{cite book|vauthors=Denis LJ, Griffiths K, Kaisary AV, Murphy GP|title=Textbook of Prostate Cancer: Pathology, Diagnosis and Treatment: Pathology, Diagnosis and Treatment|url=https://books.google.com/books?id=GreZlojD-tYC&pg=PA280|date=1 March 1999|publisher=CRC Press|isbn=978-1-85317-422-3|pages=280–|access-date=21 February 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224045/https://books.google.com/books?id=GreZlojD-tYC&pg=PA280|url-status=live}}</ref> It has also been studied as a component of feminizing hormone therapy for transgender women and to treat acne and seborrhea in women.<ref name="Denis2012a"/><ref name="KreukelsSteensma2013" /><ref name="pmid2744186" /><ref name="pmid2462132" /> It is taken by mouth.<ref name="LemkeWilliams2012" />

Side effects in men include breast tenderness and enlargement, feminization, sexual dysfunction, and hot flashes.<ref name="pmid8997470">{{cite journal | vauthors = Dole EJ, Holdsworth MT | title = Nilutamide: an antiandrogen for the treatment of prostate cancer | journal = The Annals of Pharmacotherapy | volume = 31 | issue = 1 | pages = 65–75 | date = January 1997 | pmid = 8997470 | doi = 10.1177/106002809703100112 | s2cid = 20347526 }}</ref><ref name="Dart2004" /><ref name="MDMD2008" /><ref name="Lehne2013" /> Nausea, vomiting, visual disturbances, alcohol intolerance, elevated liver enzymes, and lung disease can occur in both sexes.<ref name="Lehne2013" /><ref name="Becker2001" /><ref name="Dart2004" /><ref name="WeinKavoussi2011" /><ref name="Jafri2014" /><ref name="BoarderNewby2010">{{cite book|vauthors=Boarder MR, Newby D, Navti P|title=Pharmacology for Pharmacy and the Health Sciences: A Patient-centred Approach|url=https://books.google.com/books?id=KVicAQAAQBAJ&pg=PA632|date=25 March 2010|publisher=OUP Oxford|isbn=978-0-19-955982-4|pages=632–|access-date=12 October 2016|archive-date=6 July 2024|archive-url=https://web.archive.org/web/20240706162108/https://books.google.com/books?id=KVicAQAAQBAJ&pg=PA632#v=onepage&q&f=false|url-status=live}}</ref> Rarely, nilutamide can cause respiratory failure and liver damage.<ref name="pmid8997470" /><ref name="Lehne2013" /> These unfavorable side effects, along with a number of associated cases of death, have limited the use of nilutamide.<ref name="DenisGriffiths1999" /><ref name="DeVitaLawrence2016">{{cite book| veditors = DeVita VT, Lawrence TS, Rosenberg SA |title=Prostate and Other Genitourinary Cancers: Cancer: Principles & Practice of Oncology|url=https://books.google.com/books?id=Bf3DCwAAQBAJ&pg=PT1006|date=18 March 2016|publisher=Wolters Kluwer Health|isbn=978-1-4963-5421-1|pages=1006–}}</ref><ref name="Chang2005" />

Nilutamide acts as a selective antagonist of the androgen receptor (AR), preventing the effects of androgens like testosterone and dihydrotestosterone (DHT) in the body.<ref name="SinghGauthier2000" /><ref name="Denis2012a" /> Because most prostate cancer cells rely on these hormones for growth and survival, nilutamide can slow the progression of prostate cancer and extend life in men with the disease.<ref name="Denis2012a" />

Nilutamide was discovered in 1977 and was first introduced for medical use in 1987.<ref name="Elks2014" /><ref name="LabrieLagacé1978" /><ref name="pmid385986" /><ref name="KolvenbagFurr2009" /> It became available in the United States in 1996.<ref name="Pavlik2012" /><ref name="BohlGao2005" /><ref name="AdisInsight" /> The drug has largely been replaced by newer and improved NSAAs, namely bicalutamide and enzalutamide, due to their better efficacy, tolerability, and safety, and is now rarely used.<ref name="Gulley2011" />

Nilutamide is a therapeutic alternative on the World Health Organization's List of Essential Medicines.<ref name="WHO24th">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines, 2025: WHO Model List of Essential Medicines, 24th list | year = 2025 | hdl = 10665/382243 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | doi = 10.2471/B09474 | hdl-access=free }}</ref>

==Medical uses==

===Prostate cancer=== Nilutamide is used in prostate cancer in combination with a gonadotropin-releasing hormone (GnRH) analogue at a dosage of 300 mg/day (150 mg twice daily) for the first 4 weeks of treatment, and 150 mg/day thereafter.<ref name="Chang2005"/><ref name="Upfal2006">{{cite book| vauthors = Upfal J |title=The Australian Drug Guide: Every Person's Guide to Prescription and Over-the-counter Medicines, Street Drugs, Vaccines, Vitamins and Minerals...|url=https://books.google.com/books?id=7O9kiqN2q2YC&pg=PA283|year=2006|publisher=Black Inc.|isbn=978-1-86395-174-6|pages=283–}}</ref> It is not indicated as a monotherapy in prostate cancer.<ref name="Chang2005" /> Only one small non-comparative study has assessed nilutamide as a monotherapy in prostate cancer.<ref name="pmid12603397">{{cite journal | vauthors = Anderson J | title = The role of antiandrogen monotherapy in the treatment of prostate cancer | journal = BJU International | volume = 91 | issue = 5 | pages = 455–461 | date = March 2003 | pmid = 12603397 | doi = 10.1046/j.1464-410X.2003.04026.x | quote = Trial experience with nilutamide monotherapy is limited to one small non-comparative study involving 26 patients with metastatic disease given nilutamide 100 mg three times daily (the dose used when nilutamide is administered as a component of MAB) [14]. The median progression-free survival in these patients was 9 months, with a median overall survival of 23 months. There have been no comparative trials of nilutamide with other antiandrogens or with castration [15]. The limited available data on nilutamide monotherapy means that no meaningful conclusions about the role of nilutamide in this setting can be determined. Nilutamide is not licensed as monotherapy. | s2cid = 8639102 | doi-access = }}</ref>

