View source for Bicalutamide

{{Short description|Antiandrogen medication}}
{{Use dmy dates|date=December 2016}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 459978482
| drug_name = 
| INN = 
| type = <!-- empty -->
| image = Bicalutamide.svg
| image_class = skin-invert-image
| width = 250
| alt = 
| image2 = Bicalutamide 3D ball.png
| image_class2 = bg-transparent
| width2 = 250
| alt2 = 
| caption =

<!-- Clinical data -->
| pronounce = Bicalutamide:<br />• {{IPAc-en|ˌ|b|aɪ|k|ə|ˈ|l|uː|t|ə|m|aɪ|d}}<ref name="(PharmD.)Clark2009">{{cite book | vauthors = Finkel R, Clark MA, Cubeddu LX |title=Pharmacology |url=https://books.google.com/books?id=Q4hG2gRhy7oC&pg=PA481 |year=2009 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-7155-9 |pages=481–}}</ref><br />• {{respell|BY|kə|LOO|tə|myde}}<ref name="(PharmD.)Clark2009" />
| tradename = Casodex, Calutex, others
| Drugs.com = {{drugs.com|monograph|bicalutamide}}
| MedlinePlus = a697047
| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->
| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->
| DailyMedID = Bicalutamide
| licence_US = Bicalutamide
| pregnancy_AU = D
| pregnancy_AU_comment = 
| pregnancy_category= 
| dependency_liability = 
| addiction_liability = 
| routes_of_administration = [[Oral administration|By mouth]]<ref name="Cockshott2004" />
| class = [[Nonsteroidal antiandrogen]]
| ATCvet = 
| ATC_prefix = L02
| ATC_suffix = BB03
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment = 
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = 
| legal_US = Rx-only
| legal_US_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability = Well-absorbed; [[Bioavailability#Absolute bioavailability|absolute bioavailability]] unknown<ref name="Dart2004" />
| protein_bound = [[Racemic mixture|Racemate]]: 96.1%<ref name="Cockshott2004" /><br />[[Enantiomer|(''R'')-Isomer]]: 99.6%<ref name="Cockshott2004" /><br />(Mainly to [[human serum albumin|albumin]])<ref name="Cockshott2004" />
| metabolism = [[Liver]] (extensively):<ref name="LemkeWilliams2008">{{cite book | vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry |url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1288 |year=2008 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-6879-5 |pages=121, 1288, 1290 |url-status=live |archive-url=https://web.archive.org/web/20170908145128/https://books.google.com/books?id=R0W1ErpsQpkC |archive-date=8 September 2017 |df=dmy-all}}</ref><ref name="GrosseCampeau2013" /><br />• [[Hydroxylation]] ([[CYP3A4]])<br />• [[Glucuronidation]] ([[UGT1A9]])
| metabolites = • Bicalutamide glucuronide<br />• Hydroxybicalutamide<br />• Hydroxybicalutamide {{abbr|gluc.|glucuronide}}<br />(All inactive)<ref name="LemkeWilliams2008" /><ref name="Cockshott2004">{{cite journal |vauthors=Cockshott ID |title=Bicalutamide: clinical pharmacokinetics and metabolism |journal=Clinical Pharmacokinetics |volume=43 |issue=13 |pages=855–878 |date=2004 |pmid=15509184 |doi=10.2165/00003088-200443130-00003|s2cid=29912565 }}</ref><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 |year=1997 |pmid=8997470 |doi=10.1177/106002809703100112 |s2cid=20347526 |quote=page 67: Currently, information is not available regarding the activity of the major urinary metabolites of bicalutamide, bicalutamide glucuronide, and hydroxybicalutamide glucuronide.}}</ref><ref name="Schellhammer2005">{{cite journal |vauthors=Schellhammer PF |title=An evaluation of bicalutamide in the treatment of prostate cancer |journal=Expert Opinion on Pharmacotherapy |volume=3 |issue=9 |pages=1313–28 |date=September 2002 |pmid=12186624 |doi=10.1517/14656566.3.9.1313 |s2cid=32216411 |quote=The clearance of bicalutamide occurs pre- dominantly by hepatic metabolism and glucuronidation, with excretion of the resulting inactive metabolites in the urine and faces.}}</ref>
<!-- | onset = Unknown<ref name="Skidmore-Roth2015">{{cite book | vauthors = Skidmore-Roth L |title=Mosby's Drug Guide for Nursing Students, with 2016 Update |url=https://books.google.com/books?id=g_BwCgAAQBAJ&pg=PA117 |date=16 July 2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-17297-4 |pages=117–}}</ref> -->
| elimination_half-life = Single-dose: 5.8 days<ref name="Skidmore-Roth2013" /><br />Continuous: 7–10 days<ref name="JordanFurr2010" />
<!-- | duration_of_action = Unknown<ref name="Skidmore-Roth2015" /> -->
| excretion = [[Feces]]: 43%<ref name="LemkeWilliams2008" /><br />[[Urine]]: 34%<ref name="LemkeWilliams2008" />

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 90357-06-5
| CAS_supplemental = <br />[http://www.commonchemistry.org/ChemicalDetail.aspx?ref=113299-40-4 113299-40-4] ((''R'')-isomer)<br />[http://www.commonchemistry.org/ChemicalDetail.aspx?ref=113299-38-0 113299-38-0] ((''S'')-isomer)
| PubChem = 2375
| IUPHAR_ligand = 2863
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01128
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2284
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = A0Z3NAU9DP
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C08160
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 91617
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 409
| NIAID_ChemDB = 
| PDB_ligand = 198
| synonyms = ICI-176,334; ZD-176,334

<!-- Chemical data -->
| IUPAC_name = (''RS'')-''N''-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide
| C=18 | H=14 | F=4 | N=2 | O=4 | S=1
| chirality = [[Racemic mixture]] (of (''R'')- and (''S'')-[[enantiomer]]s)
| SMILES = CC(O)(CS(=O)(=O)c1ccc(F)cc1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
| Jmol = 
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H14F4N2O4S/c1-17(26,10-29(27,28)14-6-3-12(19)4-7-14)16(25)24-13-5-2-11(9-23)15(8-13)18(20,21)22/h2-8,26H,10H2,1H3,(H,24,25)
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LKJPYSCBVHEWIU-UHFFFAOYSA-N

<!-- Physical data -->
| density = 
| density_notes = 
| melting_point = 191
| melting_high = 193
| melting_notes = (experimental)
| boiling_point = 650
| boiling_notes = (predicted)
| solubility = 0.005
| sol_units = 
| specific_rotation = 
}}
<!-- Definition and medical uses -->
'''Bicalutamide''', sold under the brand name '''Casodex''' among others, is an [[antiandrogen]] medication that is primarily used to treat [[prostate cancer]].<ref name=AHFS2016>{{cite web |title=Bicalutamide |url=https://www.drugs.com/monograph/bicalutamide.html |publisher=The American Society of Health-System Pharmacists |access-date=8 December 2016 |url-status=live |archive-url=https://web.archive.org/web/20161229173027/https://www.drugs.com/monograph/bicalutamide.html |archive-date=29 December 2016 |df=dmy-all}}</ref> It is typically used together with a [[gonadotropin-releasing hormone analogue|gonadotropin-releasing hormone (GnRH) analogue]] or [[orchiectomy|surgical removal of the testicles]] to treat [[metastatic prostate cancer]] (mPC).<ref name=WassStewart2011>{{cite book | vauthors = Wass JA, Stewart PM |title=Oxford Textbook of Endocrinology and Diabetes |url=https://books.google.com/books?id=9R-RAAAAQBAJ&pg=PA1625 |date=28 July 2011 |publisher=OUP Oxford |isbn=978-0-19-923529-2 |pages=1625–|url-status=live |archive-url=https://web.archive.org/web/20160511132922/https://books.google.com/books?id=9R-RAAAAQBAJ&pg=PA1625 |archive-date=11 May 2016 |df=dmy-all}}</ref><ref name=AHFS2016/><ref name="ShergillArya2010">{{cite book | vauthors = Shergill I, Arya M, Grange PR, Mundy AR |title=Medical Therapy in Urology |date=2010 |publisher=Springer Science & Business Media |isbn=9781848827042 |page=40 |url=https://books.google.com/books?id=QmCBTQpHWaUC&pg=PA40 |language=en |url-status=live |archive-url=https://web.archive.org/web/20141028071604/http://books.google.com/books?id=QmCBTQpHWaUC |archive-date=28 October 2014 |df=dmy-all}}</ref> To a lesser extent, it is used at high doses for [[locally advanced prostate cancer]] (LAPC) as a monotherapy without [[castration]].<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="Wellington2006" /> Bicalutamide was also previously used as monotherapy to treat [[localized prostate cancer]] (LPC), but authorization for this use was withdrawn following unfavorable trial findings.<ref name="Wellington2006" /><ref name="pmid18093474" /><ref name="BowsherCarter2008" /><ref name="NargundRaghavan2015" /> Besides prostate cancer, bicalutamide is limitedly used in the treatment of [[hirsutism|excessive hair growth]] and [[scalp hair loss]] in women,<ref name=WilliamsBigby2009>{{cite book | vauthors = Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B |title=Evidence-Based Dermatology |url=https://books.google.com/books?id=SbsQij5xkfYC&pg=PA529 |date=22 January 2009 |publisher=John Wiley & Sons |isbn=978-1-4443-0017-8 |pages=529–|url-status=live |archive-url=https://web.archive.org/web/20160502212533/https://books.google.com/books?id=SbsQij5xkfYC&pg=PA529 |archive-date=2 May 2016 |df=dmy-all}}</ref><ref name="pmid35032336">{{cite journal | vauthors = Carvalho RM, Santos LD, Ramos PM, Machado CJ, Acioly P, Frattini SC, Barcaui CB, Donda AL, Melo DF | title = Bicalutamide and the new perspectives for female pattern hair loss treatment: What dermatologists should know | journal = J Cosmet Dermatol | volume = 21| issue = 10| pages = 4171–4175| date = January 2022 | pmid = 35032336 | doi = 10.1111/jocd.14773 | s2cid = 253239337 | url = }}</ref> as a [[puberty blocker]] and component of [[feminizing hormone therapy]] for [[transgender youth|transgender girls]] and [[transgender women|women]],<ref name="pmid30256230">{{cite journal | vauthors = Randolph JF | title = Gender-Affirming Hormone Therapy for Transgender Females | journal = Clin Obstet Gynecol | volume = 61 | issue = 4 | pages = 705–721 | date = December 2018 | pmid = 30256230 | doi = 10.1097/GRF.0000000000000396 | s2cid = 52821192 }}</ref> to treat [[gonadotropin-independent precocious puberty|gonadotropin-independent early puberty]] in boys,<ref name=JamesonGroot2015>{{cite book | vauthors = Jameson JL, De Groot LJ |title=Edndocrinology: Adult and Pediatric |url=https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA2425 |date=25 February 2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-32195-2 |pages=2425–2426, 2139}}</ref> and to prevent [[priapism|overly long-lasting erections]] in men.<ref name=YuanDeSouza2008>{{cite journal |vauthors=Yuan J, Desouza R, Westney OL, Wang R |title=Insights of priapism mechanism and rationale treatment for recurrent priapism |journal=Asian Journal of Andrology |volume=10 |issue=1 |pages=88–101 |year=2008 |pmid=18087648 |doi=10.1111/j.1745-7262.2008.00314.x|doi-access=free }}</ref> It is taken [[oral administration|by mouth]].<ref name=AHFS2016 />

<!-- Side effects -->
Common [[side effect]]s of bicalutamide in men include [[gynecomastia|breast growth]], [[breast pain|breast tenderness]], and [[hot flashes]].<ref name=AHFS2016 /> Other side effects in men include [[feminization (biology)|feminization]] and [[sexual dysfunction]].<ref name="pmid20626600">{{cite journal |vauthors=Elliott S, Latini DM, Walker LM, Wassersug R, Robinson JW |title=Androgen deprivation therapy for prostate cancer: recommendations to improve patient and partner quality of life |journal=The Journal of Sexual Medicine |volume=7 |issue=9 |pages=2996–3010 |year=2010 |pmid=20626600 |doi=10.1111/j.1743-6109.2010.01902.x }}</ref><ref name="HammererManka2019">{{cite book | title = Urologic Oncology | vauthors = Hammerer P, Manka L | chapter = Androgen Deprivation Therapy for Advanced Prostate Cancer | date = 2019 | pages = 255–276 | publisher = Springer International Publishing | doi = 10.1007/978-3-319-42623-5_77 | isbn = 978-3-319-42622-8 | url = | quote = Bicalutamide is the most widely used antiandrogen in the treatment of prostate cancer. [...] Common side effects [of bicalutamide] include breast enlargement, breast tenderness, hot flashes, and constipation as well as feminization and changes in mood and liver as well as lung toxicity; monitoring of liver enzymes is recommended during treatment (Schellhammer and Davis 2004).}}</ref> Some side effects like breast changes and feminization are minimal when combined with castration.<ref name="DrozAudisio2012">{{cite book | vauthors = Droz J, Audisio RA |title=Management of Urological Cancers in Older People |url=https://books.google.com/books?id=-P2wi-xVk_gC&pg=PA84 |date=2 October 2012 |publisher=Springer Science & Business Media |isbn=978-0-85729-986-4 |pages=84– |url-status=live |archive-url=https://web.archive.org/web/20160511211354/https://books.google.com/books?id=-P2wi-xVk_gC&pg=PA84 |archive-date=11 May 2016 |df=dmy-all}}</ref> While the medication appears to produce few side effects in women, its use in women is not explicitly approved by the [[Food and Drug Administration]] (FDA) at this time.<ref name="Shapiro2012">{{cite book | vauthors = Shapiro J |title=Hair Disorders: Current Concepts in Pathophysiology, Diagnosis and Management, An Issue of Dermatologic Clinics |url=https://books.google.com/books?id=9rLeICotHEoC&pg=PT187 |date=12 November 2012 |publisher=Elsevier Health Sciences |isbn=978-1-4557-7169-1 |pages=187–}}</ref><ref name=AHFS2016/> Use during [[pregnancy]] may harm the [[fetus|baby]].<ref name=AHFS2016 /> In men with [[early prostate cancer]], bicalutamide monotherapy has been found to increase the [[mortality rate|likelihood of death]] from causes other than prostate cancer.<ref name="pmid35569476" /><ref name="Wellington2006" /> Bicalutamide produces [[elevated transaminases|abnormal liver changes]] necessitating [[drug discontinuation|discontinuation]] in around 1% of people.<ref name="FDALabel">{{cite web | title=Casodex- bicalutamide tablet | website=DailyMed | date=1 September 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dfee4fe7-8478-4a3e-925d-00be3cd0ab67 | access-date=7 May 2020 | archive-date=27 July 2020 | archive-url=https://web.archive.org/web/20200727174111/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dfee4fe7-8478-4a3e-925d-00be3cd0ab67 | url-status=live }}</ref><ref name=Wellington2006>{{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=837–50 |year=2006 |pmid=16706554 |doi=10.2165/00003495-200666060-00007 |s2cid=46966712 |url=http://www.antialabs.com/reference/21018026.pdf |url-status=dead |archive-url=https://web.archive.org/web/20160828024232/http://www.antialabs.com/reference/21018026.pdf |archive-date=28 August 2016 |df=dmy-all |access-date=13 August 2016 }}</ref> Rarely, it has been associated with cases of serious [[hepatotoxicity|liver damage]],<ref name=AHFS2016 /> serious [[pulmonary toxicity|lung toxicity]],<ref name=Dart2004 /> and [[photosensitivity|sensitivity to light]].<ref name="LeeOda2016">{{cite journal |vauthors=Lee K, Oda Y, Sakaguchi M, Yamamoto A, Nishigori C |title=Drug-induced photosensitivity to bicalutamide – case report and review of the literature |journal=Photodermatology, Photoimmunology & Photomedicine |volume=32 |issue=3 |pages=161–4 |date=May 2016 |pmid=26663090 |doi=10.1111/phpp.12230|s2cid=2761388 }}</ref><ref name="ReactionsWeekly2016">{{cite journal |vauthors=Lee K, etal |title=Drug-induced photosensitivity to bicalutamide – case report and review of the literature |journal=Reactions Weekly |volume=1612 |issue=1 |year=2016 |pages=161–4 |doi=10.1007/s40278-016-19790-1|pmid=26663090 |s2cid=261402820 }}</ref> Although the risk of adverse liver changes is small, [[liver function tests|monitoring of liver function]] is recommended during treatment.<ref name=AHFS2016 />

<!-- Mechanism of action -->
Bicalutamide is a member of the [[nonsteroidal antiandrogen]] (NSAA) group of medications.<ref name=Dart2004>{{cite book | vauthors = Dart RC |title=Medical Toxicology |url=https://books.google.com/books?id=BfdighlyGiwC&pg=PA497 |year=2004 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2845-4 |pages=497, 521 |url-status=live |archive-url=https://web.archive.org/web/20160511213240/https://books.google.com/books?id=BfdighlyGiwC&pg=PA497 |archive-date=11 May 2016 |df=dmy-all}}</ref> It works by [[binding selectivity|selectively]] [[receptor antagonist|blocking]] the [[androgen receptor]] (AR), the [[biological target]] of the [[androgen]] [[sex hormone]]s [[testosterone]] and [[dihydrotestosterone]] (DHT).<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=211–47 |date=February 2000 |pmid=10637363 |doi=10.2174/0929867003375371}}</ref> It does not lower androgen levels.<ref name=Dart2004 /> The medication can have some [[estrogen (medication)|estrogen]]-like effects in men when used as a monotherapy due to increased [[estradiol]] levels.<ref name="IIIBarbieri2013a">{{cite book |vauthors=Strauss III JF, Barbieri RL |title=Yen & Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management |url=https://books.google.com/books?id=TTCwAAAAQBAJ&pg=PA688 |date=28 August 2013 |publisher=Elsevier Health Sciences |isbn=978-1-4557-5972-9 |pages=688– |quote=Bone density improves in men receiving bicalutamide, most likely secondary to the 146% increase in estradiol and the fact that estradiol is the major mediator of bone density in men. |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143128/https://books.google.com/books?id=TTCwAAAAQBAJ&pg=PA688 |url-status=live }}</ref><ref name="MarcusFeldman2007" /><ref name="MahlerVerhelst1998" /> Bicalutamide is [[absorption (pharmacokinetics)|well-absorbed]], and its absorption is not affected by food.<ref name=Cockshott2004 /> The [[elimination half-life]] of the medication is around one week.<ref name="Cockshott2004" /><ref name=AHFS2016 /> It shows [[peripheral selectivity]] in animals, but crosses the [[blood–brain barrier]] and affects both the body and brain in humans.<ref name=Cockshott2004 /><ref name="FurrTucker1996"/>

<!-- History, society, and culture -->
Bicalutamide was patented in 1982 and approved for medical use in 1995.<ref name=FischerGanellin2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=515 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA515 |language=en |access-date=24 August 2017 |archive-date=12 January 2023 |archive-url=https://web.archive.org/web/20230112173145/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA515 |url-status=live }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Bicalutamide is available as a [[generic medication]].<ref name=Ric2015>{{cite book | vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition |date=2015 |publisher=Jones & Bartlett Learning |isbn=9781284057560 |page=381}}</ref> The drug is sold in more than 80&nbsp;countries, including most [[developed countries]].<ref name="Drugs.com-2">{{cite web |title=Bicalutamide – International Drug Names |url=https://www.drugs.com/international/bicalutamide.html |publisher=Drugs.com |access-date=13 August 2016 |url-status=live |archive-url=https://web.archive.org/web/20160918143637/https://www.drugs.com/international/bicalutamide.html |archive-date=18 September 2016 |df=dmy-all}}</ref><ref name=Ak1999>{{cite journal |vauthors=Akaza H |title=[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer—basic clinical aspects] |language=ja |journal=Gan to Kagaku Ryoho. Cancer & Chemotherapy |volume=26 |issue=8 |pages=1201–7 |year=1999 |pmid=10431591 }}</ref><ref name="AstraZeneca1999">{{cite web |title=1999 Annual Report and Form 20-F |url=https://ddd.uab.cat/pub/infanu/40172/iaASTZENa1999ieng.pdf |publisher=AstraZeneca |access-date=1 July 2017 |archive-date=9 September 2017 |archive-url=https://web.archive.org/web/20170909052202/https://ddd.uab.cat/pub/infanu/40172/iaASTZENa1999ieng.pdf |url-status=live }}</ref> It was at one time the most widely used antiandrogen in the treatment of prostate cancer, with millions of men with the disease having been prescribed it.<ref name="HammererManka2019" /><ref name=MukherjiPezaro2012>{{cite journal |vauthors=Mukherji D, Pezaro CJ, De-Bono JS |title=MDV3100 for the treatment of prostate cancer |journal=Expert Opinion on Investigational Drugs |volume=21 |issue=2 |pages=227–33 |date=February 2012 |pmid=22229405 |doi=10.1517/13543784.2012.651125|s2cid=46339544 }}</ref><ref name=PchejetskiAlshaker2014>{{cite journal |vauthors=Pchejetski D, Alshaker H, Stebbing J |title=Castrate-resistant prostate cancer: the future of antiandrogens |journal=Trends in Urology & Men's Health |volume=5 |issue=1 |year=2014 |pages=7–10 |doi=10.1002/tre.371 |s2cid=57988002 |url=https://ueaeprints.uea.ac.uk/61989/1/Accepted_manuscript.pdf |doi-access=free |access-date=11 December 2019 |archive-date=19 July 2018 |archive-url=https://web.archive.org/web/20180719060234/https://ueaeprints.uea.ac.uk/61989/1/Accepted_manuscript.pdf |url-status=live }}</ref><ref name="Campbell2014">{{cite web | vauthors = Campbell T |title=Slowing Sales for Johnson & Johnson's Zytiga May Be Good News for Medivation |publisher=The Motley Fool |date=22 January 2014 |access-date=20 July 2016 |url=http://www.fool.com/investing/general/2014/01/22/slowing-sales-for-johnson-johnsons-zytiga-may-be-g.aspx |quote=[...] the most commonly prescribed treatment for metastatic castration resistant prostate cancer: bicalutamide. That was sold as AstraZeneca's billion-dollar-a-year drug Casodex before losing patent protection in 2008. AstraZeneca still generates a few hundred million dollars in sales from Casodex, [...] |url-status=live |archive-url=https://web.archive.org/web/20160826161537/http://www.fool.com/investing/general/2014/01/22/slowing-sales-for-johnson-johnsons-zytiga-may-be-g.aspx |archive-date=26 August 2016 |df=dmy-all}}</ref><ref name=HHS2010>{{citation |title=Bicalutamide BPCA Drug Use Review in the Pediatric Population | vauthors = Chang S |publisher=[[United States Department of Health and Human Services|U.S. Department of Health and Human Service]] |date=10 March 2010 |access-date=20 July 2016 |url=https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM214400.pdf |url-status=dead |archive-url=https://web.archive.org/web/20161024181831/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM214400.pdf |archive-date=24 October 2016 |df=dmy-all}}</ref> Although bicalutamide is also used for other indications besides prostate cancer, the vast majority of prescriptions appear to be for treatment of prostate cancer.<ref name="HHS2010" />

{{TOC limit|3}}

==Medical uses==
{{Main|Medical uses of bicalutamide}}

Bicalutamide is [[approved drug|approved]] for and mainly used in the following indications:<ref name="BagatellBremner2003" />

* [[Metastatic prostate cancer]] (mPC) in men in combination with a [[gonadotropin-releasing hormone]] (GnRH) [[gonadotropin-releasing hormone analogue|analogue]] or [[orchiectomy|surgical castration]] at 50&nbsp;mg/day<ref name="FDALabel" /><ref name="LemkeWilliams2008" /><ref name="pmid15882477">{{cite journal |vauthors=Klotz L, Schellhammer P |title=Combined androgen blockade: the case for bicalutamide |journal=Clinical Prostate Cancer |volume=3 |issue=4 |pages=215–9 |date=March 2005 |pmid=15882477 |doi=10.3816/cgc.2005.n.002}}</ref>
* [[Locally advanced prostate cancer]] (LAPC) in men as a monotherapy at 150&nbsp;mg/day (not approved for this use in the United States)<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="Wellington2006" /><ref name="pmid9301693">{{cite journal |vauthors=Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ |title=Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group |journal=Urology |volume=50 |issue=3 |pages=330–6 |date=September 1997 |pmid=9301693 |doi=10.1016/S0090-4295(97)00279-3}}</ref>

In Japan, bicalutamide is uniquely used at a dosage of 80&nbsp;mg/day both in combination with castration and as a monotherapy in the treatment of prostate cancer.<ref name="SuzukiKamiya2008" /><ref name="pmid17199134" />

Bicalutamide is also employed for the following [[off-label use|off-label]] (non-approved) indications:

* To reduce the effects of the testosterone flare at the initiation of [[gonadotropin-releasing hormone agonist|{{abbr|GnRH|gonadotropin-releasing hormone}} agonist]] therapy in men<ref name="Melmed2016" /><ref name="SugionoWinkler2005">{{cite journal |vauthors=Sugiono M, Winkler MH, Okeke AA, Benney M, Gillatt DA |title=Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer—a pilot study |journal=Prostate Cancer and Prostatic Diseases |volume=8 |issue=1 |pages=91–4 |year=2005 |pmid=15711607 |doi=10.1038/sj.pcan.4500784|doi-access=free }}</ref>
* [[Androgen-dependent condition|Androgen-dependent]] [[cutaneous condition|skin]] and [[hair disease|hair conditions]] such as [[acne]], [[seborrhea]], [[hirsutism|excessive hair growth]], and [[pattern hair loss|scalp hair loss]] in women as well as [[hyperandrogenism|high testosterone levels]] due to [[polycystic ovary syndrome]] (PCOS) in women, at 25 to 50&nbsp;mg/day generally in combination with a [[oral contraceptive|birth control pill]]<ref name="WilliamsBigby2009" /><ref name="pmid24455796">{{cite journal |vauthors=Erem C |title=Update on idiopathic hirsutism: diagnosis and treatment |journal=Acta Clinica Belgica |volume=68 |issue=4 |pages=268–74 |year=2013 |pmid=24455796 |doi=10.2143/ACB.3267|s2cid=39120534 }}</ref><ref name="AscensoMarques2009">{{cite journal |vauthors=Ascenso A, Marques HC |title=Acne in the adult |journal=Mini Reviews in Medicinal Chemistry |volume=9 |issue=1 |pages=1–10 |date=January 2009 |pmid=19149656 |doi=10.2174/138955709787001730}}</ref><ref name="pmid27512185">{{cite journal |vauthors=Kaur S, Verma P, Sangwan A, Dayal S, Jain VK |title=Etiopathogenesis and Therapeutic Approach to Adult Onset Acne |journal=Indian Journal of Dermatology |volume=61 |issue=4 |pages=403–7 |year=2016 |pmid=27512185 |pmc=4966398 |doi=10.4103/0019-5154.185703 |doi-access=free }}</ref><ref name="LottiMaggi2015">{{cite book | vauthors = Lotti F, Maggi M |title=European Handbook of Dermatological Treatments |chapter=Hormonal Treatment for Skin Androgen-Related Disorders |year=2015 |pages=1451–1464 |publisher=Springer |doi=10.1007/978-3-662-45139-7_142 |isbn=978-3-662-45138-0 }}</ref><ref name="MüderrisÖner2009">{{cite journal | vauthors = Müderris II, Öner G | title = Hirsutizm Tedavisinde Flutamid ve Bikalutamid Kullanımı | trans-title = Flutamide and Bicalutamide Treatment in Hirsutism | journal = Turkiye Klinikleri Journal of Endocrinology-Special Topics | volume = 2 | issue = 2 | date = 2009 | pages = 110–2 | language = tr | issn = 1304-0529 | url = http://www.turkiyeklinikleri.com/article/en-hirsutizm-tedavisinde-flutamid-ve-bikalutamid-kullanimi-55753.html | access-date = 28 March 2019 | archive-date = 27 July 2020 | archive-url = https://web.archive.org/web/20200727004948/http://www.turkiyeklinikleri.com/article/en-hirsutizm-tedavisinde-flutamid-ve-bikalutamid-kullanimi-55753.html | url-status = live }}</ref><ref name="pmid29211888" />
* [[Feminizing hormone therapy]] for [[transgender women]] usually at 50&nbsp;mg/day in combination with an [[estrogen (medication)|estrogen]].<ref name="pmid30256230" /><ref name="FishmanPaliou2019">{{cite book| vauthors = Fishman SL, Paliou M, Poretsky L, Hembree WC |title=Transgender Medicine|chapter=Endocrine Care of Transgender Adults|year=2019|pages=143–163|issn=2523-3785|doi=10.1007/978-3-030-05683-4_8|series=Contemporary Endocrinology|publisher=Springer |isbn=978-3-030-05682-7|s2cid=86772102}}</ref><ref name="pmid30612811">{{cite journal | vauthors = Neyman A, Fuqua JS, Eugster EA | title = Bicalutamide as an Androgen Blocker With Secondary Effect of Promoting Feminization in Male-to-Female Transgender Adolescents | journal = The Journal of Adolescent Health | volume = 64 | issue = 4 | pages = 544–546 | date = April 2019 | pmid = 30612811 | pmc = 6431559 | doi = 10.1016/j.jadohealth.2018.10.296 }}</ref><ref name=Gooren2011>{{cite journal | vauthors = Gooren LJ | title = Clinical practice. Care of transsexual persons | journal = The New England Journal of Medicine | volume = 364 | issue = 13 | pages = 1251–1257 | date = March 2011 | pmid = 21449788 | doi = 10.1056/nejmcp1008161 }}</ref><ref name="Deutsch2016">{{cite book |vauthors=Deutsch M |title=Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People |date=17 June 2016 |edition=2nd |publisher=Center of Excellence for Transgender Health |location=University of California, San Francisco |page=28 |url=https://transcare.ucsf.edu/sites/transcare.ucsf.edu/files/Transgender-PGACG-6-17-16.pdf |access-date=9 June 2023 |archive-date=30 May 2023 |archive-url=https://web.archive.org/web/20230530050124/https://transcare.ucsf.edu/sites/transcare.ucsf.edu/files/Transgender-PGACG-6-17-16.pdf |url-status=live }}</ref><ref name="Vincent2018">{{cite book|vauthors=Vincent B|title=Transgender Health: A Practitioner's Guide to Binary and Non-Binary Trans Patient Care|url=https://books.google.com/books?id=k_RMDwAAQBAJ&pg=PA158|date=21 June 2018|publisher=Jessica Kingsley Publishers|isbn=978-1-78450-475-5|pages=158–|access-date=1 January 2019|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114143128/https://books.google.com/books?id=k_RMDwAAQBAJ&pg=PA158|url-status=live}}</ref><ref name="WierckxGooren2014">{{cite journal | vauthors = Wierckx K, Gooren L, T'Sjoen G | title = Clinical review: Breast development in trans women receiving cross-sex hormones | journal = The Journal of Sexual Medicine | volume = 11 | issue = 5 | pages = 1240–1247 | date = May 2014 | pmid = 24618412 | doi = 10.1111/jsm.12487 }}</ref>
* [[Peripheral precocious puberty]] in boys at 12.5 to 100&nbsp;mg/day in combination with an [[aromatase inhibitor]] like [[anastrozole]], especially for [[familial male-limited precocious puberty]] (testotoxicosis)<ref name="FDALabel" /><ref name="SchoelwerEugster2015">{{cite book | vauthors = Schoelwer M, Eugster EA | title = Puberty from Bench to Clinic | chapter = Treatment of Peripheral Precocious Puberty | volume = 29 | pages = 230–239 | year = 2015 | pmid = 26680582 | pmc = 5345994 | doi = 10.1159/000438895 | isbn = 978-3-318-02788-4 | series = Endocrine Development }}</ref><ref name="HaddadEugster2019">{{cite journal | vauthors = Haddad NG, Eugster EA | title = Peripheral precocious puberty including congenital adrenal hyperplasia: causes, consequences, management and outcomes | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 33 | issue = 3 | article-number = 101273 | date = June 2019 | pmid = 31027974 | doi = 10.1016/j.beem.2019.04.007 | hdl-access = free | s2cid = 135410503 | hdl = 1805/19111 }}</ref><ref name="HaddadEugster2012">{{cite book| vauthors = Haddad NG, Eugster EA |title=Handbook of Growth and Growth Monitoring in Health and Disease|chapter=Peripheral Precocious Puberty: Interventions to Improve Growth|year=2012|pages=1199–1212|publisher=Springer |doi=10.1007/978-1-4419-1795-9_71|isbn=978-1-4419-1794-2}}</ref><ref name="pmid31144045">{{cite book| vauthors = Zacharin M |title=Pediatric Pharmacotherapy|chapter=Disorders of Puberty: Pharmacotherapeutic Strategies for Management|year=2019|issn=0171-2004|pmid=31144045|doi=10.1007/164_2019_208|series=Handbook of Experimental Pharmacology|volume=261|pages=507–538|publisher=Springer |isbn=978-3-030-50493-9|s2cid=169040406}}</ref><ref name="KliegmanStanton2015">{{cite book |vauthors=Kliegman RM, Stanton B, St Geme J, Schor NF |title=Nelson Textbook of Pediatrics |url=https://books.google.com/books?id=P9piCAAAQBAJ&pg=PA2661 |date=17 April 2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-26352-8 |pages=2661– |access-date=27 September 2016 |archive-date=12 January 2023 |archive-url=https://web.archive.org/web/20230112011925/https://books.google.com/books?id=P9piCAAAQBAJ&pg=PA2661 |url-status=live }}</ref><ref name="JamesonGroot2015" /><ref name="ReiterMauras2010">{{cite journal | vauthors = Reiter EO, Mauras N, McCormick K, Kulshreshtha B, Amrhein J, De Luca F, O'Brien S, Armstrong J, Melezinkova H | title = Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT) | journal = Journal of Pediatric Endocrinology & Metabolism | volume = 23 | issue = 10 | pages = 999–1009 | date = October 2010 | pmid = 21158211 | doi = 10.1515/jpem.2010.161 | s2cid = 110630 }}</ref>
* [[Priapism|Overly long-lasting erection]]s in men at 50&nbsp;mg per week to 50&nbsp;mg every other day<ref name="LeveyKutlu2011">{{cite journal | vauthors = Levey HR, Kutlu O, Bivalacqua TJ | title = Medical management of ischemic stuttering priapism: a contemporary review of the literature | journal = Asian Journal of Andrology | volume = 14 | issue = 1 | pages = 156–163 | date = January 2012 | pmid = 22057380 | pmc = 3753435 | doi = 10.1038/aja.2011.114 }}</ref><ref name="BroderickKadioglu2010">{{cite journal | vauthors = Broderick GA, Kadioglu A, Bivalacqua TJ, Ghanem H, Nehra A, Shamloul R | title = Priapism: pathogenesis, epidemiology, and management | journal = The Journal of Sexual Medicine | volume = 7 | issue = 1 Pt 2 | pages = 476–500 | date = January 2010 | pmid = 20092449 | doi = 10.1111/j.1743-6109.2009.01625.x }}</ref><ref name="ChowPayne2008">{{cite journal | vauthors = Chow K, Payne S | title = The pharmacological management of intermittent priapismic states | journal = BJU International | volume = 102 | issue = 11 | pages = 1515–1521 | date = December 2008 | pmid = 18793304 | doi = 10.1111/j.1464-410X.2008.07951.x | s2cid = 35399393 | doi-access = free }}</ref><ref name="DahmRao2002">{{cite journal | vauthors = Dahm P, Rao DS, Donatucci CF | title = Antiandrogens in the treatment of priapism | journal = Urology | volume = 59 | issue = 1 | pages = 138 | date = January 2002 | pmid = 11796309 | doi = 10.1016/S0090-4295(01)01492-3 }}</ref><ref name="Dart2004" /><ref name="Skidmore-Roth2013" /><ref name="YuanDeSouza2008" />

The medication has been suggested for but has uncertain effectiveness in the following indication:

* [[Hypersexuality]] and [[paraphilia]]s, particularly in combination with [[chemical castration]]<ref name="pmid21956411">{{cite journal |vauthors=Gooren LJ |title=Clinical review: Ethical and medical considerations of androgen deprivation treatment of sex offenders |journal=The Journal of Clinical Endocrinology & Metabolism |volume=96 |issue=12 |pages=3628–37 |year=2011 |pmid=21956411 |doi=10.1210/jc.2011-1540 |doi-access=free }}</ref><ref name="pmid19297634">{{cite journal |vauthors=Giltay EJ, Gooren LJ |title=Potential side effects of androgen deprivation treatment in sex offenders |journal=The Journal of the American Academy of Psychiatry and the Law |volume=37 |issue=1 |pages=53–8 |year=2009 |pmid=19297634 }}</ref><ref name="pmid27032060">{{cite journal |vauthors=Khan O, Mashru A |title=The efficacy, safety and ethics of the use of testosterone-suppressing agents in the management of sex offending |journal=Current Opinion in Endocrinology, Diabetes and Obesity |volume=23 |issue=3 |pages=271–8 |year=2016 |pmid=27032060 |doi=10.1097/MED.0000000000000257 |s2cid=43286710 }}</ref><ref name="APA1999">{{cite book |title=Dangerous Sex Offenders: A Task Force Report of the American Psychiatric Association |url=https://books.google.com/books?id=PbC8kWQ-n1sC&pg=PA111 |year=1999 |publisher=American Psychiatric Pub |isbn=978-0-89042-280-9 |pages=111–}}</ref><ref name="pmid22005210">{{cite journal |vauthors=Houts FW, Taller I, Tucker DE, Berlin FS |title=Androgen deprivation treatment of sexual behavior |journal=Advances in Psychosomatic Medicine |volume=31 |pages=149–63 |year=2011 |pmid=22005210 |doi=10.1159/000330196 |isbn=978-3-8055-9825-5 }}</ref><ref name="pmid2189544">{{cite journal |vauthors=Rousseau L, Couture M, Dupont A, Labrie F, Couture N |title=Effect of combined androgen blockade with an LHRH agonist and flutamide in one severe case of male exhibitionism |journal=The Canadian Journal of Psychiatry |volume=35 |issue=4 |pages=338–41 |year=1990 |pmid=2189544 |doi=10.1177/070674379003500412 |s2cid=28970865 }}</ref>

For more information on these uses, see the [[medical uses of bicalutamide]] article.

===Available forms===
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Bicalutamide is available for the treatment of prostate cancer in most developed countries,<ref name="IndexNominum2000">{{cite book |editor=Swiss Pharmaceutical Society |title=Index Nominum 2000: International Drug Directory |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA123 |date=January 2000 |publisher=Taylor & Francis |isbn=978-3-88763-075-1 |pages=123–|url-status=live |archive-url=https://web.archive.org/web/20160424054101/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA123 |archive-date=24 April 2016 |df=dmy-all}}</ref><ref name="Drugs.com-2"/><ref name="Martindale2011">{{cite book |vauthors=Sweetman SC |title=Martindale: The Complete Drug Reference |url=https://books.google.com/books?id=r_qfcQAACAAJ |year=2011 |publisher=Pharmaceutical Press |isbn=978-0-85369-933-0 |pages=750–751 |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143130/https://books.google.com/books?id=r_qfcQAACAAJ |url-status=live }}</ref> including over 80&nbsp;countries worldwide.<ref name=Ak1999/><ref name="AstraZeneca1999"/> It is available in 50&nbsp;mg, 80&nbsp;mg (in Japan),<ref name="SuzukiKamiya2008">{{cite journal |vauthors=Suzuki H, Kamiya N, Imamoto T, Kawamura K, Yano M, Takano M, Utsumi T, Naya Y, Ichikawa T |title=Current topics and perspectives relating to hormone therapy for prostate cancer |journal=International Journal of Clinical Oncology |volume=13 |issue=5 |pages=401–10 |date=October 2008 |pmid=18946750 |doi=10.1007/s10147-008-0830-y|s2cid=32859879 }}</ref> and 150&nbsp;mg tablets for [[oral administration]].<ref name="WhiteBradnam2015">{{cite book |vauthors=White R, Bradnam V |title=Handbook of Drug Administration via Enteral Feeding Tubes |edition=3rd |url=https://books.google.com/books?id=yyikBwAAQBAJ&pg=PA133 |date=11 March 2015 |publisher=Pharmaceutical Press |isbn=978-0-85711-162-3 |pages=133– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143141/https://books.google.com/books?id=yyikBwAAQBAJ&pg=PA133 |url-status=live }}</ref><ref name="MortonHall2001">{{cite book | vauthors = Morton IK, Hall J |title=The Avery Complete Guide to Medicines |url=https://books.google.com/books?id=0MlN61X5ogkC&q=bicalutamide |year=2001 |publisher=Avery |isbn=978-1-58333-105-7 |pages=105–106}}</ref> The drug is registered for use as a 150&nbsp;mg/day monotherapy for the treatment of {{abbr|LAPC|locally advanced prostate cancer}} in at least 55 countries,<ref name="Cockshott2004" /> with the {{abbr|U.S.|United States}} being a notable exception where it is registered only for use at a dosage of 50&nbsp;mg/day in combination with castration.<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=679–680 |quote=From a structural standpoint, antiandrogens are classified as steroidal, including cyproterone [acetate] (Androcur) and megestrol [acetate], or nonsteroidal, including flutamide (Eulexin, others), bicalutamide (Casodex), and nilutamide (Nilandron). The steroidal antiandrogens are rarely used. |access-date=27 September 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> No other [[pharmaceutical formulation|formulations]] or [[routes of administration]] are available or used.<ref name="WhiteBradnam2015" /> All formulations of bicalutamide are specifically indicated for the treatment of prostate cancer alone or in combination with surgical or medication castration.<ref name="LemkeWilliams2008" /> Due to the low [[water solubility]] of bicalutamide, bicalutamide in oral bicalutamide tablets is [[micronization|micronized]] to ensure small and consistent [[particle size]]s and optimize oral [[bioavailability]].<ref name="pmid12496872">{{cite journal | vauthors = Kolvenbag GJ, Furr BJ, Blackledge GR | title = Receptor affinity and potency of non-steroidal antiandrogens: translation of preclinical findings into clinical activity | journal = Prostate Cancer Prostatic Dis | volume = 1 | issue = 6 | pages = 307–314 | date = December 1998 | pmid = 12496872 | doi = 10.1038/sj.pcan.4500262 | s2cid = 33497597 | url = | quote = In addition, since bicalutamide has a low solubility, authentic Casodex® is micronised to ensure a small and consistent particle size to optimise bioavailability.}}</ref><ref name="Cockshott2004" />

A [[combination drug|combined formulation]] of bicalutamide and the [[GnRH agonist|{{abbr|GnRH|gonadotropin-releasing hormone}} agonist]] [[goserelin]] in which goserelin is provided as a [[subcutaneous tissue|subcutaneous]] [[implant (medicine)|implant]] for [[injection (medicine)|injection]] and bicalutamide is included as 50&nbsp;mg tablets for oral ingestion is marketed in Australia and [[New Zealand]] under the brand name ZolaCos CP (Zoladex–Cosudex Combination Pack).<ref name="Martindale2011" /><ref name="Drugs.com-3">{{cite web |title=Zolacos CP |url=https://www.drugs.com/international/zolacos-cp.html |work=Drugs.com |url-status=live |archive-url=https://web.archive.org/web/20160920130215/https://www.drugs.com/international/zolacos-cp.html |archive-date=20 September 2016 |df=dmy-all}}</ref><ref name="ZolacosCPLabelAu">{{cite web |title=Zolacos CP | archive-url = https://web.archive.org/web/20160917215734/https://www.betterhealth.vic.gov.au/~/media/bhc/files/medicine%20guides%20library/07/cmi7435.pdf |url=https://www.betterhealth.vic.gov.au/~/media/bhc/files/medicine%20guides%20library/07/cmi7435.pdf |archive-date=17 September 2016 | url-status = dead |publisher=MIMS/myDr |date=April 2007}}</ref><ref name="ZolacosCPLabelNZ">{{cite web |url=http://www.medsafe.govt.nz/profs/datasheet/z/ZolaCosCP.pdf |title=ZOLACOS CP |work=New Zealand Data Sheet |date=25 July 2016 |url-status=live |archive-url=https://web.archive.org/web/20160919034509/http://www.medsafe.govt.nz/profs/datasheet/z/ZolaCosCP.pdf |archive-date=19 September 2016 |df=dmy-all}}</ref>

==Contraindications==
Bicalutamide is [[Pregnancy category#United States|pregnancy category X]], or "contraindicated in pregnancy", in the {{abbr|U.S.|United States}},<ref name="FDALabel" /> and [[Pregnancy category#Australia|pregnancy category D]], the second most restricted rating, in Australia.<ref name="TGALabel" /> As such, it is contraindicated in women during pregnancy, and women who are sexually active and who can or may become pregnant are strongly recommended to take bicalutamide only in combination with adequate [[contraception]].<ref name="IswaranImai1997" /><ref name="Smith2013" /> It is unknown whether bicalutamide is excreted in [[breast milk]], but many drugs are excreted in breast milk, and for this reason, bicalutamide treatment is similarly not recommended while [[breastfeeding]].<ref name="Dart2004" /><ref name="FDALabel" />

In individuals with severe, though not mild-to-moderate [[hepatic impairment]], there is evidence that the elimination of bicalutamide is slowed, and hence, caution may be warranted in these patients as circulating levels of bicalutamide may be increased.<ref name="Cockshott2004" /><ref name="SkeelKhleif2011">{{cite book | vauthors = Skeel RT, Khleif SN |title=Handbook of Cancer Chemotherapy |url=https://books.google.com/books?id=6Nz_87OLrtcC&pg=PA724 |year=2011 |publisher=Lippincott Williams & Wilkins |pages=724–|url-status=live |archive-url=https://web.archive.org/web/20160529144852/https://books.google.com/books?id=6Nz_87OLrtcC&pg=PA724 |archive-date=29 May 2016 |df=dmy-all|isbn=9781608317820 }}</ref> In severe hepatic impairment, the elimination half-life of the active (''R'')-[[enantiomer]] of bicalutamide is increased by about 1.75-fold (76% increase; elimination half-life of 5.9 and 10.4&nbsp;days for normal and impaired patients, respectively).<ref name="Wellington2006" /><ref>{{cite book |title=Mosby's GenRx: A Comprehensive Reference for Generic and Brand Prescription Drugs |url=https://books.google.com/books?id=QxsobYYgm8oC |year=2001 |publisher=Mosby |isbn=978-0-323-00629-3 |pages=289–290}}</ref><ref name="PDR2004">{{cite book |vauthors=Duplay D |title=Physicians' Desk Reference |url=https://books.google.com/books?id=_sf2G6ZPDKAC |year=2004 |publisher=Thomson PDR |isbn=978-1-56363-471-0 |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143131/https://books.google.com/books?id=_sf2G6ZPDKAC |url-status=live }}</ref> The elimination half-life of bicalutamide is unchanged in [[renal impairment]].<ref name="ChabnerLongo2010" />

==Side effects==
{{Main|Side effects of bicalutamide}}
{{Major side effects of bicalutamide alone}}

The [[side effect]] profile of bicalutamide is highly dependent on sex; that is, on whether the person is male or female. In men, due to [[hypoandrogenism|androgen deprivation]], a variety of side effects of varying severity may occur during bicalutamide treatment, with [[mastodynia|breast pain/tenderness]] and [[gynecomastia]] ([[breast development]]/[[mammoplasia|enlargement]]) being the most common.<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=27 September 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><ref name="WirthHakenberg2007">{{cite journal |vauthors=Wirth MP, Hakenberg OW, Froehner M |title=Antiandrogens in the treatment of prostate cancer |journal=European Urology |volume=51 |issue=2 |pages=306–13; discussion 314 |date=February 2007 |pmid=17007995 |doi=10.1016/j.eururo.2006.08.043}}</ref> Gynecomastia occurs in up to 80% of men treated with bicalutamide monotherapy, and is of mild-to-moderate severity in more than 90% of affected men.<ref name="WirthHakenberg2007" /><ref name="WellingtonKeam2006">{{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=837–50 |year=2006 |pmid=16706554 |doi=10.2165/00003495-200666060-00007|s2cid=46966712 }}</ref> In addition to breast changes, physical [[feminization (biology)|feminization]] and [[demasculinization]] in general, including reduced [[body hair]] growth, decreased [[muscle mass]] and [[muscle strength|strength]], [[gynoid fat distribution|feminine]] changes in [[body fat percentage|fat mass]] and [[fat distribution|distribution]], reduced [[human penis size|penile length]], and decreased [[Ejaculation#Volume|semen/ejaculate volume]], may occur in men.<ref name="Lehne2013" /><ref name="Higano2003">{{cite journal |vauthors=Higano CS |title=Side effects of androgen deprivation therapy: monitoring and minimizing toxicity |journal=Urology |volume=61 |issue=2 Suppl 1 |pages=32–8 |date=February 2003 |pmid=12667885 |doi=10.1016/S0090-4295(02)02397-X}}</ref><ref name="pmid20626600" /><ref name="pmid23008326">{{cite journal |vauthors=Higano CS |title=Sexuality and intimacy after definitive treatment and subsequent androgen deprivation therapy for prostate cancer |journal=Journal of Clinical Oncology |volume=30 |issue=30 |pages=3720–5 |year=2012 |pmid=23008326 |doi=10.1200/JCO.2012.41.8509 }}</ref> Other side effects that have been observed in men and that are similarly related to androgen deprivation include [[hot flash]]es, [[sexual dysfunction]] (e.g., loss of [[libido]], [[erectile dysfunction]]), [[depression (mood)|depression]], [[fatigue (medical)|fatigue]], [[weakness]], and [[anemia]].<ref name="Lehne2013" /><ref name="Kolvenbag1996">{{cite journal |vauthors=Kolvenbag GJ, Blackledge GR |title=Worldwide activity and safety of bicalutamide: a summary review |journal=Urology |volume=47 |issue=1A Suppl |pages=70–9; discussion 80–4 |date=January 1996 |pmid=8560681 |doi= 10.1016/s0090-4295(96)80012-4|quote=Bicalutamide is a new antiandrogen that offers the convenience of once-daily administration, demonstrated activity in prostate cancer, and an excellent safety profile. Because it is effective and offers better tolerability than flutamide, bicalutamide represents a valid first choice for antiandrogen therapy in combination with castration for the treatment of patients with advanced prostate cancer.}}</ref><ref name="ResnickThompson2000">{{cite book | vauthors = Resnick MI, Thompson IM |title=Advanced Therapy of Prostate Disease |url=https://books.google.com/books?id=9AKuf7rzfjcC&pg=PA379 |year=2000 |publisher=PMPH-USA |isbn=978-1-55009-102-1 |pages=379–|url-status=live |archive-url=https://web.archive.org/web/20160610095331/https://books.google.com/books?id=9AKuf7rzfjcC&pg=PA379 |archive-date=10 June 2016 |df=dmy-all}}</ref> However, most men have preserved sexual function with bicalutamide monotherapy.<ref name="IversenMelezinek2001" /><ref name="pmid12603397a" /> In females, due to the minimal biological importance of androgens in this sex,<ref name="pmid28343552">{{cite journal |vauthors=Kathryn Korkidakis A, Reid RL |title=Testosterone in Women: Measurement and Therapeutic Use |journal=Journal of Obstetrics and Gynaecology Canada |volume=39 |issue=3 |pages=124–130 |year=2017 |pmid=28343552 |doi=10.1016/j.jogc.2017.01.006 }}</ref><ref name="pmid26358173">{{cite journal |vauthors=Davis SR, Wahlin-Jacobsen S |title=Testosterone in women--the clinical significance |journal=The Lancet Diabetes & Endocrinology |volume=3 |issue=12 |pages=980–92 |year=2015 |pmid=26358173 |doi=10.1016/S2213-8587(15)00284-3 }}</ref> the side effects of pure antiandrogens or {{abbr|NSAAs|nonsteroidal antiandrogens}} are few, and bicalutamide has been found to be very well tolerated.<ref name="Shapiro2012" /> However, bicalutamide has been found to increase levels of [[total cholesterol|total]] and [[LDL cholesterol]] in women.<ref name="pmid33334002">{{cite journal | vauthors = Cignarella A, Mioni R, Sabbadin C, Dassie F, Parolin M, Vettor R, Barbot M, Scaroni C | title = Pharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS | journal = Int J Mol Sci | volume = 21 | issue = 24 | date = December 2020 | page = 9554 | pmid = 33334002 | pmc = 7765466 | doi = 10.3390/ijms21249554 | url = | doi-access = free }}</ref><ref name="pmid33070640">{{cite journal | vauthors = Luque-Ramírez M, Ortiz-Flores AE, Nattero-Chávez L, Escobar-Morreale HF | title = A safety evaluation of current medications for adult women with the polycystic ovarian syndrome not pursuing pregnancy | journal = Expert Opin Drug Saf | volume = 19 | issue = 12 | pages = 1559–1576 | date = December 2020 | pmid = 33070640 | doi = 10.1080/14740338.2020.1839409 | s2cid = 224784192 | url = }}</ref><ref name="pmid29211888" /> The non-pharmacological side-effect profile of bicalutamide (i.e., side effects not related to its antiandrogenic activity) is said to be similar to that with [[placebo]].<ref name="FourcadeMcLeod2004">{{cite journal | vauthors = Fourcade RO, McLeod D | title = Tolerability of Antiandrogens in the Treatment of Prostate Cancer | journal = UroOncology | date = March 2004 | volume = 4 | issue = 1 | pages = 5–13 | issn = 1561-0950 | doi = 10.1080/1561095042000191655 | pmid = | url = | quote = Based on the available evidence, bicalutamide appears to have a better profile of non-pharmacological side effects than either flutamide or nilutamide; no specific nonpharmacological complications have yet been linked to this agent, while the incidence of the side effects such as diarrhoea and abnormal liver function appears to be lower than for the other two non-steroidal compounds. Furthermore, the recent data from the EPC programme suggest that the non-pharmacological side-effect profile of bicalutamide is not dissimilar to that of placebo (Table m [3].}}</ref> In any case, general side effects of bicalutamide that might occur in either sex include [[diarrhea]], [[constipation]], [[abdominal pain]], [[nausea]], [[dry skin]], [[pruritus|itching]], and [[rash]].<ref name="Kolvenbag1996" /><ref name="Dart2004" /><ref name="pmid7579554">{{cite journal |vauthors=Lunglmayr G |title=Efficacy and tolerability of Casodex in patients with advanced prostate cancer. International Casodex Study Group |journal=Anti-Cancer Drugs |volume=6 |issue=4 |pages=508–13 |date=August 1995 |pmid=7579554 |doi=10.1097/00001813-199508000-00003}}</ref><ref name="pmid10388026">{{cite journal | vauthors = McLeod DG | title = Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer | journal = Oncologist | volume = 2 | issue = 1 | pages = 18–27 | date = 1997 | pmid = 10388026 | doi = 10.1634/theoncologist.2-1-18| doi-access = free }}</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–|url-status=live |archive-url=https://web.archive.org/web/20160507051525/https://books.google.com/books?id=mpZ8Dp2KdHMC&pg=PA479 |archive-date=7 May 2016 |df=dmy-all}}</ref><ref name="JamnickyNam2012">{{cite book |vauthors=Jamnicky L, Nam R |title=Canadian Guide to Prostate Cancer |url=https://books.google.com/books?id=EFJhvLJeWX4C&pg=PT177 |date=5 November 2012 |publisher=John Wiley & Sons |isbn=978-1-118-51565-5 |pages=177– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143131/https://books.google.com/books?id=EFJhvLJeWX4C&pg=PT177 |url-status=live }}</ref> The drug is well-tolerated at higher dosages than 50&nbsp;mg/day, up to 600{{nbsp}}mg/day, with rare additional side effects.<ref name="ChabnerLongo2010" /><ref name="pmid9471040">{{cite journal | vauthors = Tyrrell CJ, Denis L, Newling D, Soloway M, Channer K, Cockshott ID | title = Casodex 10-200 mg daily, used as monotherapy for the treatment of patients with advanced prostate cancer. An overview of the efficacy, tolerability and pharmacokinetics from three phase II dose-ranging studies. Casodex Study Group | journal = Eur. Urol. | volume = 33 | issue = 1 | pages = 39–53 | year = 1998 | pmid = 9471040 | doi = 10.1159/000019526 | s2cid = 71758492 | url = https://www.karger.com/Article/Pdf/19526 | access-date = 13 April 2023 | archive-date = 1 February 2022 | archive-url = https://web.archive.org/web/20220201084113/https://www.karger.com/Article/Pdf/19526 | url-status = live | url-access = subscription }}</ref><ref name="TyrrellIversen2006">{{cite journal |vauthors=Tyrrell CJ, Iversen P, Tammela T, Anderson J, Björk T, Kaisary AV, Morris T |title=Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration |journal=BJU International |volume=98 |issue=3 |pages=563–72 |date=September 2006 |pmid=16771791 |doi=10.1111/j.1464-410X.2006.06275.x|s2cid=41672303}}</ref>