Nilutamide has been used to prevent the effects of the testosterone flare at the start of GnRH agonist therapy in men with prostate cancer.<ref name="pmid16986003">{{cite journal | vauthors = Thompson IM | title = Flare Associated with LHRH-Agonist Therapy | journal = Reviews in Urology | volume = 3 | issue = Suppl 3 | pages = S10–S14 | date = 2001 | pmid = 16986003 | pmc = 1476081 }}</ref><ref name="pmid8481213">{{cite journal | vauthors = Scaletscky R, Smith JA | title = Disease flare with gonadotrophin-releasing hormone (GnRH) analogues. How serious is it? | journal = Drug Safety | volume = 8 | issue = 4 | pages = 265–270 | date = April 1993 | pmid = 8481213 | doi = 10.2165/00002018-199308040-00001 | s2cid = 36964191 }}</ref><ref name="pmid2503723">{{cite journal | vauthors = Kuhn JM, Billebaud T, Navratil H, Moulonguet A, Fiet J, Grise P, Louis JF, Costa P, Husson JM, Dahan R | display-authors = 6 | title = Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide) | journal = The New England Journal of Medicine | volume = 321 | issue = 7 | pages = 413–418 | date = August 1989 | pmid = 2503723 | doi = 10.1056/NEJM198908173210701 }}</ref>

===Transgender hormone therapy=== Nilutamide has been studied for use as a component of feminizing hormone therapy for transgender women.<ref name="Denis2012a"/><ref name="KreukelsSteensma2013">{{cite book| vauthors = Kreukels BP, Steensma TD, De Vries AL |title= Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge|url=https://books.google.com/books?id=YQ5GAAAAQBAJ&pg=PA280|date=1 July 2013|publisher=Springer Science & Business Media|isbn=978-1-4614-7441-8|pages=280–}}</ref> It has been assessed in at least five small clinical studies for this purpose in treatment-naive subjects.<ref name="KreukelsSteensma2013" /><ref name="AsschemanGooren1989">{{cite journal | vauthors = Asscheman H, Gooren LJ, Peereboom-Wynia JD | title = Reduction in undesired sexual hair growth with anandron in male-to-female transsexuals--experiences with a novel androgen receptor blocker | journal = Clinical and Experimental Dermatology | volume = 14 | issue = 5 | pages = 361–363 | date = September 1989 | pmid = 2612040 | doi = 10.1111/j.1365-2230.1989.tb02585.x | s2cid = 45303518 }}</ref><ref name="Raode Voogt1988">{{cite journal | vauthors = Rao BR, de Voogt HJ, Geldof AA, Gooren LJ, Bouman FG | title = Merits and considerations in the use of anti-androgen | journal = Journal of Steroid Biochemistry | volume = 31 | issue = 4B | pages = 731–737 | date = October 1988 | pmid = 3143862 | doi = 10.1016/0022-4731(88)90024-6 }}</ref><ref name="van KemenadeCohen-Kettenis1989">{{cite journal | vauthors = van Kemenade JF, Cohen-Kettenis PT, Cohen L, Gooren LJ | title = Effects of the pure antiandrogen RU 23.903 (anandron) on sexuality, aggression, and mood in male-to-female transsexuals | journal = Archives of Sexual Behavior | volume = 18 | issue = 3 | pages = 217–228 | date = June 1989 | pmid = 2751416 | doi = 10.1007/BF01543196 | s2cid = 44664956 }}</ref><ref name="GoorenSpinder1987">{{cite journal | vauthors = Gooren L, Spinder T, Spijkstra JJ, van Kessel H, Smals A, Rao BR, Hoogslag M | title = Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 64 | issue = 4 | pages = 763–770 | date = April 1987 | pmid = 3102546 | doi = 10.1210/jcem-64-4-763 }}</ref><ref name="De VoogtRao1987">{{cite journal | vauthors = de Voogt HJ, Rao BR, Geldof AA, Gooren LJ, Bouman FG | title = Androgen action blockade does not result in reduction in size but changes histology of the normal human prostate | journal = The Prostate | volume = 11 | issue = 4 | pages = 305–311 | year = 1987 | pmid = 2960959 | doi = 10.1002/pros.2990110403 | s2cid = 84632739 }}</ref> In these studies, nilutamide monotherapy at a dosage of 300 mg/day, induced observable signs of clinical feminization in young transgender women (age range 19–33 years) within 8 weeks,<ref name="Raode Voogt1988" /> including breast development, decreased body hair (though not facial hair),<ref name="AsschemanGooren1989" /> decreased morning erections and sex drive,<ref name="van KemenadeCohen-Kettenis1989" /> and positive psychological and emotional changes.<ref name="van KemenadeCohen-Kettenis1989" /><ref name="Cohen-KettenisGooren1993">{{cite journal| vauthors = Cohen-Kettenis PT, Gooren LJ |title=The Influence of Hormone Treatment on Psychological Functioning of Transsexuals|journal=Journal of Psychology & Human Sexuality|volume=5|issue=4|year=1993|pages=55–67|issn=0890-7064|doi=10.1300/J056v05n04_04|s2cid=145237890 }}</ref> Signs of breast development occurred in all subjects within 6 weeks and were associated with increased nipple sensitivity,<ref name="De VoogtRao1987" /><ref name="Raode Voogt1988" /><ref name="van KemenadeCohen-Kettenis1989" /> and along with decreased hair growth, were the earliest sign of feminization.<ref name="Raode Voogt1988" />

Nilutamide did not change the size of the prostate gland (which is the same as with high-dosage cyproterone acetate and ethinylestradiol treatment for as long as 18 months), but was found to alter its histology, including increased stromal tissue with a significant reduction in acini and atrophic epithelial cells, indicating glandular atrophy.<ref name="GoorenSpinder1987" /><ref name="De VoogtRao1987" /><ref name="AdisInternational1993">{{cite book|title=Drugs & Aging|url=https://books.google.com/books?id=roFNAQAAIAAJ|year=1993|publisher=Adis International|quote=In 16 male subjects undergoing androgen blockade with nilutamide 100 to 300 mg/day for 8 weeks for male to female gender reassignment, prostate volume was not changed (de Voogt et al. 1987).|access-date=2 April 2018|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224014/https://books.google.com/books?id=roFNAQAAIAAJ|url-status=live}}</ref> In addition, readily apparent histological changes were observed in the testes, including a reduction in tubular and interstitial cells.<ref name="GoorenSpinder1987" />

Nilutamide was found to more than double luteinizing hormone (LH) and testosterone levels and to triple estradiol levels.<ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" /><ref name="GoorenSpinder1987" /> In contrast, follicle-stimulating hormone levels remained unchanged.<ref name="Raode Voogt1988" /><ref name="GoorenSpinder1987" /> A slight but significant increase in prolactin levels was observed, and levels of sex hormone-binding globulin increased as well.<ref name="Raode Voogt1988" /><ref name="GoorenSpinder1987" /> The addition of ethinylestradiol to nilutamide therapy after 8 weeks abolished the increase in LH, testosterone, and estradiol levels and dramatically suppressed testosterone levels, into the castrate range.<ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" /> Both nilutamide alone and the combination of nilutamide and estrogen were regarded as resulting in effective and favorable antiandrogen action and feminization in transgender women.<ref name="AsschemanGooren1989" /><ref name="Raode Voogt1988" />

===Skin conditions=== Nilutamide has been assessed in the treatment of acne and seborrhea in women in at least one small clinical study.<ref name="pmid2744186">{{cite journal | vauthors = Couzinet B, Thomas G, Thalabard JC, Brailly S, Schaison G | title = Effects of a pure antiandrogen on gonadotropin secretion in normal women and in polycystic ovarian disease | journal = Fertility and Sterility | volume = 52 | issue = 1 | pages = 42–50 | date = July 1989 | pmid = 2744186 | doi = 10.1016/s0015-0282(16)60786-0 | doi-access = }}</ref><ref name="pmid2462132">{{cite journal | vauthors = Namer M | title = Clinical applications of antiandrogens | journal = Journal of Steroid Biochemistry | volume = 31 | issue = 4B | pages = 719–729 | date = October 1988 | pmid = 2462132 | doi = 10.1016/0022-4731(88)90023-4 }}</ref> The dosage used was 200 mg/day, and in the study, "seborrhea and acne decreased markedly within the first month and practically disappeared after 2 months of [nilutamide] treatment."<ref name="pmid2744186" /><ref name="pmid2462132" />

===Available forms=== Nilutamide is available in the form of 50 and 150 mg oral tablets.<ref name="Meyers2018">{{cite book|vauthors=Meyers RA|title=Translational Medicine: Molecular Pharmacology and Drug Discovery|url=https://books.google.com/books?id=kuhPDwAAQBAJ&pg=PA46|date=2 March 2018|publisher=Wiley|isbn=978-3-527-68719-0|pages=46–|access-date=2 August 2018|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224026/https://books.google.com/books?id=kuhPDwAAQBAJ&pg=PA46|url-status=live}}</ref>

==Side effects== General side effects of NSAAs, including nilutamide, include gynecomastia, breast pain/tenderness, hot flashes (67%), depression, fatigue, sexual dysfunction (including loss of libido and erectile dysfunction), decreased muscle mass, and decreased bone mass with an associated increase in fractures.<ref name="Dart2004">{{cite book| vauthors = Dart RC |title=Medical Toxicology|url=https://books.google.com/books?id=BfdighlyGiwC&pg=PA521|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-2845-4|pages=521–}}</ref><ref name="MDMD2008">{{cite book|vauthors=DeAngelis LM, Posner JB|title=Neurologic Complications of Cancer|url=https://books.google.com/books?id=mpZ8Dp2KdHMC&pg=PA479|date=12 September 2008|publisher=Oxford University Press, USA|isbn=978-0-19-971055-3|pages=479–|access-date=21 February 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224047/https://books.google.com/books?id=mpZ8Dp2KdHMC&pg=PA479|url-status=live}}</ref><ref name="Lehne2013">{{cite book|vauthors=Lehne RA|title=Pharmacology for Nursing Care|url=https://books.google.com/books?id=_4SwO2dHcAIC&pg=PA1297|year=2013|publisher=Elsevier Health Sciences|isbn=978-1-4377-3582-6|pages=1297–|access-date=12 October 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224019/https://books.google.com/books?id=_4SwO2dHcAIC&pg=PA1297|url-status=live}}</ref> Also, nausea (24–27%), vomiting, constipation (20%), and insomnia (16%) may occur with nilutamide.<ref name="Lehne2013" /> Nilutamide monotherapy is known to eventually induce gynecomastia in 40 to 80% of men treated with it for prostate cancer, usually within 6 to 9 months of treatment initiation.<ref name="Bautista-VidalBarnoiu2014">{{cite journal | vauthors = Bautista-Vidal C, Barnoiu O, García-Galisteo E, Gómez-Lechuga P, Baena-González V | title = Treatment of gynecomastia in patients with prostate cancer and androgen deprivation | journal = Actas Urologicas Espanolas | volume = 38 | issue = 1 | pages = 34–40 | year = 2014 | pmid = 23850393 | doi = 10.1016/j.acuroe.2013.10.002 | quote = [...] the frequency of gynecomastia with antiandrogens in monotherapy is [...] around [...] 79% with nilutamide [...] }}</ref><ref name="DeepinderBraunstein2012">{{cite journal | vauthors = Deepinder F, Braunstein GD | title = Drug-induced gynecomastia: an evidence-based review | journal = Expert Opinion on Drug Safety | volume = 11 | issue = 5 | pages = 779–795 | date = September 2012 | pmid = 22862307 | doi = 10.1517/14740338.2012.712109 | quote = Treatment with estrogen has the highest incidence of gynecomastia, at 40 – 80%, anti-androgens, including flutamide, bicalutamide and nilutamide, are next, with a 40 – 70% incidence, followed by GnRH analogs (goserelin, leuprorelin) and combined androgen deprivation [...] | s2cid = 22938364 }}</ref><ref name="MichalopoulosKeshtgar2012">{{cite journal | vauthors = Michalopoulos NV, Keshtgar MR | title = Images in clinical medicine. Gynecomastia induced by prostate-cancer treatment | journal = The New England Journal of Medicine | volume = 367 | issue = 15 | pages = 1449 | date = October 2012 | pmid = 23050528 | doi = 10.1056/NEJMicm1209166 | quote = Gynecomastia occurs in up to 80% of patients who receive nonsteroidal antiandrogens (eg, bicalutamide, flutamide, or nilutamide), usually within the first 6 to 9 months after the initiation of treatment. }}</ref><ref name="pmid16321765">{{cite journal | vauthors = Di Lorenzo G, Autorino R, Perdonà S, De Placido S | title = Management of gynaecomastia in patients with prostate cancer: a systematic review | journal = The Lancet. Oncology | volume = 6 | issue = 12 | pages = 972–979 | date = December 2005 | pmid = 16321765 | doi = 10.1016/S1470-2045(05)70464-2 }}</ref>