Bicalutamide has been associated with abnormal [[liver function tests]] such as [[elevated liver enzymes]].<ref name="Kolvenbag1996" /><ref name="Wellington2006" /> In the [[Early Prostate Cancer (clinical programme)|Early Prostate Cancer]] (EPC) clinical programme of bicalutamide for {{Abbr|LPC|localized prostate cancer}} and {{Abbr|LAPC|locally advanced prostate cancer}}, the rate of abnormal liver function tests with bicalutamide monotherapy was 3.4% relative to 1.9% for [[placebo]].<ref name="Wellington2006" /><ref name="SeeWirth2002">{{cite journal |vauthors=See WA, Wirth MP, McLeod DG, Iversen P, Klimberg I, Gleason D, Chodak G, Montie J, Tyrrell C, Wallace DM, Delaere KP, Vaage S, Tammela TL, Lukkarinen O, Persson BE, Carroll K, Kolvenbag GJ |title=Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program |journal=The Journal of Urology |volume=168 |issue=2 |pages=429–35 |date=August 2002 |pmid=12131282 |doi=10.1016/S0022-5347(05)64652-6}}</ref> However, higher rates, up to 11%, have been seen in other studies.<ref name="pmid35032336" /><ref name="FDALabel" /> [[Liver|Hepatic]] changes that have necessitated discontinuation of bicalutamide, such as marked increases in liver enzymes or [[hepatitis]], have occurred in 0.3 to 1.5% of men in clinical trials, or approximately 1% overall.<ref name="FDALabel" /><ref name="Wellington2006" /><ref name="MahlerVerhelst1998" /><ref name="SeeWirth2002" /><ref name="pmid8560679">{{cite journal | vauthors = Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G | title = Maximal androgen blockade for patients with metastatic prostate cancer: outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy. Casodex Combination Study Group | journal = Urology | volume = 47 | issue = 1A Suppl | pages = 54–60; discussion 80–4 | date = January 1996 | pmid = 8560679 | doi = 10.1016/s0090-4295(96)80010-0 | url = }}</ref> Elevated liver enzymes with bicalutamide usually occur within the first 3 to 6&nbsp;months of treatment.<ref name="Kolvenbag1996" /><ref name="FDALabel" /> Monitoring of liver function during treatment is recommended, particularly in the first few months.<ref name="Wellington2006" /><ref name="Lehne2013" /> In men with early prostate cancer, bicalutamide monotherapy has been found to increase non-prostate cancer [[mortality rate|mortality]].<ref name="pmid35569476">{{cite journal | vauthors = Jia AY, Spratt DE | title = Bicalutamide Monotherapy With Radiation Therapy for Localized Prostate Cancer: A Non-Evidence-Based Alternative | journal = Int J Radiat Oncol Biol Phys | volume = 113 | issue = 2 | pages = 316–319 | date = June 2022 | pmid = 35569476 | doi = 10.1016/j.ijrobp.2022.01.037 | s2cid = 248765294 | url = | quote = Four other randomized trials using BICmono have also raised concerns about either lack of efficacy or even harm from this treatment approach compared with placebo or no hormone therapy. SPCG-6 randomized 1218 patients to either 150 mg of BICmono daily or placebo. In the subset of patients with LPCa managed with observation, survival was significantly worse with BIC than placebo (hazard ratio [HR], 1.47; 95% confidence interval, 1.06-2.03).10 Two other randomized trials were part of the early prostate cancer program,11 which conducted 3 randomized trials that were pooled together to determine the benefit of BICmono (SPCG-6 was one of the 3 trials). Overall, in the combined 8113 patient pooled cohort, after a median follow-up of 7 years, there was no improvement even in progression-free survival from the use of adjuvant BIC in LPCa, and there was a trend for worse overall survival (HR, 1.16; 95% confidence interval, 0.99-1.37; P = .07). [...] Although not in LPCa, NRG/RTOG 9601 demonstrated findings consistent with the prior trials.12 This trial randomized men to postprostatectomy salvage radiation therapy plus placebo versus 150 mg of BICmono daily for 2 years. After a median follow-up of 13 years, the trial showed that there were significantly more grade 3 to 5 cardiac events in the BICmono arm. In patients with less aggressive disease with lower PSAs (prostate-specific antigens; more analogous to LPCa), other-cause mortality was significantly higher in the BICmono arm. In patients with high PSAs >1.5 ng/mL (which with modern molecular positron emission tomography imaging would be expected to have high rates of regional and distant metastatic disease), a survival benefit from the addition of BIC was observed. This is consistent with results from the early prostate cancer studies that showed that only patients with more advanced disease derived benefit from BICmono.10 Thus, all the randomized evidence from 5 trials (Table 1) demonstrates that, in LPCa, BICmono had no clinically significant oncologic activity over placebo/no treatment, and consistent trends with long-term use resulted in worse survival.}}</ref><ref name="IversenJohansson2004">{{cite journal |vauthors=Iversen P, Johansson JE, Lodding P, Lukkarinen O, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Carroll K |title=Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6 |journal=The Journal of Urology |volume=172 |issue=5 Pt 1 |pages=1871–6 |date=November 2004 |pmid=15540741 |doi=10.1097/01.ju.0000139719.99825.54}}</ref><ref name="Wellington2006" /> The reasons for the increase in mortality with bicalutamide in these men are unknown, but possible factors could include androgen deprivation or drug-related toxicity of bicalutamide.<ref name="pmid16706554">{{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 = 837–50 | date = 2006 | pmid = 16706554 | doi = 10.2165/00003495-200666060-00007 | s2cid = 46966712 | url = }}</ref><ref name="pmid17130095">{{cite journal |vauthors=Iversen P, Johansson JE, Lodding P, Kylmälä T, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Armstrong J |title=Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years |journal=Scandinavian Journal of Urology and Nephrology |volume=40 |issue=6 |pages=441–52 |year=2006 |pmid=17130095 |doi=10.1080/00365590601017329 |s2cid=25862814 }}</ref>

There are 10 published [[case report]]s of [[hepatotoxicity|liver toxicity]] associated with bicalutamide as of 2022.<ref name="pmid35332669">{{cite journal | vauthors = Trüeb RM, Luu NC, Uribe NC, Régnier A | title = Comment on: Bicalutamide and the new perspectives for female pattern hair loss treatment: What dermatologists should know | journal = J Cosmet Dermatol | volume = 21 | issue = 12 | pages = 7200–7201 | date = December 2022 | pmid = 35332669 | doi = 10.1111/jocd.14936 | s2cid = 247677549 | url = | quote = Indeed, due to the minimal biological importance of androgens in women, the adverse effects of bicalutamide are few. And yet, bicalutamide has been associated with elevated liver enzymes, and as of 2021, there have been 10 case reports of liver toxicity associated with bicalutamide, with fatality occurring in 2 cases.2}}</ref><ref name="GretarsdottirBjornsdottir2018">{{cite journal | vauthors = Gretarsdottir HM, Bjornsdottir E, Bjornsson ES | title = Bicalutamide-Associated Acute Liver Injury and Migratory Arthralgia: A Rare but Clinically Important Adverse Effect | journal = Case Reports in Gastroenterology | volume = 12 | issue = 2 | year = 2018 | pages = 266–70 | issn = 1662-0631 | doi = 10.1159/000485175| doi-access = free | hdl = 20.500.11815/1492 | hdl-access = free }}</ref><ref name="pmid24967002">{{cite journal | vauthors = Hussain S, Haidar A, Bloom RE, Zayouna N, Piper MH, Jafri SM | title = Bicalutamide-induced hepatotoxicity: A rare adverse effect | journal = Am J Case Rep | volume = 15 | pages = 266–70 | date = 2014 | pmid = 24967002 | pmc = 4068966 | doi = 10.12659/AJCR.890679 }}</ref><ref name="pmid27099451">{{cite journal | vauthors = Yun GY, Kim SH, Kim SW, Joo JS, Kim JS, Lee ES, Lee BS, Kang SH, Moon HS, Sung JK, Lee HY, Kim KH | title = Atypical onset of bicalutamide-induced liver injury | journal = World J. Gastroenterol. | volume = 22 | issue = 15 | pages = 4062–5 | date = April 2016 | pmid = 27099451 | pmc = 4823258 | doi = 10.3748/wjg.v22.i15.4062 | doi-access = free }}</ref> Death occurred in 2 of these cases.<ref name="pmid35332669" /><ref name="pmid18657023">{{cite journal | vauthors = O'Bryant CL, Flaig TW, Utz KJ | title = Bicalutamide-associated fulminant hepatotoxicity | journal = Pharmacotherapy | volume = 28 | issue = 8 | pages = 1071–5 | year = 2008 | pmid = 18657023 | doi = 10.1592/phco.28.8.1071 | s2cid = 20315801 }}</ref><ref name="pmid18796378">{{cite journal | vauthors = Castro Beza I, Sánchez Ruiz J, Peracaula Espino FJ, Villanego Beltrán MI | title = Drug-related hepatotoxicity and hepatic failure following combined androgen blockade | journal = Clin Transl Oncol | volume = 10 | issue = 9 | pages = 591–2 | date = September 2008 | pmid = 18796378 | doi = 10.1007/s12094-008-0256-5 }}</ref> Hundreds of additional cases of liver complications in people taking bicalutamide exist in the [[FDA Adverse Event Reporting System]] (FAERS) database.<ref name="FAERS">{{cite journal | url=https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard | title=FDA Adverse Event Reporting System (FAERS) Public Dashboard | journal=FDA | date=22 October 2021 | access-date=15 February 2023 | archive-date=15 February 2023 | archive-url=https://web.archive.org/web/20230215182941/https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard | url-status=dead }}</ref> In all of the published case reports of liver toxicity with bicalutamide, the onset of symptoms was within the first 6&nbsp;months of treatment.<ref name="GretarsdottirBjornsdottir2018" /><ref name="pmid24967002" /><ref name="pmid27099451" /> Symptoms that may indicate [[liver disease|liver dysfunction]] include nausea, vomiting, abdominal pain, fatigue, [[anorexia (symptom)|anorexia]], [[influenza-like illness|"flu-like" symptoms]], [[choluria|dark urine]], and [[jaundice]].<ref name="FDALabel" /> There are also published case reports of [[interstitial pneumonitis]] and [[eosinophilic lung disease]] associated with bicalutamide.<ref name="Dart2004b">{{cite book | vauthors = Dart RC |title=Medical Toxicology |url=https://books.google.com/books?id=BfdighlyGiwC&pg=PA497 |year=2004 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2845-4 |pages=497–|url-status=live |archive-url=https://web.archive.org/web/20160511213240/https://books.google.com/books?id=BfdighlyGiwC&pg=PA497 |archive-date=11 May 2016 |df=dmy-all}}</ref><ref name="MasagoWatanabe2011">{{cite journal |vauthors=Masago T, Watanabe T, Nemoto R, Motoda K |title=Interstitial pneumonitis induced by bicalutamide given for prostate cancer |journal=International Journal of Clinical Oncology |volume=16 |issue=6 |pages=763–5 |date=December 2011 |pmid=21537882 |doi=10.1007/s10147-011-0239-x|s2cid=24068787 }}</ref><ref name="Aronson2014">{{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=jTc3AAAAQBAJ&pg=PA740 |date=4 March 2014 |publisher=Newnes |isbn=978-0-444-62636-3 |pages=740–|url-status=live |archive-url=https://web.archive.org/web/20160506202559/https://books.google.com/books?id=jTc3AAAAQBAJ&pg=PA740 |archive-date=6 May 2016 |df=dmy-all}}</ref> along with hundreds of additional instances in the FAERS database as well.<ref name="FAERS" /> Interstitial pneumonitis can potentially progress to [[pulmonary fibrosis]] and may be fatal. Symptoms that may indicate [[respiratory disease|lung dysfunction]] include [[dyspnea]] (difficult breathing or shortness of breath), cough, and [[pharyngitis]] ([[inflammation]] of the [[pharynx]], resulting in [[sore throat]]).<ref name="pmid15195196">{{cite journal |vauthors=Daba MH, El-Tahir KE, Al-Arifi MN, Gubara OA |title=Drug-induced pulmonary fibrosis |journal=Saudi Medical Journal |volume=25 |issue=6 |pages=700–6 |date=June 2004 |pmid=15195196 }}</ref> The exact incidence of liver toxicity and interstitial pneumonitis with bicalutamide are unknown, but both are said to be very rare events.<ref name="pmid24967002" /><ref name="TholeManso2004">{{cite journal |vauthors=Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A |title=Hepatotoxicity induced by antiandrogens: a review of the literature |journal=Urologia Internationalis |volume=73 |issue=4 |pages=289–95 |year=2004 |pmid=15604569 |doi=10.1159/000081585|s2cid=24799765 }}</ref><ref name="RicciBuzzatti2014">{{cite journal |vauthors=Ricci F, Buzzatti G, Rubagotti A, Boccardo F |title=Safety of antiandrogen therapy for treating prostate cancer |journal=Expert Opinion on Drug Safety |volume=13 |issue=11 |pages=1483–99 |date=November 2014 |pmid=25270521 |doi=10.1517/14740338.2014.966686|s2cid=207488100 }}</ref> A few cases of [[photosensitivity]] have been reported with bicalutamide.<ref name="LeeOda2016" /> [[Hypersensitivity reaction]]s ([[drug allergy]]) like [[angioedema]] and [[urticaria|hives]] have also uncommonly been reported in association with bicalutamide.<ref name="FDALabel" />

Because it is an antiandrogen, bicalutamide has a theoretical risk of [[birth defect]]s like [[ambiguous genitalia]] in male [[fetus]]es.<ref name="IswaranImai1997">{{cite journal |vauthors=Iswaran TJ, Imai M, Betton GR, Siddall RA |title=An overview of animal toxicology studies with bicalutamide (ICI 176,334) |journal=The Journal of Toxicological Sciences |volume=22 |issue=2 |pages=75–88 |date=May 1997 |pmid=9198005 |doi=10.2131/jts.22.2_75|doi-access=free }}</ref><ref name="Smith2013">{{cite book | vauthors = Smith RE |title=Medicinal Chemistry – Fusion of Traditional and Western Medicine |url=https://books.google.com/books?id=RkDcAwAAQBAJ&pg=PA306 |date=4 April 2013 |publisher=Bentham Science Publishers |isbn=978-1-60805-149-6 |pages=306–|url-status=live |archive-url=https://web.archive.org/web/20160529034219/https://books.google.com/books?id=RkDcAwAAQBAJ&pg=PA306 |archive-date=29 May 2016 |df=dmy-all}}</ref><ref>{{cite book |title=Sex Differences in the Human Brain, their underpinnings and implications |url=https://books.google.com/books?id=JFpq6hYQRhQC&pg=PA44 |date=3 December 2010 |publisher=Elsevier |isbn=978-0-444-53631-0 |pages=44–45 |url-status=live |archive-url=https://web.archive.org/web/20160526221656/https://books.google.com/books?id=JFpq6hYQRhQC |archive-date=26 May 2016 |df=dmy-all}}</ref><ref name="Paoletti2012">{{cite book |vauthors=Paoletti R |title=Chemistry and Brain Development: Proceedings of the Advanced Study Institute on "Chemistry of Brain Development," held in Milan, Italy, September 9–19, 1970 |url=https://books.google.com/books?id=8YbgBwAAQBAJ&pg=PA218 |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-1-4684-7236-3 |pages=218– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143132/https://books.google.com/books?id=8YbgBwAAQBAJ&pg=PA218 |url-status=live }}</ref> Due to its [[teratogen]]ic capacity, [[contraception]] should be used in women taking bicalutamide who are fertile and sexually active.<ref name="PapadimitriouAnagnostisGoulis2022">{{cite book | title = Polycystic Ovary Syndrome | vauthors = Papadimitriou K, Anagnostis P, Goulis DG | chapter = The challenging role of antiandrogens in the management of polycystic ovary syndrome | date = 2022 | pages = 297–314 | publisher = Elsevier | doi = 10.1016/B978-0-12-823045-9.00013-4 | isbn = 9780128230459 | s2cid = 244697776 | url = }}</ref>

===Comparison===
{{See also|Comparison of bicalutamide with other antiandrogens}}

The side effect profile of bicalutamide in men and women differs from that of other antiandrogens and is considered favorable in comparison.<ref name="RamonDenis2007">{{cite book| vauthors = Ramon J, Denis LJ |title=Prostate Cancer|url=https://books.google.com/books?id=Bg6ZbqhhboUC&pg=PA256|date=5 June 2007|publisher=Springer Science & Business Media|isbn=978-3-540-40901-4|pages=256–}}</ref><ref name="pmid12603397a">{{cite journal | vauthors = Anderson J | title = The role of antiandrogen monotherapy in the treatment of prostate cancer | journal = BJU Int. | volume = 91 | issue = 5 | pages = 455–61 | date = March 2003 | pmid = 12603397 | doi = 10.1046/j.1464-410X.2003.04026.x | s2cid = 8639102| doi-access = free }}</ref><ref name="Moser2008">{{cite book|vauthors=Moser L|title=Controversies in the Treatment of Prostate Cancer|url=https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41|date=1 January 2008|publisher=Karger Medical and Scientific Publishers|isbn=978-3-8055-8524-8|pages=41–|access-date=5 January 2016|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112173054/https://books.google.com/books?id=4J4OCRyHWRYC&pg=PA41|url-status=live}}</ref><ref name="Demos2011">{{cite book|title=Prostate Cancer|url=https://books.google.com/books?id=WJkjgbRJe3EC&pg=PA504|date=20 December 2011|publisher=Demos Medical Publishing|isbn=978-1-935281-91-7|pages=504–505|access-date=21 December 2017|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114143141/https://books.google.com/books?id=WJkjgbRJe3EC&pg=PA504|url-status=live}}</ref> Relative to {{abbr|GnRH|gonadotropin-releasing hormone}} analogues and the [[steroidal antiandrogen]] (SAA) [[cyproterone acetate]] (CPA), bicalutamide monotherapy has a much lower incidence and severity of hot flashes and sexual dysfunction.<ref name="IversenMelezinek2001" /><ref name="pmid12603397a" /><ref name="WellingtonKeam2006" /><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=PA149|date=21 February 2009|publisher=Elsevier|isbn=978-0-08-093292-7|pages=149–150, 253–258|access-date=21 December 2017|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114143135/https://books.google.com/books?id=BWMeSwVwfTkC&pg=PA149|url-status=live}}</ref> In addition, unlike {{abbr|GnRH|gonadotropin-releasing hormone}} analogues and {{abbr|CPA|cyproterone acetate}}, bicalutamide monotherapy is not associated with decreased [[bone mineral density]] or [[osteoporosis]].<ref name="WellingtonKeam2006" /><ref name="pmid12603397a" /> Conversely, bicalutamide monotherapy is associated with much higher rates of breast tenderness, gynecomastia, and feminization in men than {{abbr|GnRH|gonadotropin-releasing hormone}} analogues and {{abbr|CPA|cyproterone acetate}}.<ref name="WellingtonKeam2006" /> However, gynecomastia with bicalutamide is rarely severe and discontinuation rates due to this side effect are fairly low.<ref name="WellingtonKeam2006" /><ref name="pmid12603397a" /> These differences in side effects between bicalutamide monotherapy, {{abbr|GnRH|gonadotropin-releasing hormone}} analogues, and {{abbr|CPA|cyproterone acetate}} are attributed to the fact that whereas {{abbr|GnRH|gonadotropin-releasing hormone}} analogues and {{abbr|CPA|cyproterone acetate}} suppress estrogen production, bicalutamide monotherapy does not lower estrogen levels and in fact actually increases them.<ref name="WellingtonKeam2006" />