Relative to other NSAAs, nilutamide has been uniquely associated with mild and reversible visual disturbances (31–58%) including delayed ocular adaptation to darkness and impaired color vision,<ref name="Becker2001">{{cite book|vauthors=Becker KL|title=Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1196|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=1196–|access-date=12 October 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110085133/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1196|url-status=live}}</ref> a disulfiram-like<ref name="Dart2004" /> alcohol intolerance (19%), interstitial pneumonitis (0.77–2.4%)<ref name="Gulley2011">{{cite book| vauthors = Gulley JL |title=Prostate Cancer|url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PT81|year=2011|publisher=Demos Medical Publishing|isbn=978-1-935281-91-7|pages=81–}}</ref><ref name="CamusIII2010">{{cite book| vauthors = Camus P, Rosenow III EC |title=Drug-induced and Iatrogenic Respiratory Disease|url=https://books.google.com/books?id=QlJsBgAAQBAJ&pg=PA235|date=29 October 2010|publisher=CRC Press|isbn=978-1-4441-2869-7|pages=235–}}</ref><ref name="Held-Warmkessel2006">{{cite book| vauthors = Held-Warmkessel J |title=Contemporary Issues in Prostate Cancer: A Nursing Perspective|url=https://books.google.com/books?id=dZe4ZSVDdBsC&pg=PA257|year=2006|publisher=Jones & Bartlett Learning|isbn=978-0-7637-3075-8|pages=257–}}</ref> (which can result in dyspnea (1%) as a secondary effect and can progress to pulmonary fibrosis),<ref name="WeinKavoussi2011">{{cite book|vauthors=Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA|author-link4=Alan W. Partin|title=Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set|url=https://books.google.com/books?id=fu3BBwAAQBAJ&pg=PA2939|date=25 August 2011|publisher=Elsevier Health Sciences|isbn=978-1-4160-6911-9|pages=2939–|access-date=21 February 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224041/https://books.google.com/books?id=fu3BBwAAQBAJ&pg=PA2939|url-status=live}}</ref> and hepatitis (1%), and has a higher incidence of nausea and vomiting compared to other NSAAs.<ref name="DenisGriffiths1999" /><ref name="Chang2005">{{cite book| vauthors = Chang C |title=Prostate Cancer: Basic Mechanisms and Therapeutic Approaches|url=https://books.google.com/books?id=4xQAr3Uh8EUC&pg=PA11|date=1 January 2005|publisher=World Scientific|isbn=978-981-256-920-2|pages=11–}}</ref><ref name="Lehne2013" /><ref name="RamonDenis2007">{{cite book| vauthors = Ramon J, Denis LJ |title=Prostate Cancer|url=https://books.google.com/books?id=Bg6ZbqhhboUC&pg=PA229|date=5 June 2007|publisher=Springer Science & Business Media|isbn=978-3-540-40901-4|pages=229–}}</ref> The incidence of interstitial pneumonitis with nilutamide has been found to be much higher in Japanese patients (12.6%), warranting particular caution in Asian individuals.<ref name="Mahler1996">{{cite book| vauthors = Mahler C |title=Antiandrogens in Prostate Cancer|chapter=A Review of the Clinical Studies with Nilutamide|year=1996|pages=105–111|doi=10.1007/978-3-642-45745-6_10|quote=Akaza had to prematurely terminate a nilutamide study in Japan as 12.6% of his patients developed interstitial lung disease [4]. This complication has been mainly observed in Japan and much less in other trials worldwide.|isbn=978-3-642-45747-0}}</ref><ref name="Micromedex2003">{{cite book|author=Micromedex|title=USP DI 2003: Drug Information for Healthcare Professionals|url=https://books.google.com/books?id=zEzWtsVl-KgC|date=1 January 2003|publisher=Thomson Micromedex|isbn=978-1-56363-429-1|pages=220–224|access-date=12 October 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224310/https://books.google.com/books?id=zEzWtsVl-KgC|url-status=live}}</ref> There is a case report of simultaneous liver and lung toxicity in a nilutamide-treated patient.<ref name="pmid1580304">{{cite journal | vauthors = Gomez JL, Dupont A, Cusan L, Tremblay M, Tremblay M, Labrie F | title = Simultaneous liver and lung toxicity related to the nonsteroidal antiandrogen nilutamide (Anandron): a case report | journal = The American Journal of Medicine | volume = 92 | issue = 5 | pages = 563–566 | date = May 1992 | pmid = 1580304 | doi = 10.1016/0002-9343(92)90756-2 }}</ref>

There is also a risk of hepatotoxicity with nilutamide, though occurrence is very rare and the risk is significantly less than with flutamide.<ref name="KolvenbagFurr2009" /><ref name="Aronson2009">{{cite book| vauthors = Aronson JK |title=Meyler's Side Effects of Endocrine and Metabolic Drugs|url=https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA150|date=21 February 2009|publisher=Elsevier|isbn=978-0-08-093292-7|pages=150–}}</ref> The incidence of abnormal liver function tests (e.g., elevated liver enzymes) has been variously reported as 2 to 33% with nilutamide.<ref name="pmid10388026" /><ref name="LiverTox" /> For comparison, the risk of elevated liver enzymes has been reported as 4 to 62% in the case of flutamide.<ref name="pmid10388026">{{cite journal | vauthors = McLeod DG | title = Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer | journal = The Oncologist | volume = 2 | issue = 1 | pages = 18–27 | date = 1997 | pmid = 10388026 | doi = 10.1634/theoncologist.2-1-18 | quote = Incidences of abnormal liver function test results have been variously reported from 2%-33% in nilutamide groups [13, 32, 33, 45] and from 4%-62% in flutamide groups [5, 7, 9, 11, 34, 38-40, 48] in trials of monotherapy and CAB. | doi-access = free }}</ref><ref name="Jafri2014">{{cite journal | vauthors = Hussain S, Haidar A, Bloom RE, Zayouna N, Piper MH, Jafri SM | title = Bicalutamide-induced hepatotoxicity: A rare adverse effect | journal = The American Journal of Case Reports | volume = 15 | pages = 266–270 | year = 2014 | pmid = 24967002 | pmc = 4068966 | doi = 10.12659/AJCR.890679 }}</ref><ref name="KolvenbagFurr2009" /> The risk of hepatotoxicity with nilutamide has been described as far less than with flutamide.<ref name="LiverTox">{{cite web | url = https://livertox.nih.gov/Nilutamide.htm | title = Nilutamide - LiverTox | website = National Institutes of Health | date = 2012 | pmid = 31643176 | access-date = 24 September 2018 | quote = In large registration clinical trials, ALT elevations occurred in 2% to 33% of patients during nilutamide therapy. The elevations were usually mild, asymptomatic and transient, rarely requiring drug discontinuation. In rare instances, clinically apparent acute liver injury has occurred during nilutamide therapy, but the number of published cases are few, and the agent appears to be far less hepatotoxic than flutamide. | archive-date = 24 September 2018 | archive-url = https://web.archive.org/web/20180924224717/https://livertox.nih.gov/Nilutamide.htm | url-status = dead }}</ref> Fulminant hepatic failure has been reported for nilutamide, with fatal outcome.<ref name="KolvenbagFurr2009" /><ref name="Aronson2011">{{cite book| vauthors = Aronson JK |title=Side Effects of Drugs Annual: A Worldwide Yearly Survey of New Data in Adverse Drug Reactions|url=https://books.google.com/books?id=zegpAgEt3CcC&pg=PA874|year=2011|publisher=Elsevier|isbn=978-0-444-53741-6|pages=874–}}</ref><ref name="pmid8977826">{{cite journal | vauthors = Marty F, Godart D, Doermann F, Mérillon H | title = [Fatal fulminating hepatitis caused by nilutamide. A new case] | language = fr | journal = Gastroenterologie Clinique et Biologique | volume = 20 | issue = 8–9 | pages = 710–711 | year = 1996 | pmid = 8977826 }}</ref><ref name="MerwatKabbani2008">{{cite journal | vauthors = Merwat SN, Kabbani W, Adler DG | title = Fulminant hepatic failure due to nilutamide hepatotoxicity | journal = Digestive Diseases and Sciences | volume = 54 | issue = 4 | pages = 910–913 | date = April 2009 | pmid = 18688719 | doi = 10.1007/s10620-008-0406-8 | quote = In addition, nilutamide is noted to exhibit mitochondrial toxicity by inhibiting complex I activity of the mitochondrial respiratory chain leading to the impairment of ATP formation and the biosynthesis of glutathione, thereby possibly predisposing the liver to toxicity [13]. | s2cid = 27421870 }}</ref> Between 1986 and 2003, the numbers of published cases of hepatotoxicity for antiandrogens totaled 46 for flutamide, 21 for cyproterone acetate, 4 for nilutamide, and 1 for bicalutamide.<ref name="ChitturiFarrell2013">{{cite book| vauthors = Chitturi S, Farrell GC |title=Drug-Induced Liver Disease|chapter=Adverse Effects of Hormones and Hormone Antagonists on the Liver|journal=Current Treatment Options in Gastroenterology|year=2013|volume=3|issue=6|pages=605–619|publisher=Academic Press |doi=10.1016/B978-0-12-387817-5.00033-9|pmid=11096606|quote=Liver injury is well recognized with all antiandrogens (Table 33-3). Thus, among all published cases identified between 1986 and 2003, flutamide (46), cyproterone (21), nilutamide (4), and bicalutamide (1) were implicated [107,108].|isbn=9780123878175}}</ref> Similarly to flutamide, nilutamide exhibits mitochondrial toxicity in hepatocytes by inhibiting respiratory complex I (NADH ubiquinone oxidoreductase) (though not respiratory complexes II, III, or IV) in the electron transport chain, resulting in reduced ATP and glutathione production and thus decreased hepatocyte survival.<ref name="MerwatKabbani2008" /><ref name="pmid8035313">{{cite journal | vauthors = Berson A, Schmets L, Fisch C, Fau D, Wolf C, Fromenty B, Deschamps D, Pessayre D | display-authors = 6 | title = Inhibition by nilutamide of the mitochondrial respiratory chain and ATP formation. Possible contribution to the adverse effects of this antiandrogen | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 270 | issue = 1 | pages = 167–176 | date = July 1994 | doi = 10.1016/S0022-3565(25)22351-5 | pmid = 8035313 }}</ref><ref name="CoeJia2007">{{cite journal | vauthors = Coe KJ, Jia Y, Ho HK, Rademacher P, Bammler TK, Beyer RP, Farin FM, Woodke L, Plymate SR, Fausto N, Nelson SD | display-authors = 6 | title = Comparison of the cytotoxicity of the nitroaromatic drug flutamide to its cyano analogue in the hepatocyte cell line TAMH: evidence for complex I inhibition and mitochondrial dysfunction using toxicogenomic screening | journal = Chemical Research in Toxicology | volume = 20 | issue = 9 | pages = 1277–1290 | date = September 2007 | pmid = 17702527 | pmc = 2802183 | doi = 10.1021/tx7001349 }}</ref> The nitro group of nilutamide has been theorized to be involved in both its hepatotoxicity and its pulmonary toxicity.<ref name="CoeJia2007"/><ref name="BoelsterliHo2006">{{cite journal | vauthors = Boelsterli UA, Ho HK, Zhou S, Leow KY | title = Bioactivation and hepatotoxicity of nitroaromatic drugs | journal = Current Drug Metabolism | volume = 7 | issue = 7 | pages = 715–727 | date = October 2006 | pmid = 17073576 | doi = 10.2174/138920006778520606 }}</ref>