Bicalutamide does not share the risk of [[neuropsychiatry|neuropsychiatric]] side effects like [[fatigue (medical)|fatigue]] as well as [[cardiovascular]] side effects like [[coagulation]] changes, [[thrombosis|blood clot]]s, [[water retention (medicine)|fluid retention]], [[ischemic cardiomyopathy]], and adverse [[serum lipids|serum lipid]] changes that {{abbr|CPA|cyproterone acetate}} has been associated with.<ref name="Aronson2009" /><ref name="Barrett2007">{{cite book|vauthors=Barrett J|title=Transsexual and Other Disorders of Gender Identity: A Practical Guide to Management|url=https://books.google.com/books?id=I-8qZlGIpnQC&pg=PA174|year=2007|publisher=Radcliffe Publishing|isbn=978-1-85775-719-4|pages=174–|access-date=27 September 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114143135/https://books.google.com/books?id=I-8qZlGIpnQC&pg=PA174|url-status=live}}</ref><ref name="pmid12190640">{{cite journal | vauthors = Rushton DH | title = Nutritional factors and hair loss | journal = Clin. Exp. Dermatol. | volume = 27 | issue = 5 | pages = 396–404 | year = 2002 | pmid = 12190640 | doi = 10.1046/j.1365-2230.2002.01076.x| s2cid = 39327815 }}</ref><ref name="pmid10936469">{{cite journal | vauthors = Boccardo F | title = Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy? | journal = Crit. Rev. Oncol. Hematol. | volume = 35 | issue = 2 | pages = 121–32 | year = 2000 | pmid = 10936469 | doi = 10.1016/s1040-8428(00)00051-2}}</ref> It has a much lower risk of hepatotoxicity than [[flutamide]] and {{abbr|CPA|cyproterone acetate}} and of interstitial pneumonitis than [[nilutamide]].<ref name="pmid15604569">{{cite journal | vauthors = Thole Z, Manso G, Salgueiro E, Revuelta P, Hidalgo A | title = Hepatotoxicity induced by antiandrogens: a review of the literature | journal = Urol. Int. | volume = 73 | issue = 4 | pages = 289–95 | year = 2004 | pmid = 15604569 | doi = 10.1159/000081585 | s2cid = 24799765 }}</ref><ref name="pmid12603397a" /><ref name="pmid18657023" /><ref name="CRAIGFurr2010">{{cite book|vauthors=Craig JV, Furr BJ|title=Hormone Therapy in Breast and Prostate Cancer|url=https://books.google.com/books?id=dM0uvBnxiN0C&pg=PA356|date=5 February 2010|publisher=Springer Science & Business Media|isbn=978-1-59259-152-7|pages=356–|access-date=27 September 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114143135/https://books.google.com/books?id=dM0uvBnxiN0C&pg=PA356|url-status=live}}</ref><ref name="Bennett_2002">{{cite journal | vauthors = Bennett CL, Raisch DW, Sartor O | title = Pneumonitis associated with nonsteroidal antiandrogens: presumptive evidence of a class effect |journal=Annals of Internal Medicine | volume = 137 | issue = 7 | pages = 625 | date = October 2002 | pmid = 12353966 | doi = 10.7326/0003-4819-137-7-200210010-00029 | quote = An estimated 0.77% of the 6,480 nilutamide-treated patients, 0.04% of the 41,700 flutamide-treated patients, and 0.01% of the 86,800 bicalutamide-treated patients developed pneumonitis during the study period.}}</ref><ref name="pmid25270521">{{cite journal | vauthors = Ricci F, Buzzatti G, Rubagotti A, Boccardo F | title = Safety of antiandrogen therapy for treating prostate cancer | journal = Expert Opin Drug Saf | volume = 13 | issue = 11 | pages = 1483–99 | year = 2014 | pmid = 25270521 | doi = 10.1517/14740338.2014.966686 | s2cid = 207488100 }}</ref> The drug also does not share the unique risks of diarrhea with flutamide and nausea, vomiting, [[visual disturbance]]s, and [[alcohol intolerance]] with nilutamide.<ref name="pmid12603397a" /><ref name="Aronson2009" /><ref name="CRAIGFurr2010" /> Unlike [[enzalutamide]], bicalutamide is not associated with [[seizure]]s or related [[central nervous system|central]] side effects like anxiety and [[insomnia]].<ref name="pmid20878947">{{cite journal | vauthors = Foster WR, Car BD, Shi H, Levesque PC, Obermeier MT, Gan J, Arezzo JC, Powlin SS, Dinchuk JE, Balog A, Salvati ME, Attar RM, Gottardis MM | title = Drug safety is a barrier to the discovery and development of new androgen receptor antagonists | journal = Prostate | volume = 71 | issue = 5 | pages = 480–8 | year = 2011 | pmid = 20878947 | doi = 10.1002/pros.21263 | s2cid = 24620044 }}</ref><ref name="pmid24881730">{{cite journal | vauthors = Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B | title = Enzalutamide in metastatic prostate cancer before chemotherapy | journal = N. Engl. J. Med. | volume = 371 | issue = 5 | pages = 424–33 | year = 2014 | pmid = 24881730 | pmc = 4418931 | doi = 10.1056/NEJMoa1405095 }}</ref> However, although the risk of adverse liver changes with bicalutamide is low, enzalutamide differs from bicalutamide in having no known risk of elevated liver enzymes or hepatotoxicity.<ref name="pmid25711765">{{cite journal | vauthors = Keating GM | title = Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer | journal = Drugs Aging | volume = 32 | issue = 3 | pages = 243–9 | year = 2015 | pmid = 25711765 | doi = 10.1007/s40266-015-0248-y | s2cid = 29563345 }}</ref><ref name="pmid25354111">{{cite journal | vauthors = Beer TM, Tombal B | title = Enzalutamide in metastatic prostate cancer before chemotherapy | journal = N. Engl. J. Med. | volume = 371 | issue = 18 | pages = 1755–6 | year = 2014 | pmid = 25354111 | doi = 10.1056/NEJMc1410239 | url = https://iris.unito.it/bitstream/2318/150443/1/ENZALUTAMIDE.pdf | hdl = 2318/150443 | hdl-access = free | access-date = 23 September 2019 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828003253/https://iris.unito.it/retrieve/handle/2318/150443/144124/ENZALUTAMIDE.pdf | url-status = live }}</ref> In contrast to the {{abbr|SAA|steroidal antiandrogen}} [[spironolactone]], bicalutamide does not have [[antimineralocorticoid]] effects,<ref name="pmid8560673">{{cite journal | vauthors = Furr BJ, Tucker H | title = The preclinical development of bicalutamide: pharmacodynamics and mechanism of action | journal = Urology | volume = 47 | issue = 1A Suppl | pages = 13–25; discussion 29–32 | year = 1996 | pmid = 8560673 | doi = 10.1016/S0090-4295(96)80003-3}}</ref> and hence is not associated with [[hyperkalemia]], [[urinary frequency]], [[dehydration]], [[hypotension]], or other related side effects.<ref name="LenzShulman2010">{{cite journal |vauthors=Lenz AM, Shulman D, Eugster EA, Rahhal S, Fuqua JS, Pescovitz OH, Lewis KA |title=Bicalutamide and third-generation aromatase inhibitors in testotoxicosis |journal=Pediatrics |volume=126 |issue=3 |pages=e728-33 |date=September 2010 |pmid=20713483 |pmc=4096839 |doi=10.1542/peds.2010-0596}}</ref><ref name="Greenblatt1973">{{cite journal |vauthors=Greenblatt DJ, Koch-Weser J |title=Adverse reactions to spironolactone. A report from the Boston Collaborative Drug Surveillance Program |journal=JAMA |volume=225 |issue=1 |pages=40–3 |date=July 1973 |pmid=4740303 |doi=10.1001/jama.1973.03220280028007}}</ref><ref name="MunozCruz2014">{{cite book |vauthors=Munoz R, da Cruz E, Vetterly CG, Cooper D, Berry D |title=Handbook of Pediatric Cardiovascular Drugs |url=https://books.google.com/books?id=wwPnAwAAQBAJ&pg=PA224 |date=26 June 2014 |publisher=Springer |isbn=978-1-4471-2464-1 |pages=224– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143136/https://books.google.com/books?id=wwPnAwAAQBAJ&pg=PA224 |url-status=live }}</ref><ref name="Aronson2009" /> In women, unlike {{abbr|CPA|cyproterone acetate}} and spironolactone, bicalutamide does not produce [[menstrual irregularity]] or [[amenorrhea]] and does not interfere with [[ovulation]] or [[fertility]].<ref name="pmid24455796"/><ref name="BahceciTuzcu2004">{{cite journal |vauthors=Bahceci M, Tuzcu A, Canoruc N, Tuzun Y, Kidir V, Aslan C |title=Serum C-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance |journal=Hormone Research |volume=62 |issue=6 |pages=283–7 |year=2004 |pmid=15542929 |doi=10.1159/000081973|s2cid=46261843 }}</ref>

==Overdose==
A single oral dose of bicalutamide in humans that results in symptoms of overdose or that is considered to be life-threatening has not been established.<ref name="FDALabel" /><ref name="Springhouse2000">{{cite book |title=Nurse Practitioner's Drug Handbook |url=https://books.google.com/books?id=I6Jt1THMB_4C |year=2000 |publisher=Springhouse Corp. |isbn=9780874349979 |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143136/https://books.google.com/books?id=I6Jt1THMB_4C |url-status=live }}</ref> Dosages of up to 600&nbsp;mg/day have been well tolerated in clinical trials,<ref name="TYRRElLIversen2006" /> and it is notable that there is a saturation of absorption with bicalutamide such that circulating levels of its active (''R'')-enantiomer do not further increase above a dosage of 300&nbsp;mg/day.<ref name="Cockshott2004" /><ref name="TYRRElLIversen2006" /> Overdose is considered unlikely to be life-threatening with bicalutamide or other first-generation {{abbr|NSAAs|nonsteroidal antiandrogens}} (i.e., flutamide and nilutamide).<ref name="Griffith2008">{{cite book | vauthors = Griffith HW |title=Complete Guide to Prescription & Nonprescription Drugs 2009 |url=https://books.google.com/books?id=YhAAet8Er4oC&pg=PA62 |year=2008 |publisher=HP Books |isbn=978-0-399-53463-8 |pages=62–|quote=Overdose unlikely to threaten life [with NSAAs].}}</ref> A massive overdose of nilutamide (13 grams, or 43 times the normal maximum 300&nbsp;mg/day clinical dosage) in a 79-year-old man was uneventful, producing no clinical signs, symptoms, or toxicity.<ref name="Genrx1999">{{cite book |author=Genrx |title=1999 Mosby's GenRx |url=https://books.google.com/books?id=Td6ZFsVsCswC |year=1999 |publisher=Mosby |isbn=978-0-323-00625-5 |quote=A 79-year-old man attempted suicide by ingesting 13g of nilutamide (i.e., 43 times the maximum recommended dose). Despite immediate gastric lavage and oral administration of activated charcoal, plasma nilutamide levels peaked at 6 times the normal range 2 hours after ingestion. There were no clinical signs or symptoms or changes in parameters such as transaminases or chest x-ray. Maintenance treatment (150 mg/day) was resumed 30 days later.}}</ref> There is no specific [[antidote]] for bicalutamide or {{abbr|NSAA|nonsteroidal antiandrogen}} overdose, and treatment should be based on symptoms, if any are present.<ref name="FDALabel" /><ref name="Springhouse2000" />

==Interactions==
Bicalutamide is almost exclusively [[metabolized]] by [[CYP3A4]].<ref name="LemkeWilliams2008" /> As such, its levels in the body may be altered by [[enzyme inhibitor|inhibitors]] and [[enzyme inducer|inducers]] of CYP3A4.<ref name="Skidmore-Roth2013">{{cite book |vauthors=Skidmore-Roth L |title=Mosby's 2014 Nursing Drug Reference – Elsevieron VitalSource |url=https://books.google.com/books?id=ISYiAQAAQBAJ&pg=PA194 |date=17 April 2013 |publisher=Elsevier Health Sciences |isbn=978-0-323-22267-9 |pages=193–194 |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143136/https://books.google.com/books?id=ISYiAQAAQBAJ&pg=PA194 |url-status=live }}</ref> (For a list of CYP3A4 inhibitors and inducers, see [[CYP3A4#Ligands|here]].) However, in spite of the fact bicalutamide is metabolized by CYP3A4, there is no evidence of clinically significant [[drug interaction]]s when bicalutamide at a dosage of 150&nbsp;mg/day or less is co-administered with drugs that inhibit or induce [[cytochrome P450]] [[enzyme]] activity.<ref name="Wellington2006" />

''[[In-vitro]]'' studies suggest that bicalutamide may be able to inhibit CYP3A4 and, to a lesser extent, [[CYP2C9]], [[CYP2C19]], and [[CYP2D6]].<ref name="Cockshott2004" /> Conversely, animal studies suggest that bicalutamide may induce cytochrome P450 enzymes.<ref name="Cockshott2004" /> In a clinical study, bicalutamide co-administered with the CYP3A4 substrate midazolam caused only a small and statistically non-significant increase in midazolam levels (+27%) presumably due to CYP3A4 inhibition.<ref name="Cockshott2004" /> However, this was well below increases in midazolam exposure with potent CYP3A4 inhibitors like [[ketoconazole]] (+1500%), [[itraconazole]] (+1000%), and [[erythromycin]] (+350%), and is considered to not be clinically important.<ref name="Cockshott2004" /> There is no indication of clinically significant enzyme inhibition or induction with bicalutamide at doses of 150{{nbsp}}mg/day or below.<ref name="Cockshott2004" />

Because bicalutamide circulates at relatively high concentrations and is highly protein-bound, it has the potential to displace other highly protein-bound drugs like [[warfarin]], [[phenytoin]], [[theophylline]], and [[aspirin]] from [[binding protein|plasma binding proteins]].<ref name="WirthHakenberg2007" /><ref name="Kolvenbag1996" /> This could, in turn, result in increased free concentrations of such drugs and increased effects and/or side effects, potentially necessitating dosage adjustments.<ref name="WirthHakenberg2007" /> Bicalutamide has specifically been found to displace [[coumarin]] [[anticoagulant]]s like warfarin from their plasma binding proteins (namely [[human serum albumin|albumin]]) ''[[in vitro]]'', potentially resulting in an increased anticoagulant effect. This is supported by reports of prolonged [[prothrombin]] time and internal bleeding after the introduction of bicalutamide in patients previously stable on coumarin anticoagulants.<ref name="FDALabel" /> Close monitoring of prothrombin time and dosage adjustment as necessary is recommended when bicalutamide is used in combination with these drugs.<ref name="Weber2015">{{cite book | vauthors = Weber GF |title=Molecular Therapies of Cancer |url=https://books.google.com/books?id=dhs_CgAAQBAJ&pg=PA318 |date=22 July 2015 |publisher=Springer |isbn=978-3-319-13278-5 |pages=318–|quote=Compared to flutamide and nilutamide, bicalutamide has a 2-fold increased affinity for the Androgen Receptor, a longer half-life, and substantially reduced toxicities. Based on a more favorable safety profile relative to flutamide, bicalutamide is indicated for use in combination therapy with a Gonadotropin Releasing Hormone analog for the treatment of advanced metastatic prostate carcinoma.}}</ref><ref name="Mosby2001">{{cite book |title=Mosby's GenRx: A Comprehensive Reference for Generic and Brand Prescription Drugs |url=https://books.google.com/books?id=QxsobYYgm8oC |year=2001 |publisher=Mosby |isbn=978-0-323-00629-3 |page=290 |quote=In vitro studies have shown bicalutamide can displace coumarin anticoagulants, such as warfarin, from their protein-binding sites. It is recommended that if bicalutamide is started in patients already receiving coumarin anticoagulants, prothrombin times should be closely monitored and adjustment of the anticoagulant dose may be necessary.}}</ref><ref name="SprattoWoods2008">{{cite book |vauthors=Spratto G, Woods A |title=2009 Edition Delmar's Nurse's Drug Handbook |url=https://books.google.com/books?id=8MoIHiUja_oC&pg=PA175 |date=2 July 2008 |publisher=Cengage Learning |isbn=978-1-4283-6106-5 |pages=175– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143137/https://books.google.com/books?id=8MoIHiUja_oC&pg=PA175 |url-status=live }}</ref> However, in spite of this, no conclusive evidence of an interaction between bicalutamide and other drugs was found in clinical trials of nearly 3,000 patients.<ref name="Kolvenbag1996" />

==Pharmacology==

===Pharmacodynamics===
{{Main|Pharmacology of bicalutamide#Pharmacodynamics}}

====Antiandrogenic activity====
Bicalutamide acts as a highly [[binding selectivity|selective]] [[competitive antagonist|competitive]] [[silent antagonist]] of the {{abbr|AR|androgen receptor}} ({{abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 159–243&nbsp;nM), the major [[biological target]] of the [[androgen]] [[sex hormone]]s [[testosterone]] and {{abbrlink|DHT|dihydrotestosterone}}, and hence is an [[antiandrogen]].<ref name="SinghGauthier2000" /><ref name="Balaji2016">{{cite book | vauthors = Balaj KC |title=Managing Metastatic Prostate Cancer In Your Urological Oncology Practice |url=https://books.google.com/books?id=1U4WDAAAQBAJ&pg=PA25 |date=25 April 2016 |publisher=Springer |isbn=978-3-319-31341-2 |pages=24–25 |url-status=live |archive-url=https://web.archive.org/web/20170908222331/https://books.google.com/books?id=1U4WDAAAQBAJ&pg=PA25 |archive-date=8 September 2017 |df=dmy-all}}</ref><ref name="MasielloCheng2002">{{cite journal |vauthors=Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP |title=Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor |journal=The Journal of Biological Chemistry |volume=277 |issue=29 |pages=26321–6 |date=July 2002 |pmid=12015321 |doi=10.1074/jbc.M203310200|doi-access=free }}</ref><ref name="Denis2012">{{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=PT128 |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-45745-6 |pages=128, 158, 203 |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143137/https://books.google.com/books?id=jqZDBQAAQBAJ&pg=PT128 |url-status=live }}</ref> The [[biological activity|activity]] of bicalutamide lies in the (''R'')-isomer.<ref name="SchellensMcLeod2005" /> Due to its selectivity for the {{abbr|AR|androgen receptor}}, bicalutamide does not interact importantly with other [[steroid hormone receptor]]s and hence has no clinically relevant [[off-target activity|off-target]] hormonal activity (e.g., [[progestogen]]ic, [[estrogen (medication)|estrogen]]ic, [[glucocorticoid]], [[antimineralocorticoid]]).<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=PA1208 |year=2001 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-1750-2 |pages=1119, 1196, 1208 |url-status=live |archive-url=https://web.archive.org/web/20170908222331/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1208 |archive-date=8 September 2017 |df=dmy-all}}</ref><ref name="FurrTucker1996">{{cite journal |vauthors=Furr BJ, Tucker H |title=The preclinical development of bicalutamide: pharmacodynamics and mechanism of action |journal=Urology |volume=47 |issue=1A Suppl |pages=13–25; discussion 29–32 |date=January 1996 |pmid=8560673 |doi=10.1016/S0090-4295(96)80003-3}}</ref><ref name="SchellensMcLeod2005">{{cite book | vauthors = Schellens JH, McLeod HL, Newell DR |title=Cancer Clinical Pharmacology |url=https://books.google.com/books?id=co8Sgu9N0FMC&pg=PA229 |date=5 May 2005 |publisher=OUP Oxford |isbn=978-0-19-262966-1 |pages=229–230 |url-status=live |archive-url=https://web.archive.org/web/20160610134202/https://books.google.com/books?id=co8Sgu9N0FMC&pg=PA229 |archive-date=10 June 2016 |df=dmy-all}}</ref><ref name="BagatellBremner2003">{{cite book | vauthors = Bagatelle C, Bremner WJ |title=Androgens in Health and Disease |url=https://books.google.com/books?id=vDcBCAAAQBAJ&pg=PA25 |date=27 May 2003 |publisher=Springer Science & Business Media |isbn=978-1-59259-388-0 |pages=25–}}</ref> However, it has been reported that bicalutamide has weak affinity for the [[progesterone receptor]] (PR), where it is an antagonist, and hence it could have some [[antiprogestogen]]ic activity.<ref name="pmid29497605">{{cite journal | vauthors = Ito Y, Sadar MD | title = Enzalutamide and blocking androgen receptor in advanced prostate cancer: lessons learnt from the history of drug development of antiandrogens | journal = Res Rep Urol | volume = 10 | pages = 23–32 | date = 2018 | pmid = 29497605 | pmc = 5818862 | doi = 10.2147/RRU.S157116 | doi-access = free }}</ref> Bicalutamide does not [[enzyme inhibitor|inhibit]] [[5α-reductase]] nor is known to inhibit other [[enzyme]]s involved in androgen [[steroidogenesis]] (e.g., [[CYP17A1]]).<ref name="Furr1995" /> Although it does not bind to the [[estrogen receptor]]s (ERs), bicalutamide can increase [[estrogen]] levels secondarily to {{abbr|AR|androgen receptor}} blockade when used as a monotherapy in males, and hence can have some ''indirect'' [[estrogen (medication)|estrogen]]ic effects in males.<ref name="pmid18231613">{{cite journal |vauthors=Guise TA, Oefelein MG, Eastham JA, Cookson MS, Higano CS, Smith MR |title=Estrogenic side effects of androgen deprivation therapy |journal=Reviews in Urology |volume=9 |issue=4 |pages=163–80 |year=2007 |pmid=18231613 |pmc=2213888 }}</ref> Bicalutamide neither suppresses nor inhibits androgen [[biosynthesis|production]] in the body (i.e., it does not act as an [[antigonadotropin]] or [[androgen steroidogenesis inhibitor]] or lower androgen levels) and hence exclusively mediates its antiandrogenic effects by antagonizing the {{abbr|AR|androgen receptor}}.<ref name="Dart2004" /><ref name="Becker2001" /><ref name="SchellensMcLeod2005" /> In addition to the classical [[nuclear receptor|nuclear]] {{abbr|AR|androgen receptor}}, bicalutamide has been assessed at the [[membrane androgen receptor]]s (mARs) and found to act as a potent antagonist of [[ZIP9]] ({{abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 66.3&nbsp;nM), whereas it does not appear to interact with [[GPRC6A]].<ref name="pmid28943399">{{cite journal | vauthors = Bulldan A, Malviya VN, Upmanyu N, Konrad L, Scheiner-Bobis G | title = Testosterone/bicalutamide antagonism at the predicted extracellular androgen binding site of ZIP9 | journal = Biochim. Biophys. Acta | volume = 1864 | issue = 12 | pages = 2402–2414 | year = 2017 | pmid = 28943399 | doi = 10.1016/j.bbamcr.2017.09.012 | doi-access = free }}</ref><ref name="pmid20947496">{{cite journal | vauthors = Pi M, Parrill AL, Quarles LD | title = GPRC6A mediates the non-genomic effects of steroids | journal = J. Biol. Chem. | volume = 285 | issue = 51 | pages = 39953–64 | year = 2010 | pmid = 20947496 | pmc = 3000977 | doi = 10.1074/jbc.M110.158063 | doi-access = free }}</ref>

The [[affinity (pharmacology)|affinity]] of bicalutamide for the {{abbr|AR|androgen receptor}} is relatively low as it is approximately 30 to 100&nbsp;times lower than that of {{abbr|DHT|dihydrotestosterone}}, which is 2.5- to 10-fold as potent as an {{abbr|AR|androgen receptor}} agonist as testosterone in [[bioassay]]s and is the main [[endogenous]] [[ligand (biochemistry)|ligand]] of the [[receptor (biochemistry)|receptor]] in the [[prostate gland]].<ref name="Furr2009">{{cite journal |vauthors=Furr BJ |title=Research on reproductive medicine in the pharmaceutical industry |journal=Human Fertility |volume=1 |issue=1 |pages=56–63 |year=2009 |pmid=11844311 |doi=10.1080/1464727982000198131}}</ref><ref name="Denis2012" /><ref name="Cockshott2004" /><ref name="pmid19359544">{{cite journal | vauthors = Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL | title = Development of a second-generation antiandrogen for treatment of advanced prostate cancer | journal = Science | volume = 324 | issue = 5928 | pages = 787–90 | year = 2009 | pmid = 19359544 | pmc = 2981508 | doi = 10.1126/science.1168175 | bibcode = 2009Sci...324..787T | quote = [...] bicalutamide has relatively low affinity for AR (at least 30-fold reduced relative to the natural ligand dihydrotestosterone (DHT)) (7), [...]}}</ref> However, typical clinical dosages of bicalutamide result in circulating levels of the drug that are thousands of times higher than those of testosterone and {{abbr|DHT|dihydrotestosterone}}, allowing it to powerfully prevent them from binding to and activating the receptor.<ref name="Furr1997">{{cite journal| vauthors = Furr BK |title=Relative potencies of flutamide and 'Casodex'|journal=Endocrine-Related Cancer|volume=4|issue=2|year=1997|pages=197–202|issn=1351-0088|doi=10.1677/erc.0.0040197}}</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=PA56 |date=14 September 2010 |publisher=Springer Science & Business Media |isbn=978-1-60327-829-4 |pages=56, 71–72, 75, 93 |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143137/https://books.google.com/books?id=4KDrjeWA5-UC&pg=PA56 |url-status=live }}</ref><ref name="FurrTucker1996" /><ref name="pmid8717469">{{cite journal |vauthors=Furr BJ |title=The development of Casodex (bicalutamide): preclinical studies |journal=European Urology |volume=29 | issue = Suppl 2 |pages=83–95 |year=1996 |pmid=8717469 |doi=10.1159/000473846}}</ref><ref name="FDALabel" /><ref name="TGALabel" /><ref name="DenisMahler1996" /><ref name="Wellington2006" /><ref name="pmid15838655">{{cite journal |vauthors=Boccardo F, Rubagotti A, Conti G, Potenzoni D, Manganelli A, Del Monaco D |title=Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer |journal=Cancer Chemotherapy and Pharmacology |volume=56 |issue=4 |pages=415–20 |year=2005 |pmid=15838655 |doi=10.1007/s00280-005-1016-1 |s2cid=23014567 |url=https://www.researchgate.net/publication/7897958 |access-date=11 December 2019 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828003250/https://www.researchgate.net/publication/7897958_Exploratory_study_of_drug_plasma_levels_during_bicalutamide_150_mg_therapy_co-administered_with_tamoxifen_or_anastrozole_for_prophylaxis_of_gynecomastia_and_breast_pain_in_men_with_prostate_cancer |url-status=live }}</ref> This is especially true in the case of surgical or medical castration, in which testosterone levels in the circulation are approximately 95% reduced and {{abbr|DHT|dihydrotestosterone}} levels in the prostate gland are about 50 to 60% reduced.<ref name="Denis2012" /><ref name="LuoMartel1997">{{cite journal |vauthors=Luo S, Martel C, Chen C, Labrie C, Candas B, Singh SM, Labrie F |title=Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity |journal=Urology |volume=50 |issue=6 |pages=913–9 |date=December 1997 |pmid=9426723 |doi=10.1016/S0090-4295(97)00393-2}}</ref> In women, levels of testosterone are substantially lower (20- to 40-fold) than in men,<ref name="MelmedPolonsky2015">{{cite book |vauthors=Melmed S, Polonsky KS, Reed Larsen P, Kronenberg HM |title=Williams Textbook of Endocrinology |url=https://books.google.com/books?id=YZ8_CwAAQBAJ&pg=PA704 |date=30 November 2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-29738-7 |pages=704–708, 711, 1104}}</ref> so much smaller doses of bicalutamide (e.g., 25&nbsp;mg/day in the hirsutism studies) are necessary.<ref name="WilliamsBigby2009" /><ref name="pmid24455796" /><ref name="MorettiGuccione2016">{{cite conference | title = Efficacy and Safety of Myo-Inositol Supplementation in the Treatment of Obese Hirsute PCOS Women: Comparative Evaluation with OCP+Bicalutamide Therapy | vauthors = Moretti C, Guccione L, Di Giacinto P, Simonelli I, Exacoustos C, Toscano V, Motta C, De Leo V, Petraglia F, Lenzi A | date = April 2016 | url = https://endo.confex.com/endo/2016endo/webprogram/Paper26631.html | conference = ENDO 2016 | location = Boston, Massachusetts | access-date = 1 February 2020 | archive-date = 1 February 2020 | archive-url = https://web.archive.org/web/20200201071020/https://endo.confex.com/endo/2016endo/webprogram/Paper26631.html | url-status = dead }}</ref><ref name="MahlerVerhelst1998" />