{{Side effects of combined androgen blockade with nilutamide and surgical castration}}

{{Side effects of combined androgen blockade with nilutamide and a GnRH agonist}}

==Pharmacology==

===Pharmacodynamics===

====Antiandrogenic activity==== {{Affinities of selected androgen receptor ligands}}

Nilutamide acts as a selective competitive silent antagonist of the AR (IC<sub>50</sub> = 412 nM),<ref name="SinghGauthier2000">{{cite journal | vauthors = Singh SM, Gauthier S, Labrie F | title = Androgen receptor antagonists (antiandrogens): structure-activity relationships | journal = Current Medicinal Chemistry | volume = 7 | issue = 2 | pages = 211–247 | date = February 2000 | pmid = 10637363 | doi = 10.2174/0929867003375371 }}</ref> which prevents androgens like testosterone and DHT from activating the receptor.<ref name="Denis2012a">{{cite book| vauthors = Denis L |title=Antiandrogens in Prostate Cancer: A Key to Tailored Endocrine Treatment|url=https://books.google.com/books?id=jqZDBQAAQBAJ&pg=PT194|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-45745-6|pages=194–210}}</ref> The affinity of nilutamide for the AR is about 1 to 4% of that of testosterone and is similar to that of bicalutamide and 2-hydroxyflutamide.<ref name="Gaillard1996">{{cite book| vauthors = Gaillard M |title=Antiandrogens in Prostate Cancer|chapter=Pharmacodynamics and Pharmacokinetics of Nilutamide in Animal and Man|year=1996|pages=95–103|doi=10.1007/978-3-642-45745-6_9|isbn=978-3-642-45747-0}}</ref><ref name="FiggChau2010">{{cite book|vauthors=Figg W, Chau CH, Small EJ|title=Drug Management of Prostate Cancer|url=https://books.google.com/books?id=4KDrjeWA5-UC&pg=PA71|date=14 September 2010|publisher=Springer Science & Business Media|isbn=978-1-60327-829-4|pages=71–|access-date=12 October 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224030/https://books.google.com/books?id=4KDrjeWA5-UC&pg=PA71|url-status=live}}</ref><ref name="BenniVemer1990">{{cite book| vauthors = Benni HJ, Vemer HM |title=Chronic Hyperandrogenic Anovulation|url=https://books.google.com/books?id=q6zqFrCLUoIC&pg=PA153|date=15 December 1990|publisher=CRC Press|isbn=978-1-85070-322-8|pages=153–}}</ref> Similarly to 2-hydroxyflutamide, but unlike bicalutamide, nilutamide is able to weakly activate the AR at high concentrations.<ref name="FiggChau2010"/> It does not inhibit 5α-reductase.<ref name="pmid3331376">{{cite journal | vauthors = Raynaud JP, Fiet J, Le Goff JM, Martin PM, Moguilewsky M, Ojasoo T | title = Design of antiandrogens and their mechanisms of action: a case study (anandron) | journal = Hormone Research | volume = 28 | issue = 2–4 | pages = 230–241 | year = 1987 | pmid = 3331376 | doi = 10.1159/000180948 }}</ref>

Like other NSAAs such as flutamide and bicalutamide, nilutamide, without concomitant GnRH analogue therapy, increases serum androgen (by two-fold in the case of testosterone), estrogen, and prolactin levels due to inhibition of AR-mediated suppression of steroidogenesis via negative feedback on the hypothalamic–pituitary–gonadal axis.<ref name="Denis2012a" /> As such, though nilutamide is still effective as an antiandrogen as a monotherapy, it is given in combination with a GnRH analogue such as leuprorelin in prostate cancer to suppress androgen concentrations to castrate levels in order to attain maximal androgen blockade (MAB).<ref name="Denis2012a" />

Like flutamide and bicalutamide, nilutamide is able to cross the blood–brain barrier and has central antiandrogen actions.<ref name="pmid385986">{{cite journal | vauthors = Raynaud JP, Bonne C, Bouton MM, Lagace L, Labrie F | title = Action of a non-steroid anti-androgen, RU 23908, in peripheral and central tissues | journal = Journal of Steroid Biochemistry | volume = 11 | issue = 1A | pages = 93–99 | date = July 1979 | pmid = 385986 | doi = 10.1016/0022-4731(79)90281-4 }}</ref>

{{Relative affinities of first-generation nonsteroidal antiandrogens for the androgen receptor}}

====Cytochrome P450 inhibition==== Nilutamide is known to inhibit several cytochrome P450 enzymes, including CYP1A2, CYP2C9, and CYP3A4, and can result in increased levels of medications that are metabolized by these enzymes.<ref name="FerrandoLevenson2010">{{cite book| vauthors= Ferrando SJ, Levenson JL, Owen JA |title=Clinical Manual of Psychopharmacology in the Medically Ill|url=https://books.google.com/books?id=9b5NkWZ5k8wC&pg=PA256|date=20 May 2010|publisher=American Psychiatric Pub|isbn=978-1-58562-942-8|pages=256–}}</ref> It has also been found to inhibit the enzyme CYP17A1 (17α-hydroxylase/17,20-lyase) ''in vitro'' and thus the biosynthesis of androgens.<ref name="HarrisColeman1993">{{cite journal | vauthors = Harris MG, Coleman SG, Faulds D, Chrisp P | title = Nilutamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer | journal = Drugs & Aging | volume = 3 | issue = 1 | pages = 9–25 | year = 1993 | pmid = 8453188 | doi = 10.2165/00002512-199303010-00002 | s2cid = 262029302 }}</ref><ref name="pmid2956461">{{cite journal | vauthors = Ayub M, Levell MJ | title = Inhibition of rat testicular 17 alpha-hydroxylase and 17,20-lyase activities by anti-androgens (flutamide, hydroxyflutamide, RU23908, cyproterone acetate) in vitro | journal = Journal of Steroid Biochemistry | volume = 28 | issue = 1 | pages = 43–47 | date = July 1987 | pmid = 2956461 | doi = 10.1016/0022-4731(87)90122-1 }}</ref> However, nilutamide monotherapy significantly increases testosterone levels ''in vivo'', so the clinical significance of this finding is uncertain.<ref name="HarrisColeman1993" /><ref name="pmid2956461" />

===Pharmacokinetics=== Nilutamide has an elimination half-life of 23 to 87 hours, with a mean of 56 hours,<ref name="KolvenbagFurr2009" /> or about two days; this allows for once-daily administration.<ref name="DenisGriffiths1999" /> Steady state (plateau) levels of the drug are attained after two weeks of administration with a dosage of 150 mg twice daily (300 mg/day total).<ref name="Denis2012b">{{cite book| vauthors = Denis L |title=Antiandrogens in Prostate Cancer: A Key to Tailored Endocrine Treatment|url=https://books.google.com/books?id=jqZDBQAAQBAJ&pg=PT202|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-45745-6|pages=202–|quote=The plateau level of nilutamide (steady state) was obtained after about 14 days of repeated administration of the drug (150 mg b.i.d.) and did not depend upon intervals between doses.}}</ref> It is metabolized by CYP2C19, with at least five metabolites.<ref name="ChabnerLongo2010">{{cite book|vauthors=Chabner BA, Longo DL|title=Cancer Chemotherapy and Biotherapy: Principles and Practice|url=https://books.google.com/books?id=WL4arNFsQa8C&pg=PA680|date=8 November 2010|publisher=Lippincott Williams & Wilkins|isbn=978-1-60547-431-1|pages=680–|access-date=12 October 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110224032/https://books.google.com/books?id=WL4arNFsQa8C&pg=PA680|url-status=live}}</ref> Virtually all of the antiandrogenic activity of nilutamide comes from the parent drug (as opposed to metabolites).<ref name="MahlerVerhelst1998">{{cite journal | vauthors = Mahler C, Verhelst J, Denis L | title = Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer | journal = Clinical Pharmacokinetics | volume = 34 | issue = 5 | pages = 405–417 | date = May 1998 | pmid = 9592622 | doi = 10.2165/00003088-199834050-00005 | s2cid = 25200595 }}</ref>

==Chemistry== Nilutamide is structurally related to the first-generation NSAAs flutamide and bicalutamide as well as to the second-generation NSAAs enzalutamide and apalutamide.

==History== Nilutamide was developed by Roussel and was first described in 1977.<ref name="Elks2014" /><ref name="LabrieLagacé1978">{{cite journal| vauthors = Labrie F, Lagacé L, Ferland L, Kelly PA, Drouin J, Massicotte J, Bonne C, Raynaud JP, Dorrington JH | display-authors = 6 |title=Interactions Between LHRH, Sex Steroids and "Inhibin" in the Control of LH and FSH Secretion|journal=International Journal of Andrology|volume=1|issue=s2a|year=1978|pages=81–101|issn=0105-6263|doi=10.1111/j.1365-2605.1978.tb00008.x|doi-access=free}}</ref><ref name="pmid385986"/> It was first introduced for medical use in 1987 in France<ref name="KolvenbagFurr2009" /><ref name="FischerKlein2018">{{cite book| vauthors = Fischer J, Klein C, Childers WE |title=Successful Drug Discovery|url=https://books.google.com/books?id=t-JVDwAAQBAJ&pg=PA98|date=16 April 2018|publisher=Wiley|isbn=978-3-527-80868-7|pages=98–}}</ref> and was the second NSAA to be marketed, with flutamide preceding it and bicalutamide following it in 1995.<ref name="DenisGriffiths1999" /><ref>{{cite journal | vauthors = Wellington K, Keam SJ | title = Bicalutamide 150mg: a review of its use in the treatment of locally advanced prostate cancer | journal = Drugs | volume = 66 | issue = 6 | pages = 837–850 | year = 2006 | pmid = 16706554 | doi = 10.2165/00003495-200666060-00007 | s2cid = 46966712 }}</ref> It was not introduced until 1996 in the United States.<ref name="Pavlik2012">{{cite book| vauthors = Pavlik EJ |title=Estrogens, Progestins, and Their Antagonists: Health Issues|url=https://books.google.com/books?id=LAnpBwAAQBAJ&pg=PA167|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-4096-9|pages=167–}}</ref><ref name="BohlGao2005">{{cite journal | vauthors = Bohl CE, Gao W, Miller DD, Bell CE, Dalton JT | title = Structural basis for antagonism and resistance of bicalutamide in prostate cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 17 | pages = 6201–6206 | date = April 2005 | pmid = 15833816 | pmc = 1087923 | doi = 10.1073/pnas.0500381102 | doi-access = free | bibcode = 2005PNAS..102.6201B }}</ref><ref name="AdisInsight">{{Cite web | url=http://adisinsight.springer.com/drugs/800004379 | title=Nilutamide - AdisInsight | access-date=26 June 2017 | archive-date=5 May 2021 | archive-url=https://web.archive.org/web/20210505173834/https://adisinsight.springer.com/drugs/800004379 | url-status=live }}</ref>