Blockade of the {{abbr|AR|androgen receptor}} by bicalutamide in the [[pituitary gland]] and [[hypothalamus]] results in prevention of the [[negative feedback]] of androgens on the [[hypothalamic–pituitary–gonadal axis]] (HPG axis) in males and consequent disinhibition of pituitary [[luteinizing hormone]] (LH) [[secretion]].<ref name="IversenMelezinek2001">{{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 }}</ref> This, in turn, results in an increase in circulating {{abbr|LH|luteinizing hormone}} levels and activation of the gonadal production of testosterone and by extension production of [[estradiol]].<ref name="pmid7537602">{{cite journal |vauthors=Eri LM, Haug E, Tveter KJ |title=Effects on the endocrine system of long-term treatment with the non-steroidal anti-androgen Casodex in patients with benign prostatic hyperplasia |journal=British Journal of Urology |volume=75 |issue=3 |pages=335–40 |date=March 1995 |pmid=7537602 |doi=10.1111/j.1464-410X.1995.tb07345.x}}</ref> Levels of testosterone have been found to increase 1.5- to 2-fold (59–97% increase) and levels of estradiol about 1.5- to 2.5-fold (65–146% increase) in men treated with 150&nbsp;mg/day bicalutamide monotherapy.<ref name="IIIBarbieri2013a" /><ref name="MarcusFeldman2007">{{cite book | vauthors = Marcus R, Feldman D, Nelson D, Rosen CJ |title=Osteoporosis |url=https://books.google.com/books?id=blFlkDHffW8C&pg=PA1354 |date=8 November 2007 |publisher=Academic Press |isbn=978-0-08-055347-4 |pages=1354–|url-status=live |archive-url=https://web.archive.org/web/20160611031603/https://books.google.com/books?id=blFlkDHffW8C&pg=PA1354 |archive-date=11 June 2016 |df=dmy-all}}</ref><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=405–17 |date=May 1998 |pmid=9592622 |doi=10.2165/00003088-199834050-00005|s2cid=25200595 }}</ref> In addition to testosterone and estradiol, there are smaller increases in concentrations of {{abbr|DHT|dihydrotestosterone}}, [[sex hormone-binding globulin]], and [[prolactin]].<ref name="MahlerVerhelst1998" /> Estradiol levels with bicalutamide monotherapy are similar to those in the low-normal [[premenopause|premenopausal]] female range while testosterone levels generally remain in the high end of the normal male range.<ref name="MarcusFeldman2007" /><ref name="WeinKavoussi2011">{{cite book | vauthors = Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA |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=2938–2939, 2946 |url-status=live |archive-url=https://web.archive.org/web/20160505225217/https://books.google.com/books?id=fu3BBwAAQBAJ&pg=PA2939 |archive-date=5 May 2016 |df=dmy-all}}</ref><ref name="Becker2001" /> Testosterone concentrations do not typically exceed the normal male range due to negative feedback on the {{abbr|HPG|hypothalamic–pituitary–gonadal}} axis by the increased concentrations of estradiol.<ref name="IversenMelezinek2001" /> Bicalutamide influences the {{abbr|HPG|hypothalamic–pituitary–gonadal}} axis and increases hormone levels only in men and not also in women.<ref name="Diamanti-KandarakisNestler2009">{{cite book | vauthors = Diamanti-Kandarakis E, Nestler JE, Pandas D, Pasquale R |title=Insulin Resistance and Polycystic Ovarian Syndrome: Pathogenesis, Evaluation, and Treatment |url=https://books.google.com/books?id=7ej6ZgqiFEsC&pg=PA75 |date=21 December 2009 |publisher=Springer Science & Business Media |isbn=978-1-59745-310-3 |pages=75–|url-status=live |archive-url=https://web.archive.org/web/20160519021821/https://books.google.com/books?id=7ej6ZgqiFEsC&pg=PA75 |archive-date=19 May 2016 |df=dmy-all}}</ref><ref name="CarrellPeterson2010">{{cite book | vauthors = Carrell DT, Peterson CW |title=Reproductive Endocrinology and Infertility: Integrating Modern Clinical and Laboratory Practice |url=https://books.google.com/books?id=lcBEheiufVcC&pg=PA163 |date=23 March 2010 |publisher=Springer Science & Business Media |isbn=978-1-4419-1436-1 |pages=163–|url-status=live |archive-url=https://web.archive.org/web/20140704201613/http://books.google.com/books?id=lcBEheiufVcC&pg=PA163 |archive-date=4 July 2014 |df=dmy-all}}</ref><ref name="BouchardCaraty1993">{{cite book | vauthors = Bouchard P, Caraty A |title=GnRH, GnRH Analogs, Gonadotropins and Gonadal Peptides |url=https://books.google.com/books?id=uctURfWwTb4C&pg=PA455 |date=15 November 1993 |publisher=CRC Press |isbn=978-0-203-09205-7 |pages=455–456 |quote=[...] when male levels of androgens are achieved in plasma, their effects on gonadotropin secretion are similar in women and men. [...] administration of flutamide in a group of normally-cycling women produced a clinical improvement of acne and hirsutism without any significant hormonal change. [...] All these data emphasize that physiological levels of androgens have no action on the regulation of gonadotropins in normal women. [...] Androgens do not directly play a role in gonadotropin regulation [in women].}}</ref> This is due to the much lower levels of androgens in women and their lack of basal suppression of the {{abbr|HPG|hypothalamic–pituitary–gonadal}} axis in this sex.<ref name="Diamanti-KandarakisNestler2009" /><ref name="CarrellPeterson2010" /><ref name="BouchardCaraty1993" /> As evidenced by its effectiveness in the treatment of prostate cancer and other androgen-dependent conditions, the antiandrogenic actions of bicalutamide considerably exceed any impact of the increased levels of testosterone it results in.<ref name="ChabnerLongo2010" /> However, the elevated levels of estradiol remain unopposed by bicalutamide and are responsible for the gynecomastia and feminizing side effects it causes in men.<ref name="pmid18062751">{{cite journal |vauthors=Sieber PR |title=Treatment of bicalutamide-induced breast events |journal=Expert Review of Anticancer Therapy |volume=7 |issue=12 |pages=1773–9 |date=December 2007 |pmid=18062751 |doi=10.1586/14737140.7.12.1773|s2cid=40410461 }}</ref> Although bicalutamide monotherapy increases gonadotropin and sex hormone levels in men, this will not occur if bicalutamide is combined with an antigonadotropin such as a {{abbr|GnRH|gonadotropin-releasing hormone}} analogue, estrogen, or [[progestogen]], as these medications maintain negative feedback on the HPG axis.<ref name="Melmed2016">{{cite book| vauthors = Melmed S |title=Williams Textbook of Endocrinology|url=https://books.google.com/books?id=YZ8_CwAAQBAJ&pg=PA752|date=1 January 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-29738-7|pages=752–|quote=GnRH analogues, both agonists and antagonists, severely suppress endogenous gonadotropin and testosterone production [...] Administration of GnRH agonists (e.g., leuprolide, goserelin) produces an initial stimulation of gonadotropin and testosterone secretion (known as a "flare"), which is followed in 1 to 2 weeks by GnRH receptor downregulation and marked suppression of gonadotropins and testosterone to castration levels. [...] To prevent the potential complications associated with the testosterone flare, AR antagonists (e.g., bicalutamide) are usually coadministered with a GnRH agonist for men with metastatic prostate cancer.399}}</ref><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=361–3 |year=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=731–7 |year=1988 |pmid=3143862 |doi=10.1016/0022-4731(88)90024-6}}</ref>

{{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy, including with bicalutamide, shows a number of tolerability differences from methods of androgen deprivation therapy that incorporate surgical or medical castration. For example, the rates of hot flashes, depression, fatigue, and sexual dysfunction are all much higher with {{abbr|GnRH|gonadotropin-releasing hormone}} analogues than with {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy. It is thought that this is because {{abbr|GnRH|gonadotropin-releasing hormone}} analogues suppress estrogen production in addition to androgen production, resulting in [[estrogen deficiency]].<ref name="WibowoSchellhammer2011">{{cite journal |vauthors=Wibowo E, Schellhammer P, Wassersug RJ |title=Role of estrogen in normal male function: clinical implications for patients with prostate cancer on androgen deprivation therapy |journal=The Journal of Urology |volume=185 |issue=1 |pages=17–23 |date=January 2011 |pmid=21074215 |doi=10.1016/j.juro.2010.08.094}}</ref><ref name="MotofeiRowland2011">{{cite journal |vauthors=Motofei IG, Rowland DL, Popa F, Kreienkamp D, Paunica S |title=Preliminary study with bicalutamide in heterosexual and homosexual patients with prostate cancer: a possible implication of androgens in male homosexual arousal |journal=BJU International |volume=108 |issue=1 |pages=110–5 |date=July 2011 |pmid=20955264 |doi=10.1111/j.1464-410X.2010.09764.x|s2cid=45482984 }}</ref><ref name="pmid23484454">{{cite journal |vauthors=Wibowo E, Wassersug RJ |title=The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy |journal=Critical Reviews in Oncology/Hematology |volume=87 |issue=3 |pages=224–38 |date=September 2013 |pmid=23484454 |doi=10.1016/j.critrevonc.2013.01.006}}</ref> In contrast, {{abbr|NSAA|nonsteroidal antiandrogen}} monotherapy does not decrease estrogen levels and in fact increases them, resulting in an excess of estrogens that compensates for androgen deficiency and allows for a preservation of mood, energy, and sexual function.<ref name="WibowoSchellhammer2011" /><ref name="MotofeiRowland2011" /><ref name="pmid23484454" /> [[Neurosteroid]]s that are produced from testosterone like [[3α-androstanediol]] and [[3β-androstanediol]], which are {{abbrlink|ERβ|estrogen receptor beta}} agonists and the former a potent [[GABAA receptor|GABA<sub>A</sub> receptor]] [[positive allosteric modulator]], may also be involved.<ref name="King2008">{{cite journal |vauthors=King SR |title=Emerging roles for neurosteroids in sexual behavior and function |journal=Journal of Andrology |volume=29 |issue=5 |pages=524–33 |year=2008 |pmid=18567641 |doi=10.2164/jandrol.108.005660|doi-access=free }}</ref><ref name="pmid7803627">{{cite journal |vauthors=Morali G, Oropeza MV, Lemus AE, Perez-Palacios G |title=Mechanisms regulating male sexual behavior in the rat: role of 3 alpha- and 3 beta-androstanediols |journal=Biology of Reproduction |volume=51 |issue=3 |pages=562–71 |date=September 1994 |pmid=7803627 |doi=10.1095/biolreprod51.3.562|doi-access=free }}</ref><ref name="pmid20646182">{{cite journal |vauthors=Sánchez Montoya EL, Hernández L, Barreto-Estrada JL, Ortiz JG, Jorge JC |title=The testosterone metabolite 3α-diol enhances female rat sexual motivation when infused in the nucleus accumbens shell |journal=The Journal of Sexual Medicine |volume=7 |issue=11 |pages=3598–609 |date=November 2010 |pmid=20646182 |pmc=4360968 |doi=10.1111/j.1743-6109.2010.01937.x}}</ref><ref name="Chedrese2009">{{cite book | vauthors = Chedrese PJ |title=Reproductive Endocrinology: A Molecular Approach |url=https://books.google.com/books?id=3FJXUN6Vh44C&pg=PA233 |date=13 June 2009 |publisher=Springer Science & Business Media |isbn=978-0-387-88186-7 |pages=233–|url-status=live |archive-url=https://web.archive.org/web/20170905040216/https://books.google.com/books?id=3FJXUN6Vh44C |archive-date=5 September 2017 |df=dmy-all}}</ref><ref name="pmid20552051">{{cite journal |vauthors=Frye CA, Edinger KL, Lephart ED, Walf AA |title=3alpha-androstanediol, but not testosterone, attenuates age-related decrements in cognitive, anxiety, and depressive behavior of male rats |journal=Frontiers in Aging Neuroscience |volume=2 |pages=15 |year=2010 |pmid=20552051 |pmc=2874398 |doi=10.3389/fnagi.2010.00015|doi-access=free }}</ref><ref name="HuangZhu2008">{{cite journal |vauthors=Huang Q, Zhu H, Fischer DF, Zhou JN |title=An estrogenic effect of 5alpha-androstane-3beta, 17beta-diol on the behavioral response to stress and on CRH regulation |journal=Neuropharmacology |volume=54 |issue=8 |pages=1233–8 |date=June 2008 |pmid=18457850 |doi=10.1016/j.neuropharm.2008.03.016|s2cid=9052079 }}</ref><ref name="FryeKoonce2008">{{cite journal |vauthors=Frye CA, Koonce CJ, Edinger KL, Osborne DM, Walf AA |title=Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice |journal=Hormones and Behavior |volume=54 |issue=5 |pages=726–34 |date=November 2008 |pmid=18775724 |pmc=3623974 |doi=10.1016/j.yhbeh.2008.07.013}}</ref> In the specific case of sexual dysfunction, an additional possibility for the difference is that without concomitant suppression of androgen production, blockade of the {{abbr|AR|androgen receptor}} by the bicalutamide in the brain is incomplete and insufficient to markedly influence sexual function.<ref name="pmid9592622">{{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 | quote = If used in monotherapy, libido and potency are largely preserved. Although the mechanisms to explain this are not completely understood, it seems that at the central level pure antiandrogens are unable to completely inhibit the effect of the increased amount of androgens. | s2cid = 25200595 }}</ref>

Under normal circumstances, bicalutamide has no capacity to activate the {{abbr|AR|androgen receptor}}.<ref name="pmid25797385">{{cite journal |vauthors=Bambury RM, Scher HI |title=Enzalutamide: Development from bench to bedside |journal=Urologic Oncology |volume=33 |issue=6 |pages=280–8 |date=June 2015 |pmid=25797385 |doi=10.1016/j.urolonc.2014.12.017}}</ref><ref name="BamburyRathkopf2015">{{cite journal |vauthors=Bambury RM, Rathkopf DE |title=Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide |journal=Urologic Oncology |volume=34 |issue=8 |pages=348–55 |date=August 2016 |pmid=26162486 |doi=10.1016/j.urolonc.2015.05.025}}</ref> However, in prostate cancer, [[genetic mutation|mutation]]s and overexpression of the {{abbr|AR|androgen receptor}} can accumulate in prostate gland cells which can convert bicalutamide from an antagonist of the {{abbr|AR|androgen receptor}} into an [[agonist]].<ref name="pmid25797385" /><ref name="pmid24100689">{{cite journal |vauthors=Pinto Á |title=Beyond abiraterone: new hormonal therapies for metastatic castration-resistant prostate cancer |journal=Cancer Biology & Therapy |volume=15 |issue=2 |pages=149–55 |date=February 2014 |pmid=24100689 |pmc=3928129 |doi=10.4161/cbt.26724}}</ref> This can result in paradoxical stimulation of prostate cancer growth with bicalutamide and is responsible for the phenomenon of the [[antiandrogen withdrawal syndrome]], where antiandrogen discontinuation paradoxically slows the rate of prostate cancer growth.<ref name="pmid25797385" /><ref name="pmid24100689" />

In transgender women, breast development is a desired effect of antiandrogen or estrogen treatment.<ref name="WierckxGooren2014" /><ref name="OrentreichDurr1974">{{cite journal | vauthors = Orentreich N, Durr NP | title = Proceedings: Mammogenesis in transsexuals | journal = The Journal of Investigative Dermatology | volume = 63 | issue = 1 | pages = 142–146 | date = July 1974 | pmid = 4365991 | doi = 10.1111/1523-1747.ep12678272 | doi-access = free }}</ref> Breast development and gynecomastia induced by bicalutamide is thought to be mediated by increased activation of the {{abbr|ER|estrogen receptor}} secondary to blockade of the {{abbr|AR|androgen receptor}} (resulting in disinhibition of the {{abbr|ER|estrogen receptor}} in breast tissue) and increased levels of estradiol.<ref name="JamesonGroot2015" /><ref name="IIIBarbieri2013b">{{cite book | vauthors = Strauss III JF, Barbieri RL |title=Yen and Jaffe's Reproductive Endocrinology |url=https://books.google.com/books?id=KZ95AAAAQBAJ&pg=PA236 |date=13 September 2013 |publisher=Elsevier Health Sciences |isbn=978-1-4557-2758-2 |pages=236–237 |url-status=live |archive-url=https://web.archive.org/web/20170114164554/https://books.google.com/books?id=KZ95AAAAQBAJ&pg=PA236 |archive-date=14 January 2017 |df=dmy-all}}</ref><ref name="WilsonNizet2015">{{cite book | vauthors = Wilson CB, Nizet V, Maldonado Y, Klein JO, Remington JS  |title=Remington and Klein's Infectious Diseases of the Fetus and Newborn Infant |url=https://books.google.com/books?id=VuZ1BwAAQBAJ&pg=PA190 |year=2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-24147-2 |pages=190–|url-status=live |archive-url=https://web.archive.org/web/20170114165129/https://books.google.com/books?id=VuZ1BwAAQBAJ&pg=PA190 |archive-date=14 January 2017 |df=dmy-all}}</ref> In addition to [[fat deposition]], [[connective tissue]] growth, and [[lactiferous duct|ductal]] development, bicalutamide has been found to produce moderate [[mammary alveolus|lobuloalveolar]] development of the breasts.<ref name="KanhaiHage2000">{{cite journal | vauthors = Kanhai RC, Hage JJ, van Diest PJ, Bloemena E, Mulder JW | title = Short-term and long-term histologic effects of castration and estrogen treatment on breast tissue of 14 male-to-female transsexuals in comparison with two chemically castrated men | journal = The American Journal of Surgical Pathology | volume = 24 | issue = 1 | pages = 74–80 | date = January 2000 | pmid = 10632490 | doi = 10.1097/00000478-200001000-00009 | s2cid = 37752666 | doi-access = free }}</ref><ref name="Lawrence2007">{{cite book | veditors = Meyer IH, Northridge ME |editor2-link=Mary Northridge |date=2006 |publisher=Springer |location=New York |isbn=978-0-387-28871-0 |chapter=Transgender Health Concerns | vauthors = Lawrence AA |title=The Health of Sexual Minorities |pages=476 |doi=10.1007/978-0-387-31334-4_19}}</ref><ref name="Rosen2009">{{cite book | vauthors = Rosen PP |title=Rosen's Breast Pathology |url=https://books.google.com/books?id=_swaovkfRMMC&pg=PA31 |year=2009 |publisher=Lippincott Williams & Wilkins |location=Philadelphia |isbn=978-0-7817-7137-5 |pages=31–|edition=3}}</ref> However, full lobuloalveolar maturation necessary for [[lactation]] and [[breastfeeding]] will not occur without progestogen treatment.<ref name="KanhaiHage2000" /><ref name="Lawrence2007" /><ref name="Rosen2009" />

Bicalutamide monotherapy seems to have minimal effect on [[testicle|testicular]] [[spermatogenesis]], testicular [[ultrastructure]], and certain aspects of [[male fertility]].<ref name="Mulhall2013">{{cite book | vauthors = Mulhall JP |title=Fertility Preservation in Male Cancer Patients |url=https://books.google.com/books?id=97wgAwAAQBAJ&pg=PA84 |date=21 February 2013 |publisher=Cambridge University Press |isbn=978-1-139-61952-3 |pages=84–|url-status=live |archive-url=https://web.archive.org/web/20160429171718/https://books.google.com/books?id=97wgAwAAQBAJ&pg=PA84 |archive-date=29 April 2016 |df=dmy-all}}</ref><ref name="IswaranImai1997" /><ref name="MorganteGradini2001">{{cite journal |vauthors=Morgante E, Gradini R, Realacci M, Sale P, D'Eramo G, Perrone GA, Cardillo MR, Petrangeli E, Russo M, Di Silverio F |title=Effects of long-term treatment with the anti-androgen bicalutamide on human testis: an ultrastructural and morphometric study |journal=Histopathology |volume=38 |issue=3 |pages=195–201 |date=March 2001 |pmid=11260298 |doi=10.1046/j.1365-2559.2001.01077.x|hdl=11573/387981 |s2cid=36892099 }}</ref> This seems to be because testosterone levels in the testes (where ~95% of testosterone in males is produced) are extremely high (up to 200-fold higher than circulating levels) and only a small fraction (less than 10%) of the normal levels of testosterone in the testes are actually necessary to maintain spermatogenesis.<ref name="SchillComhaire2006">{{cite book | vauthors = Schill W, Comhaire FH, Hargreave TB |title=Andrology for the Clinician |url=https://books.google.com/books?id=5Ts_AAAAQBAJ&pg=PA76 |date=26 August 2006 |publisher=Springer Science & Business Media |isbn=978-3-540-33713-3 |pages=76–|url-status=live |archive-url=https://web.archive.org/web/20160526220017/https://books.google.com/books?id=5Ts_AAAAQBAJ&pg=PA76 |archive-date=26 May 2016 |df=dmy-all}}</ref><ref name="NieschlagBehre2012">{{cite book |vauthors=Nieschlag E, Behre HM |title=Testosterone: Action – Deficiency – Substitution |url=https://books.google.com/books?id=jn3nCAAAQBAJ&pg=PA276 |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-72185-4 |pages=130, 276 |access-date=3 November 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143138/https://books.google.com/books?id=jn3nCAAAQBAJ&pg=PA276 |url-status=live }}</ref><ref name="Cheng2009">{{cite book |vauthors=Cheng CY |title=Molecular Mechanisms in Spermatogenesis |url=https://books.google.com/books?id=tdpVNN80_r0C&pg=PA258 |date=24 October 2009 |publisher=Springer Science & Business Media |isbn=978-0-387-09597-4 |pages=258– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143140/https://books.google.com/books?id=tdpVNN80_r0C&pg=PA258 |url-status=live }}</ref> As a result, bicalutamide appears to not be able to compete with testosterone in this sole part of the body to an extent sufficient to considerably interfere with androgen signaling and function.<ref name="SchillComhaire2006" /><ref name="NieschlagBehre2012" /><ref name="Cheng2009" /> However, while bicalutamide does not seem to be able to adversely influence testicular spermatogenesis, it may interfere with {{abbr|AR|androgen receptor}}-dependent sperm maturation and transport outside of the testes in the [[epididymis|epididymides]] and [[vas deferens]] where androgen levels are far lower, and hence may still be able to impair male fertility.<ref name="NeumannSchenck1980">{{cite book| vauthors = Neumann F, Schenck B |title=Regulation of Male Fertility|chapter=Antiandrogens: Basic Concepts and Clinical Trials|year=1980|pages=93–106|publisher=Springer |doi=10.1007/978-94-009-8875-0_10|chapter-url=https://books.google.com/books?id=AXArBgAAQBAJ&pg=PA93|isbn=978-94-009-8877-4}}</ref> In addition, the combination of bicalutamide with other medications, such as estrogens, progestogens, and {{abbr|GnRH|gonadotropin-releasing hormone}} analogues, can compromise spermatogenesis due to their own adverse effects on male fertility.<ref name="Johnson2003">{{cite book | vauthors = Johnson LR |title=Essential Medical Physiology |url=https://books.google.com/books?id=Ql10m-_q3nMC&pg=PA731 |date=14 October 2003 |publisher=Academic Press |isbn=978-0-08-047270-6 |pages=731–|url-status=live |archive-url=https://web.archive.org/web/20170215093206/https://books.google.com/books?id=Ql10m-_q3nMC&pg=PA731 |archive-date=15 February 2017 |df=dmy-all}}</ref><ref name="JonesReiter2016">{{cite journal | vauthors = Jones CA, Reiter L, Greenblatt E |title=Fertility preservation in transgender patients |journal=International Journal of Transgenderism |volume=17 |issue=2 |year=2016 |pages=76–82 |issn=1553-2739 |doi=10.1080/15532739.2016.1153992 |s2cid=58849546 |quote=Traditionally, patients have been advised to cryopreserve sperm prior to starting cross-sex hormone therapy as there is a potential for a decline in sperm motility with high-dose estrogen therapy over time (Lubbert et al., 1992). However, this decline in fertility due to estrogen therapy is controversial due to limited studies.}}</ref><ref name="PayneHardy2007">{{cite book | vauthors = Payne AH, Hardy MP |title=The Leydig Cell in Health and Disease |url=https://books.google.com/books?id=x4ttqKIAOg0C&pg=PA422 |date=28 October 2007 |publisher=Springer Science & Business Media |isbn=978-1-59745-453-7 |pages=422–431 |quote=Estrogens are highly efficient inhibitors of the hypothalamic-hypophyseal-testicular axis (212–214). Aside from their negative feedback action at the level of the hypothalamus and pituitary, direct inhibitory effects on the testis are likely (215,216). [...] The histology of the testes [with estrogen treatment] showed disorganization of the seminiferous tubules, vacuolization and absence of lumen, and compartmentalization of spermatogenesis.}}</ref><ref name="WakelinMaibach2002">{{cite book | vauthors = Wakelin SH, Maibach HI, Archer CB |title=Systemic Drug Treatment in Dermatology: A Handbook |url=https://books.google.com/books?id=F1ZiAgAAQBAJ&pg=PA32 |date=1 June 2002 |publisher=CRC Press |isbn=978-1-84076-013-2 |pages=32–|quote=[Cyproterone acetate] inhibits spermatogenesis and produces reversible infertility (but is not a male contraceptive). |url-status=live |archive-url=https://web.archive.org/web/20140725205131/http://books.google.com/books?id=F1ZiAgAAQBAJ&pg=PA32 |archive-date=25 July 2014 |df=dmy-all}}</ref><ref name="pmid8005205">{{cite journal |vauthors=Neumann F |title=The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research |journal=Exp. Clin. Endocrinol. |volume=102 |issue=1 |pages=1–32 |year=1994 |pmid=8005205 |doi=10.1055/s-0029-1211261 |quote=Spermatogenesis is also androgen-dependent and is inhibited by CPA, meaning that patients treated with high doses of CPA are sterile (Figure 23). All the effects of CPA are fully reversible.|doi-access=free }}</ref><ref name="Salam2003">{{cite book | vauthors = Salam MA |title=Principles & Practice of Urology: A Comprehensive Text |url=https://books.google.com/books?id=y50kTcCCfEcC&pg=PA684 |year=2003 |publisher=Universal-Publishers |isbn=978-1-58112-412-5 |pages=684–|quote=Estrogens act primarily through negative feedback at the hypothalamic-pituitary level to reduce LH secretion and testicular androgen synthesis. [...] Interestingly, if the treatment with estrogens is discontinued after 3 yr. of uninterrupted exposure, serum testosterone may remain at castration levels for up to another 3 yr. This prolonged suppression is thought to result from a direct effect of estrogens on the Leydig cells.}}</ref> These medications are able to strongly suppress gonadal androgen production, which can severely impair or abolish testicular spermatogenesis, and estrogens also appear to have direct and potentially long-lasting [[cytotoxic]] effects in the testes at sufficiently high concentrations.<ref name="Johnson2003" /><ref name="JonesReiter2016" /><ref name="PayneHardy2007" /><ref name="WakelinMaibach2002" /><ref name="pmid8005205" /><ref name="Salam2003" />