==Society and culture==

===Generic names=== ''Nilutamide'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|DCF|Dénomination Commune Française}}.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Drugs.com" />

===Brand names=== Nilutamide is marketed under the brand name Nilandron in the United States and under the brand name Anandron elsewhere in the world such as in Australia, Canada, Europe, and Latin America.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

===Availability=== Nilutamide is or has been available in the United States, Canada, Australia, Europe, Latin America, Egypt, and Lebanon.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> In Europe, it is or has been available in Belgium, Croatia, the Czech Republic, Finland, France, the Netherlands, Norway, Poland, Portugal, Serbia, Sweden, Switzerland, and Yugoslavia.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> in Latin America, it is or has been available in Argentina, Brazil, and Mexico.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

==Research== The combination of an estrogen and nilutamide as a form of combined androgen blockade for the treatment of prostate cancer has been studied in animals.<ref name="pmid3420036">{{cite journal | vauthors = Rao BR, Geldof AA, van der Wilt CL, de Voogt HJ | title = Efficacy and advantages in the use of low doses of Anandron and estrogen combination in the treatment of prostate cancer | journal = The Prostate | volume = 13 | issue = 1 | pages = 69–78 | date = 1988 | pmid = 3420036 | doi = 10.1002/pros.2990130108 | s2cid = 23553575 }}</ref>

Nilutamide has been studied in the treatment of advanced breast cancer.<ref name="pmid25665553">{{cite journal | vauthors = Chia K, O'Brien M, Brown M, Lim E | title = Targeting the androgen receptor in breast cancer | journal = Current Oncology Reports | volume = 17 | issue = 2 | article-number = 4 | date = February 2015 | pmid = 25665553 | doi = 10.1007/s11912-014-0427-8 | s2cid = 5174768 | url = http://handle.unsw.edu.au/1959.4/61991 }}</ref><ref name="pmid1903951">{{cite journal | vauthors = Millward MJ, Cantwell BM, Dowsett M, Carmichael J, Harris AL | title = Phase II clinical and endocrine study of Anandron (RU-23908) in advanced post-menopausal breast cancer | journal = British Journal of Cancer | volume = 63 | issue = 5 | pages = 763–764 | date = May 1991 | pmid = 1903951 | pmc = 1972372 | doi = 10.1038/bjc.1991.170 }}</ref>

== References == {{Reflist}}

== Further reading == {{refbegin|30em}} * {{cite journal | vauthors = Raynaud JP, Bonne C, Moguilewsky M, Lefebvre FA, Bélanger A, Labrie F | title = The pure antiandrogen RU 23908 (Anandron), a candidate of choice for the combined antihormonal treatment of prostatic cancer: a review | journal = The Prostate | volume = 5 | issue = 3 | pages = 299–311 | year = 1984 | pmid = 6374639 | doi = 10.1002/pros.2990050307 | s2cid = 85417869 }} * {{cite journal | vauthors = Moguilewsky M, Bertagna C, Hucher M | title = Pharmacological and clinical studies of the antiandrogen Anandron | journal = Journal of Steroid Biochemistry | volume = 27 | issue = 4–6 | pages = 871–875 | year = 1987 | pmid = 3320565 | doi = 10.1016/0022-4731(87)90162-2 }} * {{cite journal | vauthors = Du Plessis DJ | title = Castration plus nilutamide vs castration plus placebo in advanced prostate cancer. A review | journal = Urology | volume = 37 | issue = 2 Suppl | pages = 20–24 | year = 1991 | pmid = 1992599 | doi = 10.1016/0090-4295(91)80097-q }} * {{cite journal | vauthors = Creaven PJ, Pendyala L, Tremblay D | title = Pharmacokinetics and metabolism of nilutamide | journal = Urology | volume = 37 | issue = 2 Suppl | pages = 13–19 | year = 1991 | pmid = 1992598 | doi = 10.1016/0090-4295(91)80096-p }} * {{cite journal | vauthors = Harris MG, Coleman SG, Faulds D, Chrisp P | title = Nilutamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer | journal = Drugs & Aging | volume = 3 | issue = 1 | pages = 9–25 | year = 1993 | pmid = 8453188 | doi = 10.2165/00002512-199303010-00002 | s2cid = 262029302 }} * {{cite journal | vauthors = Dole EJ, Holdsworth MT | title = Nilutamide: an antiandrogen for the treatment of prostate cancer | journal = The Annals of Pharmacotherapy | volume = 31 | issue = 1 | pages = 65–75 | date = January 1997 | pmid = 8997470 | doi = 10.1177/106002809703100112 | s2cid = 20347526 }} * {{cite journal | vauthors = Iversen P, Melezinek I, Schmidt A | title = Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function | journal = BJU International | volume = 87 | issue = 1 | pages = 47–56 | date = January 2001 | pmid = 11121992 | doi = 10.1046/j.1464-410x.2001.00988.x | s2cid = 28215804 | doi-access = free }} {{refend}}

Category:1-nitro-2-(trifluoromethyl)benzene derivatives Category:CYP1A1 inhibitors Category:CYP17A1 inhibitors Category:Disulfiram-like drugs Category:Hepatotoxins Category:Hormonal antineoplastic drugs Category:Hydantoins Category:Nonsteroidal antiandrogens Category:Progonadotropins Category:Prostate cancer Category:World Health Organization essential medicines