====Other activities====
Bicalutamide has been found to act as an [[enzyme inhibitor|inhibitor]] or [[enzyme inducer|inducer]] of certain [[cytochrome P450]] [[enzyme]]s including [[CYP3A4]], [[CYP2C9]], [[CYP2C19]], and [[CYP2D6]] in [[preclinical research]], but no evidence of this has been found in humans treated with up to 150&nbsp;mg/day.<ref name="Cockshott2004" /> It has also been identified ''[[in vitro]]'' as a strong inhibitor of [[CYP27A1]] (cholesterol 27-hydroxylase) and as an inhibitor of [[CYP46A1]] (cholesterol 24-hydroxylase), but this has yet to be assessed or confirmed ''[[in vivo]]'' or in humans and the clinical significance remains unknown.<ref name="pmid26082378">{{cite journal |vauthors=Mast N, Lin JB, Pikuleva IA |title=Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy |journal=Molecular Pharmacology |volume=88 |issue=3 |pages=428–36 |date=September 2015 |pmid=26082378 |doi=10.1124/mol.115.099598 |pmc=4551053}}</ref><ref name="MastZheng2013">{{cite journal |vauthors=Mast N, Zheng W, Stout CD, Pikuleva IA |title=Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response |journal=The Journal of Biological Chemistry |volume=288 |issue=7 |pages=4613–24 |date=February 2013 |pmid=23288837 |doi=10.1074/jbc.M112.438754 |pmc=3576067|doi-access=free }}</ref> Bicalutamide has been found to be a [[P-glycoprotein]] (ABCB1) inhibitor.<ref name="ZhuLiu2015">{{cite journal |vauthors=Zhu Y, Liu C, Armstrong C, Lou W, Sandher A, Gao AC |title=Antiandrogens Inhibit ABCB1 Efflux and ATPase Activity and Reverse Docetaxel Resistance in Advanced Prostate Cancer |journal=Clinical Cancer Research |volume=21 |issue=18 |pages=4133–42 |date=September 2015 |pmid=25995342 |doi=10.1158/1078-0432.CCR-15-0269 |pmc=4573793}}</ref><ref name="Fenner2015">{{cite journal |vauthors=Fenner A |title=Prostate cancer: Antiandrogens reverse docetaxel resistance via ABCB1 inhibition |journal=Nature Reviews. Urology |volume=12 |issue=7 |pages=361 |date=July 2015 |pmid=26057062 |doi=10.1038/nrurol.2015.135|s2cid=29729317 }}</ref><ref name="pmid26309896">{{cite journal |vauthors=Armstrong CM, Gao AC |title=Drug resistance in castration resistant prostate cancer: resistance mechanisms and emerging treatment strategies |journal=American Journal of Clinical and Experimental Urology |volume=3 |issue=2 |pages=64–76 |year=2015 |pmid=26309896 |pmc=4539108 }}</ref> Like other first-generation {{abbr|NSAAs|nonsteroidal antiandrogens}} and [[enzalutamide]], it has been found to act as a weak [[negative allosteric modulator|non-competitive inhibitor]] of [[GABAA receptor|GABA<sub>A</sub> receptor]]-mediated [[electric current|current]]s ''in vitro'' ({{abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 5.2&nbsp;μM).<ref name="FosterCar2011">{{cite journal |vauthors=Foster WR, Car BD, Shi H, Levesque PC, Obermeier MT, Gan J, Arezzo JC, Powlin SS, Dinchuk JE, Balog A, Salvati ME, Attar RM, Gottardis MM |title=Drug safety is a barrier to the discovery and development of new androgen receptor antagonists |journal=The Prostate |volume=71 |issue=5 |pages=480–8 |date=April 2011 |pmid=20878947 |doi=10.1002/pros.21263|s2cid=24620044 }}</ref><ref name="BarrishCarter2010">{{cite book |vauthors=Barrish J, Carter P, Cheng P |title=Accounts in Drug Discovery: Case Studies in Medicinal Chemistry |url=https://books.google.com/books?id=GlrOSAvRlJsC&pg=PA127 |year=2010 |publisher=Royal Society of Chemistry |isbn=978-1-84973-126-3 |pages=127– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143141/https://books.google.com/books?id=GlrOSAvRlJsC&pg=PA127 |url-status=live }}</ref> However, unlike enzalutamide, bicalutamide has not been found to be associated with [[seizure]]s or other related adverse [[central nervous system|central]] effects, so the clinical relevance of this finding is uncertain.<ref name="FosterCar2011" /><ref name="BarrishCarter2010" />

===Pharmacokinetics===
{{Main|Pharmacology of bicalutamide#Pharmacokinetics}}

Though its absolute [[bioavailability]] in humans is unknown, bicalutamide is known to be extensively and well-[[absorption (pharmacokinetics)|absorbed]].<ref name="Cockshott2004" /><ref name="Dart2004" /> Its absorption is not affected by [[food]].<ref name="Dart2004" /><ref name="Weber2015" /> The absorption of bicalutamide is linear at doses up to 150&nbsp;mg/day and is saturable at doses above this, with no further increases in [[steady state (pharmacokinetics)|steady-state levels]] of bicalutamide occurring at doses above 300&nbsp;mg/day.<ref name="Cockshott2004" /><ref name="Wellington2006" /><ref name="KolvenbagBlackledge1998">{{cite journal |vauthors=Kolvenbag GJ, Blackledge GR, Gotting-Smith K |title=Bicalutamide (Casodex) in the treatment of prostate cancer: history of clinical development |journal=The Prostate |volume=34 |issue=1 |pages=61–72 |date=January 1998 |pmid=9428389 |doi=10.1002/(SICI)1097-0045(19980101)34:1<61::AID-PROS8>3.0.CO;2-N|s2cid=22785559 |doi-access=free }}</ref><ref name="TYRRElLIversen2006">{{cite journal |vauthors=Tyrrell CJ, Iversen P, Tammela T, Anderson J, Björk T, Kaisary AV, Morris T |title=Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration |journal=BJU International |volume=98 |issue=3 |pages=563–72 |date=September 2006 |pmid=16771791 |doi=10.1111/j.1464-410X.2006.06275.x|s2cid=41672303 }}</ref> Whereas absorption of (''R'')-bicalutamide is slow, with levels [[Cmax (pharmacology)|peak]]ing at 31 to 39&nbsp;hours after a dose, (''S'')-bicalutamide is much more rapidly absorbed.<ref name="Wellington2006" /><ref name="FDALabel" /><ref name="Cockshott2004" /> Steady-state concentrations of the drug are reached after 4 to 12&nbsp;weeks of treatment independently of dosage, with a 10- to 20-fold progressive accumulation in levels of (''R'')-bicalutamide.<ref name="Wellington2006" /><ref name="pmid8717470">{{cite journal | vauthors = Blackledge GR | title = Clinical progress with a new antiandrogen, Casodex (bicalutamide) | journal = Eur. Urol. | volume = 29 | issue = Suppl 2 | pages = 96–104 | date = 1996 | pmid = 8717470 | doi = 10.1159/000473847 }}</ref><ref name="Jr.Lawrence2015">{{cite book | vauthors = DeVita Jr VT, Lawrence TS, Rosenberg SA |title=DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology |url=https://books.google.com/books?id=HEAYBgAAQBAJ&pg=PT1142 |date=7 January 2015 |publisher=Wolters Kluwer Health |isbn=978-1-4698-9455-3 |pages=1142–}}</ref><ref name="DenisMahler1996">{{cite journal |vauthors=Denis L, Mahler C |title=Pharmacodynamics and pharmacokinetics of bicalutamide: defining an active dosing regimen |journal=Urology |volume=47 |issue=1A Suppl |pages=26–8; discussion 29–32 |date=January 1996 |pmid=8560674 |doi=10.1016/S0090-4295(96)80004-5}}</ref> The long time to steady-state levels is the result of bicalutamide's very long [[elimination half-life]].<ref name="DenisMahler1996" /> There is wide [[interindividual variability]] in (''R'')-bicalutamide levels (up to 16-fold) with bicalutamide regardless of dosage.<ref name="Cockshott2004" />

The [[distribution (pharmacology)|tissue distribution]] of bicalutamide is not well-characterized.<ref name="ChuJr.2012">{{cite book |vauthors=Chu E, DeVita Jr VT |title=Physicians' Cancer Chemotherapy Drug Manual 2013 |url=https://books.google.com/books?id=E_Q8eIxYlHcC&pg=PA51 |date=28 December 2012 |publisher=Jones & Bartlett Publishers |isbn=978-1-284-04039-5 |pages=51– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143141/https://books.google.com/books?id=E_Q8eIxYlHcC&pg=PA51 |url-status=live }}</ref> The amount of bicalutamide in [[semen]] that could potentially be transferred to a female partner during [[sexual intercourse]] is low and is not thought to be important.<ref name="TGALabel" /> Based on [[animal research|animal studies]] with rats and dogs it was thought that bicalutamide could not cross the [[blood–brain barrier]] and hence could not enter the brain.<ref name="HelsenVan den Broeck2014">{{cite journal |vauthors=Helsen C, Van den Broeck T, Voet A, Prekovic S, Van Poppel H, Joniau S, Claessens F |title=Androgen receptor antagonists for prostate cancer therapy |journal=Endocrine-Related Cancer |volume=21 |issue=4 |pages=T105-18 |date=August 2014 |pmid=24639562 |doi=10.1530/ERC-13-0545|doi-access=free }}</ref><ref name="FurrTucker1996" /><ref name="Furr1989">{{cite journal |vauthors=Furr BJ |title="Casodex" (ICI 176,334)--a new, pure, peripherally-selective anti-androgen: preclinical studies |journal=Hormone Research |volume=32 | issue = Suppl 1 |pages=69–76 |year=1989 |pmid=2533159 |doi=10.1159/000181315}}</ref><ref name="FurrValcaccia1987">{{cite journal |vauthors=Furr BJ, Valcaccia B, Curry B, Woodburn JR, Chesterson G, Tucker H |title=ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen |journal=The Journal of Endocrinology |volume=113 |issue=3 |pages=R7-9 |date=June 1987 |pmid=3625091 |doi=10.1677/joe.0.113R007}}</ref> As such, it was initially thought to be a [[peripherally selective drug|peripherally selective]] antiandrogen.<ref name="HelsenVan den Broeck2014" /><ref name="FurrTucker1996" /> However, subsequent clinical studies found that this was not also the case for humans, indicating species differences; bicalutamide crosses into the human brain and, in accordance, produces effects and side effects consistent with central antiandrogenic action.<ref name="Cockshott2004" /><ref name="IversenMelezinek2001" /><ref name="SolowaySchellhammer1995">{{cite journal |vauthors=Soloway MS, Schellhammer PF, Smith JA, Chodak GW, Vogelzang NJ, Kennealey GT |title=Bicalutamide in the treatment of advanced prostatic carcinoma: a phase II noncomparative multicenter trial evaluating safety, efficacy and long-term endocrine effects of monotherapy |journal=The Journal of Urology |volume=154 |issue=6 |pages=2110–4 |date=December 1995 |pmid=7500470 |doi=10.1016/S0022-5347(01)66709-0}}</ref><ref name="GaoDalton2007">{{cite journal |vauthors=Gao W, Dalton JT |title=Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs) |journal=Drug Discovery Today |volume=12 |issue=5–6 |pages=241–8 |date=March 2007 |pmid=17331889 |pmc=2072879 |doi=10.1016/j.drudis.2007.01.003}}</ref><ref name="pmid16896883">{{cite journal |vauthors=Mason M |title=What implications do the tolerability profiles of antiandrogens and other commonly used prostate cancer treatments have on patient care? |journal=Journal of Cancer Research and Clinical Oncology |volume=132 |issue = Suppl 1 |pages=S27-35 |date=August 2006 |pmid=16896883 |doi=10.1007/s00432-006-0134-4|pmc=12161115 |s2cid=19685819 }}</ref> In any case, there is indication that bicalutamide might have at least some peripheral selectivity in humans.<ref name="pmid20682842">{{cite journal | vauthors = Veldhuis JD, Takahashi PY, Keenan DM, Liu PY, Mielke KL, Weist SM | title = Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men | journal = Am J Physiol Endocrinol Metab | volume = 299 | issue = 4 | pages = E675–82 | date = October 2010 | pmid = 20682842 | pmc = 2957871 | doi = 10.1152/ajpendo.00300.2010 | url = }}</ref> Bicalutamide is highly [[plasma protein binding|plasma protein bound]] (96.1% for racemic bicalutamide, 99.6% for (''R'')-bicalutamide) and is bound mainly to [[human serum albumin|albumin]], with negligible binding to {{abbr|SHBG|sex hormone-binding globulin}} and [[corticosteroid-binding globulin]].<ref name="LemkeWilliams2008" /><ref name="Cockshott2004" /><ref name="ChuJr.2012" /><ref name="Furr1995">{{cite journal |vauthors=Furr BJ |title=Casodex: preclinical studies and controversies |journal=Annals of the New York Academy of Sciences |volume=761 |issue=1 |pages=79–96 |date=June 1995 |pmid=7625752 |doi=10.1111/j.1749-6632.1995.tb31371.x|bibcode=1995NYASA.761...79F |s2cid=37242269 }}</ref>

Bicalutamide is [[metabolism|metabolized]] in the [[liver]].<ref name="LemkeWilliams2008" /><ref name="Weber2015" /> (''R'')-Bicalutamide is metabolized slowly and almost exclusively via [[hydroxylation]] by [[CYP3A4]] into (''R'')-hydroxybicalutamide.<ref name="Weber2015" /><ref name="Cockshott2004" /><ref name="LemkeWilliams2008" /><ref name="LemkeWilliams2012" /> This [[metabolite]] is then [[glucuronidation|glucuronidated]] by [[UGT1A9]].<ref name="Weber2015" /><ref name="Cockshott2004" /><ref name="GrosseCampeau2013">{{cite journal |vauthors=Grosse L, Campeau AS, Caron S, Morin FA, Meunier K, Trottier J, Caron P, Verreault M, Barbier O |title=Enantiomer selective glucuronidation of the non-steroidal pure anti-androgen bicalutamide by human liver and kidney: role of the human UDP-glucuronosyltransferase (UGT)1A9 enzyme |journal=Basic & Clinical Pharmacology & Toxicology |volume=113 |issue=2 |pages=92–102 |date=August 2013 |pmid=23527766 |pmc=3815647 |doi=10.1111/bcpt.12071 }}</ref><ref name="Schellhammer2005" /> In contrast to (''R'')-bicalutamide, (''S'')-bicalutamide is metabolized rapidly and mainly by glucuronidation (without hydroxylation).<ref name="Weber2015" /> None of the metabolites of bicalutamide are known to be active and levels of the metabolites are low in plasma, where unchanged biclautamide predominates.<ref name="LemkeWilliams2008" /><ref name="pmid8997470" /><ref name="Cockshott2004" /> Due to the stereoselective metabolism of bicalutamide, (''R'')-bicalutamide has a far longer terminal half-life than (''S'')-bicalutamide and its levels are about 10- to 20-fold higher in comparison following a single dose and 100-fold higher at steady-state.<ref name="Wellington2006" /><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=PA1372 |date=24 January 2012 |publisher=Lippincott Williams & Wilkins |isbn=978-1-60913-345-0 |pages=1372–1373 |url-status=live |archive-url=https://web.archive.org/web/20160503223616/https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1372 |archive-date=3 May 2016 |df=dmy-all}}</ref><ref name="ButlerGovindan2010">{{cite book |vauthors=Butler SK, Govindan R |title=Essential Cancer Pharmacology: The Prescriber's Guide |url=https://books.google.com/books?id=ZC0oMwt1ZKgC&pg=PA49 |date=25 October 2010 |publisher=Lippincott Williams & Wilkins |isbn=978-1-60913-704-5 |pages=49– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143143/https://books.google.com/books?id=ZC0oMwt1ZKgC&pg=PA49 |url-status=live }}</ref> (''R'')-Bicalutamide has a relatively long elimination half-life of 5.8&nbsp;days with a single dose and 7 to 10&nbsp;days following repeated administration.<ref name="JordanFurr2010">{{cite book | vauthors = Jordan VC, Furr BJ |title=Hormone Therapy in Breast and Prostate Cancer |url=https://books.google.com/books?id=dM0uvBnxiN0C&pg=PA350 |date=5 February 2010 |publisher=Springer Science & Business Media |isbn=978-1-59259-152-7 |pages=350–|url-status=live |archive-url=https://web.archive.org/web/20160529061703/https://books.google.com/books?id=dM0uvBnxiN0C&pg=PA350 |archive-date=29 May 2016 |df=dmy-all}}</ref>

Bicalutamide is [[elimination (pharmacology)|eliminated]] in similar proportions in [[feces]] (43%) and [[urine]] (34%), while its metabolites are eliminated roughly equally in [[urine]] and [[bile]].<ref name="LemkeWilliams2008" /><ref name="Weber2015" /><ref name="pmid14748655">{{cite journal |vauthors=Fradet Y |title=Bicalutamide (Casodex) in the treatment of prostate cancer |journal=Expert Review of Anticancer Therapy |volume=4 |issue=1 |pages=37–48 |date=February 2004 |pmid=14748655 |doi=10.1586/14737140.4.1.37 |s2cid=34153031 |quote=In contrast, the incidence of diarrhea was comparable between the bicalutamide and placebo groups (6.3 vs. 6.4%, respectively) in the EPC program [71].}}</ref><ref name="pmid22495777">{{cite journal |vauthors=Sharma K, Pawar GV, Giri S, Rajagopal S, Mullangi R |title=Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of bicalutamide in mouse plasma: application to a pharmacokinetic study |journal=Biomedical Chromatography |volume=26 |issue=12 |pages=1589–95 |year=2012 |pmid=22495777 |doi=10.1002/bmc.2736 }}</ref> The drug is [[excretion|excreted]] to a substantial extent in unmetabolized form, and both bicalutamide and its metabolites are eliminated mainly as [[glucuronide]] [[conjugation (biochemistry)|conjugate]]s.<ref name="SchellensMcLeod2005" /> The glucuronide conjugates of bicalutamide and its metabolites are eliminated from the circulation rapidly, unlike unconjugated bicalutamide.<ref name="Cockshott2004" /><ref name="Weber2015" /><ref name="AndersonKnoben2001">{{cite book | vauthors = Anderson PO, Knoben JE, Troutman WG |title=Handbook of Clinical Drug Data |series=Canadian Medical Association Journal |volume=128 |issue=12 |url=https://books.google.com/books?id=40UJmr_6WQ4C |date=22 August 2001 |publisher=McGraw Hill Professional |isbn=978-0-07-138942-6 |page=245 |quote=With an oral dose of 50 mg/day, bicalutamide attains a peak serum level of 8.9 mg/L (21 μmol/L) 31 hr after a dose at steady state. CI of (R)-bicalutamide is 0.32 L/hr. The active (R)-enantiomer of bicalutamide is oxidized to an inactive metabolite, which, like the inactive (S)-enantiomer, is glucuronidated and cleared rapidly by elimination in the urine and feces.165|pmid=20313924 |pmc=1875767 }}</ref>

The pharmacokinetics of bicalutamide are not affected by consumption of food, a person's age or body weight, [[renal impairment]], or mild-to-moderate [[hepatic impairment]].<ref name="Cockshott2004" /><ref name="DenisMahler1996" /> However, steady-state levels of bicalutamide are higher in [[Japanese people|Japanese individuals]] than in [[white people]].<ref name="Cockshott2004" />
{{Bicalutamide metabolism|align=center|caption=This diagram illustrates the primary metabolic pathways involved in the metabolism of bicalutamide in humans.}}

==Chemistry==
Bicalutamide is a [[racemic mixture]] consisting of equal proportions of enantiomers (''R'')-bicalutamide ([[dextrorotatory]]) and (''S'')-bicalutamide ([[levorotatory]]).<ref name="FDALabel" /> Its [[systematic name]] ([[IUPAC nomenclature of organic chemistry|{{abbr|IUPAC|International Union of Pure and Applied Chemistry}}]]) is (''RS'')-''N''-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide.<ref name="Publishing2013" /><ref name="KomstaWaksmundzka-Hajnos2013">{{cite book | vauthors = Komsta L, Waksmundzka-Hajnos M, Sherma J |title=Thin Layer Chromatography in Drug Analysis |url=https://books.google.com/books?id=LSEtAgAAQBAJ&pg=PA652 |date=20 December 2013 |publisher=CRC Press |isbn=978-1-4665-0715-9 |pages=652–}}</ref> The compound has a [[chemical formula]] of C<sub>18</sub>H<sub>14</sub>F<sub>4</sub>N<sub>2</sub>O<sub>4</sub>S, a [[molecular weight]] of 430.373&nbsp;g/mol, and is a fine white to off-white powder.<ref name="FDALabel" /><ref name="TGALabel">{{cite web |title=COSUDEX® (bicalutamide) 150 mg tablets |publisher=TGA |url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05200-3&d=2016081316114622483&d=2016083016114622483 |url-status=live |archive-url=https://web.archive.org/web/20160914231137/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05200-3&d=2016081316114622483&d=2016083016114622483 |archive-date=14 September 2016 |df=dmy-all}}</ref>

The [[acid dissociation constant]] (pKa') of bicalutamide is approximately 12.<ref name="TGALabel" /> It is a highly [[lipophilic]] compound ([[Partition coefficient#Partition coefficient and log P|log P]] = 2.92).<ref name="Cockshott2004" /><ref name="pmid21369450">{{cite journal |vauthors=Sancheti PP, Vyas VM, Shah M, Karekar P, Pore YV |title=Spectrophotometric estimation of bicalutamide in tablets |journal=Indian Journal of Pharmaceutical Sciences |volume=70 |issue=6 |pages=810–2 |year=2008 |pmid=21369450 |pmc=3040883 |doi=10.4103/0250-474X.49131 |doi-access=free }}</ref> At 37&nbsp;°C (98.6&nbsp;°F), or [[human body temperature|normal human body temperature]], bicalutamide is practically [[solubility|insoluble]] in water (4.6&nbsp;mg/L), [[acid]] (4.6&nbsp;mg/L at [[pH]] 1), and [[alkali]] (3.7&nbsp;mg/L at pH 8).<ref name="FDALabel" /><ref name="TGALabel" /> In [[organic solvent]]s, it is slightly soluble in [[chloroform]] and [[ethanol|absolute ethanol]], sparingly soluble in [[methanol]], and freely soluble in [[acetone]] and [[tetrahydrofuran]].<ref name="FDALabel" /><ref name="TGALabel" />

Bicalutamide is a [[synthetic compound|synthetic]] and [[nonsteroidal]] [[chemical compound|compound]] which was [[chemical derivative|derived]] from [[flutamide]].<ref name="MohlerBohl2009" /> It is a [[bicyclic compound]] (has two [[ring (chemistry)|ring]]s) and can be classified as and has variously been referred to as an [[anilide]] (''N''-[[phenyl group|phenyl]][[amide]]) or [[aniline]], a di[[aryl]][[propanamide|propionamide]], and a [[toluidide]].<ref name="MohlerBohl2009" /><ref name="LemkeWilliams2012" /> The crystalline structure of bicalutamide is represented by a wide variety of conformation-dependent solid forms,<ref>{{cite journal | vauthors = Sobornova VV, Belov KV, Krestyaninov MA, Khodov IA | title = Influence of Solvent Polarity on the Conformer Ratio of Bicalutamide in Saturated Solutions: Insights from NOESY NMR Analysis and Quantum-Chemical Calculations | journal = International Journal of Molecular Sciences | volume = 25 | issue = 15 | pages = 8254 | date = July 2024 | pmid = 39125824 | pmc = 11311660 | doi = 10.3390/ijms25158254 | doi-access = free }}</ref> including [[Crystal polymorphism|polymorphs]],<ref>{{cite journal | vauthors = Vega DR, Polla G, Martinez A, Mendioroz E, Reinoso M | title = Conformational polymorphism in bicalutamide | journal = International Journal of Pharmaceutics | volume = 328 | issue = 2 | pages = 112–118 | date = January 2007 | pmid = 16978811 | doi = 10.1016/j.ijpharm.2006.08.001 }}</ref> crystal solvates,<ref name=glp>{{Cite journal | vauthors = Perlovich GL, Blokhina SV, Manin NG, Volkova TV, Tkachev VV |date=January 2013 |title=Polymorphism and solvatomorphism of bicalutamide: Thermophysical study and solubility |url=http://link.springer.com/10.1007/s10973-012-2540-y |journal=Journal of Thermal Analysis and Calorimetry |language=en |volume=111 |issue=1 |pages=655–662 |doi=10.1007/s10973-012-2540-y |issn=1388-6150|url-access=subscription }}</ref> [[Cocrystal|co-crystals]],<ref>{{cite journal | vauthors = Bis JA, Vishweshwar P, Weyna D, Zaworotko MJ | title = Hierarchy of supramolecular synthons: persistent hydroxyl...pyridine hydrogen bonds in cocrystals that contain a cyano acceptor | journal = Molecular Pharmaceutics | volume = 4 | issue = 3 | pages = 401–416 | date = 2007-06-01 | pmid = 17500564 | doi = 10.1021/mp070012s }}</ref> and others. The developed structure of the aliphatic fragment promotes the formation of different conformers,<ref>{{Cite journal | vauthors = Mololina AA, Sobornova VV, Belov KV, Krestyaninov MA, Khodov IA |date=April 2025 |title=Role of non-covalent interactions in the conformational stability of bicalutamide in different solvent environments: Insights from quantum-chemical calculations and NMR spectroscopy |url=https://linkinghub.elsevier.com/retrieve/pii/S0167732225000790 |journal=Journal of Molecular Liquids |language=en |volume=423 |article-number=126921 |doi=10.1016/j.molliq.2025.126921|url-access=subscription }}</ref> thereby opening the potential for creating new solid forms with enhanced characteristics. For example, the bicalutamide solvate with [[Dimethyl sulfoxide|DMSO]] demonstrated a concentration increase of up to 3.3 times compared to form I. A similar trend is observed for the metastable form II and the amorphous state, with concentrations of approximately 3.0 × 10<sup>−7</sup> and 3.3 × 10<sup>−7</sup> [[Mole fraction|m.f.]], respectively, which are more than twice those of the stable form I.<ref name=glp/>

===Analogues===
{{See also|Discovery and development of antiandrogens}}

First-generation {{abbr|NSAAs|nonsteroidal antiandrogens}} including bicalutamide, [[flutamide]], and [[nilutamide]] are all synthetic, nonsteroidal anilide derivatives and [[structural analog]]ues of each other.<ref name="MohlerBohl2009">{{cite journal |vauthors=Mohler ML, Bohl CE, Jones A, Coss CC, Narayanan R, He Y, Hwang DJ, Dalton JT, Miller DD |title=Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit |journal=Journal of Medicinal Chemistry |volume=52 |issue=12 |pages=3597–617 |date=June 2009 |pmid=19432422 |doi=10.1021/jm900280m |quote=[C]linically relevant antiandrogens currently are nonsteroidal anilide derivatives. Antiandrogens used for prostate cancer include the monoarylpropionamide flutamide (1) (a prodrug of hydroxyflutamide (2)),29–31 the hydantoin nilutamide(3),32–34 and the diarylpropionamide bicalutamide (4) (Chart1).35–37}}</ref> Bicalutamide is a diarylpropionamide while flutamide is a monoarylpropionamide and nilutamide is a [[hydantoin]].<ref name="MohlerBohl2009" /> Bicalutamide and flutamide, though not nilutamide, can also be classified as toluidides.<ref name="LemkeWilliams2012" /> All three of the compounds share a common 3-[[trifluoromethyl]][[aniline]] moiety.<ref name="BéguéBonnet-Delpon2008">{{cite book |vauthors=Bégué J, Bonnet-Delpon D |title=Bioorganic and Medicinal Chemistry of Fluorine |url=https://books.google.com/books?id=QMVSvZ-R7I0C&pg=PA327 |date=2 June 2008 |publisher=John Wiley & Sons |isbn=978-0-470-28187-1 |pages=327– |access-date=27 September 2016 |archive-date=12 January 2023 |archive-url=https://web.archive.org/web/20230112173104/https://books.google.com/books?id=QMVSvZ-R7I0C&pg=PA327 |url-status=live }}</ref> Bicalutamide is a modification of flutamide in which a 4-[[fluoro]][[phenyl group|phenyl]][[sulfonyl]] moiety has been added and the nitro group on the original phenyl ring has been replaced with a cyano group.<ref name="BallKamalian2016">{{cite journal |vauthors=Ball AL, Kamalian L, Alfirevic A, Lyon JJ, Chadwick AE |title=Identification of the Additional Mitochondrial Liabilities of 2-Hydroxyflutamide When Compared With its Parent Compound, Flutamide in HepG2 Cells |journal=Toxicological Sciences |date=July 2016 |pmid=27413113 |doi=10.1093/toxsci/kfw126 |pages=341–351|pmc=5036617 |volume=153|issue=2 }}</ref> [[Topilutamide]], also known as fluridil, is another {{abbr|NSAA|nonsteroidal antiandrogen}} that is closely related structurally to the first-generation {{abbr|NSAAs|nonsteroidal antiandrogens}}, but, in contrast to them, is not used in the treatment of prostate cancer and is instead used exclusively as a [[topical]] antiandrogen in the treatment of pattern hair loss.<ref name="pmid16821162" /><ref name="AvramRogers2009">{{cite book |vauthors=Avram MR, Rogers NE |title=Hair Transplantation |url=https://books.google.com/books?id=j1XF1bnABFcC&pg=PA11 |date=30 November 2009 |publisher=Cambridge University Press |isbn=978-1-139-48339-1 |pages=11– |access-date=3 November 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143141/https://books.google.com/books?id=j1XF1bnABFcC&pg=PA11 |url-status=live }}</ref><ref name="HaberStough2006">{{cite book | vauthors = Haber RS, Stough DB |title=Hair Transplantation |url=https://books.google.com/books?id=PXJMqrbk-fAC&pg=PA6 |access-date=28 May 2012 |year=2006 |publisher=Elsevier Health Sciences |isbn=978-1-4160-3104-8 |pages=6–7 |url-status=live |archive-url=https://web.archive.org/web/20140704201433/http://books.google.com/books?id=PXJMqrbk-fAC&pg=PA6 |archive-date=4 July 2014 |df=dmy-all}}</ref>

{{Show
| head-align = center
| content-align = center
| Chemical structures of first-generation {{abbr|NSAAs|nonsteroidal antiandrogens}}
| <gallery widths="225px" heights="225px" class="center skin-invert-image">
 Image:Flutamide.svg|[[Flutamide]]
 Image:Nilutamide.svg|[[Nilutamide]]
 Image:Bicalutamide.svg|Bicalutamide
 Image:Topilutamide.svg|[[Topilutamide]]
</gallery>
}}

The second-generation {{abbr|NSAAs|nonsteroidal antiandrogens}} enzalutamide and [[apalutamide]] were derived from and are analogues of the first-generation {{abbr|NSAAs|nonsteroidal antiandrogens}},<ref name="Weber2015" /><ref name="KawaharaMiyamoto2014">{{cite journal | vauthors = Kawahara T, Minamoto H |title=Androgen Receptor Antagonists in the Treatment of Prostate Cancer |journal=Clinical Immunology, Endocrine & Metabolic Drugs |volume=1 |issue=1 |year=2014 |pages=11–19 |doi=10.2174/22127070114019990002}}</ref> while another second-generation {{abbr|NSAA|nonsteroidal antiandrogen}}, [[darolutamide]], is said to be structurally distinct and chemically unrelated to the other {{abbr|NSAAs|nonsteroidal antiandrogens}}.<ref name="pmid26137992">{{cite journal |vauthors=Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ |title=Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies |journal=Sci Rep |volume=5 |article-number=12007 |year=2015 |pmid=26137992 |pmc=4490394 |doi=10.1038/srep12007 |bibcode=2015NatSR...512007M }}</ref> Enzalutamide is a modification of bicalutamide in which the inter-ring linking [[side chain|chain]] has been altered and [[cyclic compound|cyclized]] into a 5,5-di[[methyl group|methyl]]-4-[[oxygen|oxo]]-2-[[thioxo]] [[imidazolidine]] moiety. In apalutamide, the 5,5-dimethyl groups of the imidazolidine ring of enzalutamide are cyclized to form an accessory [[cyclobutane]] ring and one of its phenyl rings is replaced with a [[pyridine]] ring.

{{Show
| head-align = center
| content-align = center
| Chemical structures of second-generation {{abbr|NSAAs|nonsteroidal antiandrogens}}
| <gallery widths="225px" heights="225px" class="center skin-invert-image">
 Image:Enzalutamide-01.svg|[[Enzalutamide]]
 Image:Apalutamide.svg|[[Apalutamide]]
 Image:Proxalutamide skeletal.svg|[[Proxalutamide]]
 Image:ODM-201.svg|[[Darolutamide]]
</gallery>
}}

The first nonsteroidal androgens, the arylpropionamides, were discovered via [[molecular modification|structural modification]] of bicalutamide.<ref name="SegalNarayanan2006">{{cite journal |vauthors=Segal S, Narayanan R, Dalton JT |title=Therapeutic potential of the SARMs: revisiting the androgen receptor for drug discovery |journal=Expert Opinion on Investigational Drugs |volume=15 |issue=4 |pages=377–87 |date=April 2006 |pmid=16548787 |doi=10.1517/13543784.15.4.377 |s2cid=31787187 |quote=Structural modifications of bicalutamide led to the discovery of the first nonsteroidal androgens (the aryl propionamides) in 1998. Lead compounds in this class (denoted S1 and S4 in published literature) not only bind to the AR with high affinity (low nanomolar range), but also demonstrate tissue selectivity in animal models [46,50].}}</ref> Unlike bicalutamide (which is purely antiandrogenic), these compounds show tissue-selective androgenic effects and were classified as [[selective androgen receptor modulator]]s (SARMs).<ref name="SegalNarayanan2006" /> Lead {{abbr|SARMs|selective androgen receptor modulator}} of this series included [[acetothiolutamide]], [[enobosarm]] (ostarine; S-22), and [[andarine]] (acetamidoxolutamide or androxolutamide; S-4).<ref name="MohlerBohl2009" /><ref name="SegalNarayanan2006" /><ref name="Yin2002">{{cite journal |vauthors=Yin D, Gao W, Kearbey JD, Xu H, Chung K, He Y, Marhefka CA, Veverka KA, Miller DD, Dalton JT |title=Pharmacodynamics of selective androgen receptor modulators |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=304 |issue=3 |pages=1334–40 |date=March 2003 |pmid=12604714 |pmc=2040238 |doi=10.1124/jpet.102.040840}}</ref> They are very close to bicalutamide structurally, with the key differences being that the linker sulfone of bicalutamide has been replaced with an [[ether]] or [[thioether]] group to confer agonism of the {{abbr|AR|androgen receptor}} and the 4-fluoro atom of the pertinent phenyl ring has been substituted with an [[acetamide|acetamido]] or cyano group to eliminate [[reactivity (chemistry)|reactivity]] at the position.<ref name="OttowWeinmann2008">{{cite book |vauthors=Ottow E, Weinmann H |title=Nuclear Receptors as Drug Targets |url=https://books.google.com/books?id=iATfLbPgRugC&pg=PA257 |date=8 September 2008 |publisher=John Wiley & Sons |isbn=978-3-527-62330-3 |pages=257–258 |access-date=1 December 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143143/https://books.google.com/books?id=iATfLbPgRugC&pg=PA257 |url-status=live }}</ref>

{{Show
| head-align = center
| content-align = center
| Chemical structures of arylpropionamide {{abbr|SARMs|selective androgen receptor modulators}}
| <gallery widths="225px" heights="225px" class="center skin-invert-image">
 Image:Acetothiolutamide.svg|[[Acetothiolutamide]]
 Image:Ostarine.svg|[[Enobosarm]]
 Image:Andarine.svg|[[Andarine]]
</gallery>
}}

A few [[radiolabeling|radiolabeled]] derivatives of bicalutamide have been developed for potential use as [[radiotracer]]s in [[medical imaging]].<ref name="pmid17328524">{{cite journal |vauthors=Parent EE, Dence CS, Jenks C, Sharp TL, Welch MJ, Katzenellenbogen JA |title=Synthesis and biological evaluation of [18F]bicalutamide, 4-[76Br]bromobicalutamide, and 4-[76Br]bromo-thiobicalutamide as non-steroidal androgens for prostate cancer imaging |journal=J. Med. Chem. |volume=50 |issue=5 |pages=1028–40 |year=2007 |pmid=17328524 |doi=10.1021/jm060847r }}</ref><ref name="DierckxOtte2014">{{cite book | vauthors = Dierckx RA, Otte A, de Vries EF, van Waarde A, Luiten PG |title=PET and SPECT of Neurobiological Systems |url=https://books.google.com/books?id=LN64BAAAQBAJ&pg=PA394 |date=15 February 2014 |publisher=Springer Science & Business Media |isbn=978-3-642-42014-6 |pages=394–}}</ref> They include [<sup>18</sup>F]bicalutamide, 4-[<sup>76</sup>Br]bromobicalutamide, and [<sup>76</sup>Br]bromo-thiobicalutamide.<ref name="pmid17328524" /><ref name="DierckxOtte2014" /> The latter two were found to have substantially increased affinity for the {{abbr|AR|androgen receptor}} relative to that of bicautamide.<ref name="pmid17328524" /> However, none of these agents have been evaluated in humans.<ref name="pmid17328524" /><ref name="DierckxOtte2014" />

[[5N-Bicalutamide|5''N''-Bicalutamide]], or 5-azabicalutamide, is a minor structural modification of bicalutamide which acts as a [[irreversible antagonist|reversible covalent antagonist]] of the {{abbr|AR|androgen receptor}} and has approximately 150-fold higher affinity for the {{abbr|AR|androgen receptor}} and about 20-fold greater functional inhibition of the {{abbr|AR|androgen receptor}} relative to bicalutamide.<ref name="pmid28981251">{{cite journal | vauthors = de Jesus Cortez F, Nguyen P, Truillet C, Tian B, Kuchenbecker KM, Evans MJ, Webb P, Jacobson MP, Fletterick RJ, England PM | title = Development of 5N-Bicalutamide, a High-Affinity Reversible Covalent Antiandrogen | journal = ACS Chem. Biol. | volume = 12| issue = 12| pages = 2934–2939| year = 2017 | pmid = 28981251 | doi = 10.1021/acschembio.7b00702 | s2cid = 24974359 }}</ref><ref name="US20170101384">{{cite patent |invent1=England, Pamela M.|invent2=Fletterick, R. J.|invent3=Kuchenbecker, K.|invent4=de Jesus Cortez, F. |pubdate=2016 |country=US |status=Patent |number=10053433B2}}</ref> It is among the most potent {{abbr|AR|androgen receptor}} antagonists to have been developed and is being researched for potential use in the treatment of antiandrogen-resistant prostate cancer.<ref name="pmid28981251" />

===Synthesis===
A number of [[chemical synthesis|chemical syntheses]] of bicalutamide have been published in the literature.<ref name="Publishing2013" /><ref name="pmid3361581">{{cite journal |vauthors=Tucker H, Crook JW, Chesterson GJ |title=Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides |journal=Journal of Medicinal Chemistry |volume=31 |issue=5 |pages=954–9 |year=1988 |pmid=3361581 |doi=10.1021/jm00400a011 }}</ref><ref name="JamesEkwuribe2002">{{cite journal | vauthors = James KD, Ekwuribe NN |title=A Two-step Synthesis of the Anti-cancer Drug (R,S)-Bicalutamide |journal=Synthesis |volume=2002 |issue=7 |year=2002 |pages=850–2 |doi=10.1055/s-2002-28508}}</ref><ref>{{cite patent |country=US |number=2006/0041161 |status=application |title=Procedure for the synthesis of bicalutamide |pubdate=23 February 2006 |fdate=24 May 2005 |pridate=17 June 2004 |inventor=Pizzetti E, Vigano E, Lussana M, Landonio E |url=https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=20060223&CC=US&NR=2006041161A1&KC=A1 }} {{Webarchive|url=https://web.archive.org/web/20180104090257/https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=20060223&CC=US&NR=2006041161A1&KC=A1 |date=4 January 2018 }}</ref><ref name="ChandShukla2012">{{cite report | vauthors = Chand M, Shukla AK |title=Novel Synthesis of Bicalutamide Drug Substance and their Impurities using Imidazolium Type of Ionic Liquid |year=2012 |doi=10.2139/ssrn.2160199 |doi-access=free |ssrn=2160199 }}</ref> The procedure of the first published synthesis of bicalutamide can be seen below.<ref name="pmid3361581" />
{{Annotated image 4|
|header=Bicalutamide synthesis<ref name="pmid3361581" />
|image=Bicalutamide synthesis.png
|class = skin-invert-image
|image-bg-color = light-dark(white,transparent)
|annot-color = var(--color-base,#202122)  
|align=center
|width=650
|height=277
|image-width=650
|caption=Where the starting material is [[4-cyano-3-(trifluoromethyl)aniline]] (also known as 4-amino-2-(trifluoromethyl)benzonitrile), DMA is [[dimethylacetamide]], and ''m''CPBA is [[meta-Chloroperoxybenzoic acid|''meta''-chloroperoxybenzoic acid]].
|alt=Bicalutamide chemical synthesis diagram
|annotations=
}}

==History==
Bicalutamide as well as all of the other currently marketed {{abbr|NSAAs|nonsteroidal antiandrogens}} were derived from structural modification of flutamide, which itself was originally synthesized as a [[bacteriostatic agent]] in 1967 at [[Schering-Plough|Schering Plough Corporation]] and was subsequently and serendipitously found to possess antiandrogenic activity.<ref name="Diamanti-Kandarakis_1999">{{cite journal |vauthors=Diamanti-Kandarakis E |title=Current aspects of antiandrogen therapy in women |journal=Current Pharmaceutical Design |volume=5 |issue=9 |pages=707–23 |date=September 1999 |doi=10.2174/1381612805666230111201150 |pmid=10495361 |url=https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA717 |quote=Several trials demonstrated complete clearing of acne with flutamide [62,77]. Flutamide used in combination with an [oral contraceptive], at a dose of 500mg/d, flutamide caused a dramatic decrease (80%) in total acne, seborrhea and hair loss score after only 3 months of therapy [53]. When used as a monotherapy in lean and obese PCOS, it significantly improves the signs of hyperandrogenism, hirsutism and particularly acne [48]. [...] flutamide 500mg/d combined with an [oral contraceptive] caused an increase in cosmetically acceptable hair density, in sex of seven women suffering from diffuse androgenetic alopecia [53]. |access-date=27 September 2016 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110085132/https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA717 |url-status=live |url-access=subscription }}</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=55,279–280 |url-status=live |archive-url=https://web.archive.org/web/20160603180141/https://books.google.com/books?id=GreZlojD-tYC&pg=PA280 |archive-date=3 June 2016 |df=dmy-all}}</ref><ref name="Elks2014-2">{{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=PA573 |date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=573–|url-status=live |archive-url=https://web.archive.org/web/20160515085843/https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA573 |archive-date=15 May 2016 |df=dmy-all}}</ref> Bicalutamide was discovered by Tucker and colleagues at [[Imperial Chemical Industries]] (ICI) in the 1980s and was selected for development from a group of over 2,000&nbsp;synthesized compounds.<ref name="pmid11844311">{{cite journal | vauthors = Furr BJ | title = Research on reproductive medicine in the pharmaceutical industry | journal = Hum Fertil (Camb) | volume = 1 | issue = 1 | pages = 56–63 | date = 1998 | pmid = 11844311 | doi = 10.1080/1464727982000198131 }}</ref><ref name="Furr1995" /><ref name="pmid16515480">{{cite journal |vauthors=Cadilla R, Turnbull P |title=Selective androgen receptor modulators in drug discovery: medicinal chemistry and therapeutic potential |journal=Curr Top Med Chem |volume=6 |issue=3 |pages=245–70 |year=2006 |pmid=16515480 |doi=10.2174/156802606776173456 |url=https://zenodo.org/record/1154960 |access-date=11 December 2019 |archive-date=18 August 2020 |archive-url=https://web.archive.org/web/20200818103846/https://zenodo.org/record/1154960 |url-status=live }}</ref><ref name="Publishing2013">{{cite book | vauthors = McPherson EM |publisher=William Andrew Publishing |title=Pharmaceutical Manufacturing Encyclopedia |edition=3rd |url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA627 |date=22 October 2013 |isbn=978-0-8155-1856-3 |pages=627, 1695 |url-status=live |archive-url=https://web.archive.org/web/20160609223817/https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA627 |archive-date=9 June 2016 |df=dmy-all}}</ref> It was first patented in 1982<ref name="EngelKleemann2014">{{cite book | vauthors = Engel J, Kleemann A, Kutscher B, Reichert D |title=Pharmaceutical Substances: Syntheses, Patents and Applications of the most relevant APIs |edition=5th |year=2009 |url=https://books.google.com/books?id=4lCGAwAAQBAJ&pg=PA153 |publisher=Thieme |isbn=978-3-13-179275-4 |pages=153–154}}</ref> and was first reported in the [[scientific literature]] in June 1987.<ref name="pmid3625091">{{cite journal |vauthors=Furr BJ, Valcaccia B, Curry B, Woodburn JR, Chesterson G, Tucker H |title=ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen |journal=The Journal of Endocrinology |volume=113 |issue=3 |pages=R7-9 |date=June 1987 |pmid=3625091 |doi=10.1677/joe.0.113r007}}</ref>

Bicalutamide was first studied in a [[Phases of clinical research#Phase I|phase I]] [[clinical trial]] in 1987<ref name="Kolvenbag1996" /> and the results of the first [[Phases of clinical research#Phase II|phase II]] clinical trial in prostate cancer were published in 1990.<ref name="pmid2094607">{{cite journal | vauthors = Newling DW | title = The response of advanced prostatic cancer to a new non-steroidal antiandrogen: results of a multicenter open phase II study of Casodex. European/Australian Co-operative Group | journal = European Urology | volume = 18| issue = Suppl 3 | pages = 18–21 | year = 1990 | pmid = 2094607 | doi = 10.1159/000463973 }}</ref> The pharmaceutical division of {{abbr|ICI|Imperial Chemical Industries}} was split out into an independent company called [[Zeneca]] in 1993, and in April and May 1995, Zeneca (now [[AstraZeneca]], after merging with [[Astra AB]] in 1999) began pre-approval marketing of bicalutamide for the treatment of prostate cancer in the {{abbr|U.S.|United States}}.<ref name="Patents1997">{{cite book |title=The United States Patents Quarterly |url=https://books.google.com/books?id=kNlKAQAAIAAJ |year=1997 |publisher=Associated Industry Publications |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143145/https://books.google.com/books?id=kNlKAQAAIAAJ |url-status=live }}</ref> It was first launched in the {{abbrlink|U.K.|United Kingdom}} in May 1995,<ref name="ChaurasiyaSingh2012">{{cite journal | vauthors = Chaurasiya A, Singh AK, Upadhyay SC, Asati D, Ahmad FJ, Mukherjee R, Khar |title=Lipidic Nanocarrier for Oral Bioavailability Enhancement of an Anticancer Agent: Formulation Design and Evaluation |journal=Advanced Science Letters |volume=11 |issue=1 |year=2012 |pages=43–52 |issn=1936-6612 |doi=10.1166/asl.2012.2170}}</ref> and was subsequently approved by the {{abbr|U.S.|United States}} {{abbr|FDA|Food and Drug Administration}} on 4 October 1995, for the treatment of prostate cancer at a dosage of 50&nbsp;mg/day in combination with a {{abbr|GnRH|gonadotropin-releasing hormone}} analogue.<ref name="Klotz2006">{{cite journal | vauthors = Klotz L | title = Combined androgen blockade: an update | journal = The Urologic Clinics of North America | volume = 33 | issue = 2 | pages = 161–6, v–vi | date = May 2006 | pmid = 16631454 | doi = 10.1016/j.ucl.2005.12.001 }}</ref><ref name="pmid26236143">{{cite journal | vauthors = Gohil K | title = Exciting Therapies Ahead in Prostate Cancer | journal = P & T | volume = 40 | issue = 8 | pages = 530–531 | date = August 2015 | pmid = 26236143 | pmc = 4517537 }}</ref>

Following its introduction for use in combination with a {{abbr|GnRH|gonadotropin-releasing hormone}} analogue, bicalutamide was developed as a monotherapy at a dosage of 150&nbsp;mg/day for the treatment of prostate cancer, and was approved for this indication in Europe, Canada, and a number of other countries in the late 1990s and early 2000s.<ref name="Wellington2006" /><ref name="Denis2012" /><ref name="pmid11502439">{{cite journal |vauthors=Kolvenbag GJ, Iversen P, Newling DW |title=Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer |journal=Urology |volume=58 |issue=2 Suppl 1 |pages=16–23 |year=2001 |pmid=11502439 |doi=10.1016/s0090-4295(01)01237-7 }}</ref><ref name="CarswellFiggitt2002">{{cite journal |vauthors=Carswell CI, Figgitt DP |title=Bicalutamide: in early-stage prostate cancer |journal=Drugs |volume=62 |issue=17 |pages=2471–79; discussion 2480–1 |year=2002 |pmid=12421104 |doi=10.2165/00003495-200262170-00006|s2cid=195690919 }}</ref> This application of bicalutamide was also under review by the {{abbr|FDA|Food and Drug Administration}} in the {{abbr|U.S.|United States}} in 2002,<ref name="JasminCapanna2005">{{cite book |vauthors=Jasmin C, Capanna R, Coia L, Coleman R, Saillant G |title=Textbook of Bone Metastases |url=https://books.google.com/books?id=7vPj2a_93tEC&pg=PA493 |date=27 September 2005 |publisher=John Wiley & Sons |isbn=978-0-470-01160-7 |pages=493– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143143/https://books.google.com/books?id=7vPj2a_93tEC&pg=PA493 |url-status=live }}</ref> but ultimately was not approved in this country.<ref name="ChabnerLongo2010" /> In Japan, bicalutamide is licensed at a dosage of 80&nbsp;mg/day alone or in combination with a {{abbr|GnRH|gonadotropin-releasing hormone}} analogue for prostate cancer.<ref name="SuzukiKamiya2008"/> The unique 80&nbsp;mg dosage of bicalutamide used in Japan was selected for development in this country on the basis of observed pharmacokinetic differences with bicalutamide in Japanese men.<ref name="pmid17199134">{{cite journal |vauthors=Usami M, Akaza H, Arai Y, Hirano Y, Kagawa S, Kanetake H, Naito S, Sumiyoshi Y, Takimoto Y, Terai A, Yoshida H, Ohashi Y |title=Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients |journal=Prostate Cancer Prostatic Dis. |volume=10 |issue=2 |pages=194–201 |year=2007 |pmid=17199134 |doi=10.1038/sj.pcan.4500934 |quote=In most countries, bicalutamide is given at a dose of 50 mg when used in combination with an LHRH-A. However, based on pharmacokinetic and pharmacodynamic data, the approved dose of bicalutamide in Japanese men is 80 mg per day.|doi-access=free }}</ref>

Subsequent to negative findings of bicalutamide monotherapy for {{abbr|LPC|localized prostate cancer}} in the {{abbr|EPC|Early Prostate Cancer}} clinical programme, approval of bicalutamide for use specifically in the treatment of {{abbr|LPC|localized prostate cancer}} was withdrawn in a number of countries<ref name="pmid18093474">{{cite journal |vauthors=Shahani R, Fleshner NE, Zlotta AR |title=Pharmacotherapy for prostate cancer: the role of hormonal treatment |journal=Discovery Medicine |volume=7 |issue=39 |pages=118–24 |year=2007 |pmid=18093474 |url=http://www.discoverymedicine.com/Rohan-Shahani/2009/07/29/pharmacotherapy-for-prostate-cancer-the-role-of-hormonal-treatment/ |access-date=13 August 2016 |archive-date=9 August 2020 |archive-url=https://web.archive.org/web/20200809085744/https://www.discoverymedicine.com/Rohan-Shahani/2009/07/29/pharmacotherapy-for-prostate-cancer-the-role-of-hormonal-treatment/ |url-status=live }}</ref> including the {{abbr|U.K.|United Kingdom}} (in October or November 2003)<ref name="BowsherCarter2008">{{cite book | vauthors = Bowsher W, Carter A |title=Challenges in Prostate Cancer |url=https://books.google.com/books?id=E3VNhLkqPmUC&pg=PA146 |date=15 April 2008 |publisher=John Wiley & Sons |isbn=978-1-4051-7177-9 |pages=146–}}</ref> and several other European countries and Canada (in August 2003).<ref name="Wellington2006" /><ref name="Nations2005">{{cite book |author=United Nations |title=Consolidated List of Products Whose Consumption And/or Sale Have Been Banned, Withdrawn, Severely Restricted Or Not Approved by Governments: Pharmaceuticals |url=https://books.google.com/books?id=SH80iutLs98C&pg=PA4 |year=2005 |publisher=United Nations Publications |isbn=978-92-1-130241-7 |pages=4–}}</ref><ref name="Bono2004">{{cite journal | vauthors = Bono AV |title=Overview of Current Treatment Strategies in Prostate Cancer |journal=European Urology Supplements |volume=3 |issue=1 |year=2004 |pages=2–7 |doi=10.1016/j.eursup.2003.12.002 |quote=The Canadian Health Authorities have withdrawn the approval for antiandrogen monotherapy with bicalutamide for the treatment of localised prostate cancer [5]. Several European countries have also withdrawn approval for bicalutamide for this indication.}}</ref> In addition, the {{abbr|U.S.|United States}} and Canada explicitly recommended against the use of 150&nbsp;mg/day bicalutamide for this indication.<ref name="NargundRaghavan2015">{{cite book | vauthors = Nargund VH, Raghavan D, Sandler HM |title=Urological Oncology |url=https://books.google.com/books?id=WmgzBgAAQBAJ&pg=PA823 |date=17 January 2015 |publisher=Springer |isbn=978-0-85729-482-1 |pages=823–|quote=On the other hand, the 150 mg dose of bicalutamide has been associated with some safety concerns, such as a higher death rate when added to active surveillance in the early prostate cancer trialists group study [29], which has led the United States and Canada to recommend against prescribing the 150 mg dose [30].}}</ref> The drug is effective for, remains approved for, and continues to be used in the treatment of {{abbr|LAPC|locally advanced prostate cancer}} and {{abbr|mPC|metastatic prostate cancer}}, on the other hand.<ref name="Wellington2006" />

The patent protection of bicalutamide expired in the {{abbr|U.S.|United States}} in March 2009 and the drug has subsequently been available as a generic,<ref name="Moul2009">{{cite journal |vauthors=Moul JW |title=Twenty years of controversy surrounding combined androgen blockade for advanced prostate cancer |journal=Cancer |volume=115 |issue=15 |pages=3376–8 |date=August 2009 |pmid=19484788 |doi=10.1002/cncr.24393|s2cid=5670663 |doi-access=free }}</ref> at greatly reduced cost.<ref name="Kampel2012">{{cite book |vauthors=Kampel LJ |title=Dx/Rx: Prostate Cancer |url=https://books.google.com/books?id=ueWH2bOXmEQC&pg=PA178 |date=20 March 2012 |publisher=Jones & Bartlett Publishers |isbn=978-0-7637-9453-8 |pages=178– |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143144/https://books.google.com/books?id=ueWH2bOXmEQC&pg=PA178 |url-status=live }}</ref>

Bicalutamide was the fourth antiandrogen (and the third {{abbr|NSAA|nonsteroidal antiandrogen}}) to be introduced for the treatment of prostate cancer, following the {{abbr|SAA|steroidal antiandrogen}} {{abbr|CPA|cyproterone acetate}} in 1973<ref name="TobiasHochhauser2014">{{cite book | vauthors = Tobias JS, Hochhauser D |title=Cancer and its Management |url=https://books.google.com/books?id=CXjDBAAAQBAJ&pg=PA379 |date=3 October 2014 |publisher=Wiley |isbn=978-1-118-46871-5 |pages=379–}}</ref> and the {{abbr|NSAAs|nonsteroidal antiandrogens}} flutamide in 1983 (1989 in the {{abbr|U.S.|United States}})<ref name="Publishing2013" /><ref name="Neal1994">{{cite book | vauthors = Neal DE |title=Tumours in Urology |url=https://books.google.com/books?id=k28yBwAAQBAJ&pg=PT233 |year=1994 |publisher=Springer Science & Business Media |isbn=978-1-4471-2086-5 |pages=233–|url-status=live |archive-url=https://web.archive.org/web/20160427062731/https://books.google.com/books?id=k28yBwAAQBAJ&pg=PT233 |archive-date=27 April 2016 |df=dmy-all}}</ref> and nilutamide in 1989 (1996 in the {{abbr|U.S.|United States}}).<ref name="BéguéBonnet-Delpon2008" /><ref name="Regitz-Zagrosek2012">{{cite book | vauthors = Regitz-Zagrosek V |title=Sex and Gender Differences in Pharmacology |url=https://books.google.com/books?id=J3VxihGDh9wC&pg=PA575 |date=2 October 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-30725-6 |pages=575–|url-status=live |archive-url=https://web.archive.org/web/20160624054637/https://books.google.com/books?id=J3VxihGDh9wC&pg=PA575 |archive-date=24 June 2016 |df=dmy-all}}</ref><ref name="pmid15833816">{{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=6201–6 |date=April 2005 |pmid=15833816 |pmc=1087923 |doi=10.1073/pnas.0500381102|bibcode=2005PNAS..102.6201B |doi-access=free }}</ref> It has been followed by [[abiraterone acetate]] in 2011, enzalutamide in 2012, apalutamide in 2018, and darolutamide in 2019, and may also be followed by in-development drugs such as [[proxalutamide]] and [[seviteronel]].<ref name="pmid26585581">{{cite journal |vauthors=Kolinsky M, de Bono JS |title=The Ongoing Challenges of Targeting the Androgen Receptor |journal=European Urology |volume=69 |issue=5 |pages=841–3 |year=2016 |pmid=26585581 |doi=10.1016/j.eururo.2015.10.052 |url=http://www.europeanurology.com/article/S0302-2838(15)01086-6/pdf/the-ongoing-challenges-of-targeting-the-androgen-receptor |access-date=9 September 2016 |archive-date=20 September 2016 |archive-url=https://web.archive.org/web/20160920030740/http://www.europeanurology.com/article/S0302-2838(15)01086-6/pdf/the-ongoing-challenges-of-targeting-the-androgen-receptor |url-status=live |url-access=subscription }}</ref>

==Society and culture==

===Generic names===
''Bicalutamide'' is the [[generic term|generic name]] of the drug in English and French and its {{abbrlink|INN|International Nonproprietary Name|INN}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}},<ref name="KEGG">{{cite encyclopedia |url=http://www.kegg.jp/entry/D00961 |title=Bicalutamide |encyclopedia=Kyoto Encyclopedia of Genes and Genomes (KEGG) |url-status=live |archive-url=https://web.archive.org/web/20161126002030/http://www.kegg.jp/entry/D00961 |archive-date=26 November 2016 |df=dmy-all}}</ref> {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, {{abbrlink|AAN|Australian Approved Name}},<ref name="TGALabel" /> and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Drugs.com-2" /><ref name="MortonHall2012">{{cite book | vauthors = Morton IK, Hal JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms |url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA51 |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-94-011-4439-1 |pages=51–|url-status=live |archive-url=https://web.archive.org/web/20160514090313/https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA51 |archive-date=14 May 2016 |df=dmy-all}}</ref><ref name="IndexNominum2000" /><ref name="GanellinTriggle1996">{{cite book | vauthors = Ganellin CR, Triggle DJ |title=Dictionary of Pharmacological Agents |url=https://books.google.com/books?id=Z_mfTTIApVEC&pg=PA570 |date=21 November 1996 |publisher=CRC Press |isbn=978-0-412-46630-4 |pages=570–|url-status=live |archive-url=https://web.archive.org/web/20160507003409/https://books.google.com/books?id=Z_mfTTIApVEC&pg=PA570 |archive-date=7 May 2016 |df=dmy-all}}</ref> It is also referred to as ''bicalutamidum'' in [[Latin]], ''bicalutamida'' in Spanish and [[Portuguese language|Portuguese]], ''bicalutamid'' in German, and ''bikalutamid'' in Russian and other [[Slavic languages]].<ref name="Drugs.com-2" /><ref name="IndexNominum2000" /> The "bica-" prefix corresponds to the fact that bicalutamide is a [[bicyclic compound|''bicyclic'' compound]],{{Citation needed|reason=Sources provided only explain -lutamide|date=October 2025}} while the "-lutamide" suffix is the standard suffix for {{abbr|NSAAs|nonsteroidal antiandrogens}}.<ref name="WHO2013">{{cite report |url=https://www.who.int/medicines/services/inn/StemBook_2013_Final.pdf |title=The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances |publisher=World Health Organisation |year=2013 |number=WHO/EMP/RHT/TSN/2013.1 |access-date=2020-06-06 |archive-date=9 August 2017 |archive-url=https://web.archive.org/web/20170809174219/http://www.who.int/medicines/services/inn/StemBook_2013_Final.pdf |url-status=dead }}</ref><ref name="NLM-DrugPortal">{{cite web |url=https://druginfo.nlm.nih.gov/drugportal/name/endswith/lutamide |website=Drug Information Portal |title=21 results for Name/Synonym ends with LUTAMIDE |access-date=19 November 2017 |archive-date=27 July 2020 |archive-url=https://web.archive.org/web/20200727011709/https://druginfo.nlm.nih.gov/drugportal/name/endswith/lutamide |url-status=dead }}</ref> Bicalutamide is also known by its former [[Code name#Project code name|developmental code name]] {{abbr|ICI|Imperial Chemical Industries}}-176,334.<ref name="MortonHall2012" /><ref name="IndexNominum2000" /><ref name="Drugs.com-2" />

===Brand names===
Bicalutamide is marketed by AstraZeneca in oral tablet form under the brand names Casodex, Cosudex, Calutide, Calumid, and Kalumid in many countries.<ref name="Drugs.com-2" /><ref name="IndexNominum2000" /><ref name="HuangJo2009">{{cite book |veditors=Huang D, Jo K, Lee H, Kang H, Bevilacqua V |title=Emerging Intelligent Computing Technology and Applications: 5th International Conference on Intelligent Computing, ICIC 2009 Ulsan, South Korea, September 16–19, 2009 Proceedings |chapter-url=https://books.google.com/books?id=gRFtCQAAQBAJ&pg=PA120 |date=19 September 2009 |publisher=Springer |isbn=978-3-642-04070-2 |pages=120– |chapter=Parallel Genetic Algorithms for Crystal Structure Prediction: Successes and Failures in Predicting Bicalutamide Polymorphs |vauthors=Ferraro MB, Orendt AM, Facelli JC |series=Lecture Notes in Computer Science |volume=5754 |doi=10.1007/978-3-642-04070-2_14 |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143147/https://books.google.com/books?id=gRFtCQAAQBAJ&pg=PA120 |url-status=live }}</ref><ref name="DhasIge2015">{{cite journal | vauthors = Dhas NL, Ige PP, Kudarha RR |title=Design, optimization and in-vitro study of folic acid conjugated-chitosan functionalized PLGA nanoparticle for delivery of bicalutamide in prostate cancer |journal=Powder Technology |volume=283 |year=2015 |pages=234–245 |doi=10.1016/j.powtec.2015.04.053}}</ref> It is also marketed under the brand names Bicadex, Bical, Bicalox, Bicamide, Bicatlon, Bicusan, Binabic, Bypro, Calutol, and Ormandyl among others in various countries.<ref name="Drugs.com-2" /> The drug is sold under a large number of generic trade names such as Apo-Bicalutamide, Bicalutamide Accord, Bicalutamide Actavis, Bicalutamide Bluefish, Bicalutamide Kabi, Bicalutamide Sandoz, and Bicalutamide Teva as well.<ref name="Drugs.com-2" /> A combination formulation of bicalutamide and goserelin is marketed by AstraZeneca in Australia and New Zealand under the brand name ZolaCos-CP.<ref name="Martindale2011" /><ref name="Drugs.com-3" /><ref name="ZolacosCPLabelAu" /><ref name="ZolacosCPLabelNZ" />

===Cost and generics===
Bicalutamide is off-patent and available as a generic.<ref name="Moul2009"/> Unlike bicalutamide, the newer {{abbr|NSAA|nonsteroidal antiandrogen}} enzalutamide is still [[chemical patent|on-patent]], and for this reason, is considerably more expensive in comparison.<ref name="RamadanKabbara2015">{{cite journal |vauthors=Ramadan WH, Kabbara WK, Al Basiouni Al Masri HS |title=Enzalutamide for patients with metastatic castration-resistant prostate cancer |journal=OncoTargets and Therapy |volume=8 |pages=871–6 |year=2015 |pmid=25945058 |doi=10.2147/OTT.S80488 |pmc=4407758 |doi-access=free }}</ref>

The [[patent protection]] of all three of the first-generation {{abbr|NSAAs|nonsteroidal antiandrogens}} has expired and flutamide and bicalutamide are both available as low-cost [[generic drug|generics]].<ref name="Stuhan2013">{{cite book |vauthors=Stuhan MA |title=Understanding Pharmacology for Pharmacy Technicians |url=https://books.google.com/books?id=L902nod-xOIC&pg=PT268 |date=2 April 2013 |publisher=ASHP |isbn=978-1-58528-360-6 |pages=268– |access-date=5 November 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143147/https://books.google.com/books?id=L902nod-xOIC&pg=PT268 |url-status=live }}</ref><ref name="pmid16604181">{{cite journal |vauthors=Allan GF, Sui Z |title=Therapeutic androgen receptor ligands |journal=Nucl Recept Signal |volume=1 |pages=e009 |year=2003 |pmid=16604181 |pmc=1402218 |doi=10.1621/nrs.01009 }}</ref> Nilutamide, on the other hand, has always been a poor third competitor to flutamide and bicalutamide and, in relation to this fact, has not been developed as a generic and is only available as brand name Nilandron, at least in the {{abbr|U.S.|United States}}<ref name="Stuhan2013" /><ref name="pmid16604181" />

Bicalutamide is considerably less costly than {{abbr|GnRH|gonadotropin-releasing hormone}} analogues, which, in spite of some having been off-patent many years, have been reported (in 2013) to typically cost {{currency|10,000|USD|linked=no}}–$15,000 per year (or about {{currency|1,000|USD|linked=no}} per month) of treatment.<ref name="EmansLaufer2012">{{cite book | vauthors = Emans SJ, Laufer MR |title=Emans, Laufer, Goldstein's Pediatric and Adolescent Gynecology |url=https://books.google.com/books?id=pdNh7ieMJzQC&pg=PT365 |date=5 January 2012 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-5406-1 |pages=365–|quote=Therapy with GnRH analogs is expensive and requires intramuscular injections of depot formulations, the insert of a subcutaneous implant yearly, or, much less commonly, daily subcutaneous injections. |url-status=live |archive-url=https://web.archive.org/web/20160516152443/https://books.google.com/books?id=pdNh7ieMJzQC |archive-date=16 May 2016 |df=dmy-all}}</ref><ref name="Hillard2013">{{cite book |vauthors=Hillard PJ |title=Practical Pediatric and Adolescent Gynecology |url=https://books.google.com/books?id=vAA5Z5aqlUQC&pg=PT182 |date=29 March 2013 |publisher=John Wiley & Sons |isbn=978-1-118-53857-9 |pages=182– |quote=Treatment is expensive, with costs typicall in the range of $10,000–$15,000 per year. |access-date=27 September 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114143147/https://books.google.com/books?id=vAA5Z5aqlUQC&pg=PT182 |url-status=live }}</ref>

===Sales and usage===
Sales of bicalutamide (as Casodex) worldwide peaked at [[United States dollar|US$]]1.3&nbsp;billion in 2007,<ref name="AstraZeneca2007" /> and it has been described as a "billion-dollar-a-year" drug prior to losing its patent protection starting in 2007.<ref name="Campbell2014" /><ref name="Evaluate2008" /><ref name="pmid16821162">{{cite journal |vauthors=Hermkens PH, Kamp S, Lusher S, Veeneman GH |title=Non-steroidal steroid receptor modulators |journal=IDrugs |volume=9 |issue=7 |pages=488–94 |date=July 2006 |pmid=16821162 |doi=10.2174/0929867053764671}}</ref> In 2014, despite the introduction of abiraterone acetate in 2011 and enzalutamide in 2012, bicalutamide was still the most commonly prescribed drug in the treatment of [[Prostate cancer#Castration-resistant|metastatic castration-resistant prostate cancer]] (mCRPC).<ref name="Campbell2014" /> Moreover, in spite of being off-patent, bicalutamide was said to still generate a few hundred million dollars in sales per year for AstraZeneca.<ref name="Campbell2014" /> Total worldwide sales of brand name Casodex were approximately [[United States dollar|US$]]13.4&nbsp;billion as of the end of 2018.<ref name="NewMedicine1996" /><ref name="NewYorkTimes1997" /><ref name="AstraZeneca1999" /><ref name="AstraZeneca2001" /><ref name="AstraZeneca2004" /><ref name="AstraZeneca2007" /><ref name="AstraZeneca2010" /><ref name="AstraZeneca2013" /><ref name="AstraZeneca2016" /><ref name="AstraZeneca2017" /><ref name="AstraZeneca2018" />{{citation overkill|date=May 2021}}

{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;"
|+ class="nowrap" | Worldwide sales (millions, {{abbr|USD|United States dollar}}) of Casodex, 1995–2018
|-
! Year !! Sales !! Year !! Sales !! Year !! Sales !! Year !! Sales !! Year !! Sales !! Year !! Sales !! Year !! Sales !! Year !! Sales
|-
| 1995 || ~$15m || 1998 || $245m || 2001 || $569m || 2004 || $1012m || 2007'''*''' || $1335m || 2010 || $579m || 2013 || $376m || 2016 || $247m
|-
| 1996 || $109m || 1999 || $340m || 2002 || $644m || 2005 || $1123m || 2008 || $1258m || 2011 || $550m || 2014 || $320m || 2017 || $215m
|-
| 1997 || $200m || 2000 || $433m || 2003 || $854m || 2006 || $1206m || 2009 || $844m || 2012 || $454m || 2015 || $267m || 2018 || $201m
|- class="sortbottom"
| colspan="16" style="background-color:#eaecf0; text-align: center;" | '''Notes:''' First [[generic drug|generic]] availability (*) was in 2007.<ref name="Evaluate2008">{{cite web |url=http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=159824 |title=Actavis Generic Prostate Cancer Drug Bicalutamide First to Market in UK, Germany, France |work=Press Release |publisher=AstraZeneca, Actavis |date=10 July 2008 |access-date=1 July 2017 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828003314/https://www.evaluate.com/ |url-status=dead }}</ref> Total sales as of end 2018 were $13.4 billion. '''Sources:'''<ref name="NewMedicine1996">{{cite journal |journal=Future Oncology |title=Hormonal Therapies |pages=306 |date=June 1996 |volume=2 |issue=2–3 |url=http://www.newmedinc.com/pdfs/Future_Oncology.Vol.2.No.2.3.pdf |access-date=1 July 2017 |archive-date=9 September 2017 |archive-url=https://web.archive.org/web/20170909052750/http://www.newmedinc.com/pdfs/Future_Oncology.Vol.2.No.2.3.pdf |url-status=dead }}</ref><!-- 1995 --><ref name="NewYorkTimes1997">{{cite web |url=https://www.nytimes.com/1997/03/12/business/zeneca-of-britain-posts-strong-drug-profits.html |title=Zeneca of Britain Posts Strong Drug Profits |work=The New York Times |date=12 March 1997}}</ref><!-- 1996 --><ref name="AstraZeneca1999" /><!-- 1997–1998 --><ref name="AstraZeneca2001">{{cite web |url=https://ddd.uab.cat/pub/infanu/40172/iaASTZENa2001ieng.pdf |title=Annual Report and Form 20-F 2001 |publisher=AstraZeneca}}</ref><!-- 1999–2001 --><ref name="AstraZeneca2004">{{cite web |url=https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-reports-homepage/2004-Annual-Report-English.pdf |title=Annual Report and Form 20-F 2004 |publisher=AstraZeneca}}</ref><!-- 2002–2004 --><ref name="AstraZeneca2007">{{cite web |url=https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-reports-homepage/2007-Annual-Report-English.pdf |title=Annual Report and Form 20-F 2007 |publisher=AstraZeneca}}</ref><!-- 2005–2007 --><ref name="AstraZeneca2010">{{cite web |url=https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-reports-homepage/2010-Annual-Report-English.pdf |title=Annual Report and Form 20-F 2010 |publisher=AstraZeneca}}</ref><!-- 2008–2010 --><ref name="AstraZeneca2013">{{cite web |url=https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-reports-homepage/2013-Annual-report-English.pdf |title=Annual Report and Form 20-F 2013 |publisher=AstraZeneca}}</ref><!-- 2011–2013 --><ref name="AstraZeneca2016">{{cite web |url=https://www.astrazeneca.com/content/dam/az/Investor_Relations/Annual-report-2016/AZ_AR2016_Full_Report.pdf |title=Annual Report and Form 20-F 2016 |publisher=AstraZeneca |url-status=live |archive-url=https://web.archive.org/web/20170403111027/https://www.astrazeneca.com/content/dam/az/Investor_Relations/Annual-report-2016/AZ_AR2016_Full_Report.pdf |archive-date=3 April 2017 |df=dmy-all}}</ref><!-- 2014–2016 --><ref name="AstraZeneca2017">{{cite web | url = https://www.astrazeneca.com/content/dam/az/PDF/2017/Full-Year/Full-Year%202017%20Results%20announcement%20.pdf | title = AstraZeneca Full-Year 2017 Results | publisher = AstraZeneca}}</ref><!-- 2017 --><ref name="AstraZeneca2018">{{cite web | url = https://www.astrazeneca.com/content/dam/az/PDF/2018/full-year/Full-Year_2018_Results_announcement.pdf | title = AstraZeneca Full-Year 2018 Results | publisher = AstraZeneca}}</ref><!-- 2018 -->
|}

Between January 2007 and December 2009 (a period of three years), 1,232,143 prescriptions of bicalutamide were dispensed in the {{abbr|U.S.|United States}}, or about 400,000 prescriptions per year.<ref name="HHS2010" /> During that time, bicalutamide accounted for about 87.2% of the {{abbr|NSAA|nonsteroidal antiandrogen}} market, while flutamide accounted for 10.5% of it and nilutamide for 2.3% of it.<ref name="HHS2010" /> Approximately 96% of bicalutamide prescriptions were written for diagnosis codes that clearly indicated [[neoplasm]].<ref name="HHS2010" /> About 1,200, or 0.1% of bicalutamide prescriptions were dispensed to pediatric patients (age 0–16).<ref name="HHS2010" />

===Regulation===
Bicalutamide is a [[prescription drug]].<ref name="MortonHall2001" /> It is not specifically a [[controlled substance]] in any country and therefore is not an [[illegal drug]].<ref name="AHFS2016" /> However, the [[pharmaceutical manufacturing|manufacture]], [[legal drug trade|sale]], [[drug distribution|distribution]], and [[drug possession|possession]] of prescription drugs are all still subject to [[regulation of therapeutic goods|legal regulation]] throughout the world.<ref name="YagielaDowd2010">{{cite book | vauthors = Yagiela JA, Dowd FJ, Johnson B, Mariotti A, Neidle EA |title=Pharmacology and Therapeutics for Dentistry |url=https://books.google.com/books?id=utVOHYuhxioC&pg=PA851 |date=19 March 2010 |publisher=Elsevier Health Sciences |isbn=978-0-323-07824-5 |pages=851–}}</ref><ref name="HeplerSegal2003">{{cite book | vauthors = Hepler CD, Segal R |title=Preventing Medication Errors and Improving Drug Therapy Outcomes: A Management Systems Approach |url=https://books.google.com/books?id=pvpZeDkaaIEC&pg=PA136 |date=25 February 2003 |publisher=CRC Press |isbn=978-0-203-01073-0 |pages=136–137}}</ref><ref name="DukesDukes1998">{{cite book | vauthors = Dukes G, Dukes MN, Mildred M, Swartz B |title=Responsibility for Drug-induced Injury: A Reference Book for Lawyers, the Health Professions and Manufacturers |url=https://books.google.com/books?id=EQ3CZ1NaoQgC&pg=PA241 |date=January 1998 |publisher=IOS Press |isbn=978-90-5199-387-5 |pages=241–8}}</ref>

==Research==
Bicalutamide has been studied in combination with the [[5α-reductase inhibitor]]s [[finasteride]] and [[dutasteride]] in prostate cancer.<ref name="pmid15138573">{{cite journal |vauthors=Wang LG, Mencher SK, McCarron JP, Ferrari AC |title=The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review |journal=Oncology Reports |volume=11 |issue=6 |pages=1325–9 |year=2004 |pmid=15138573 |doi= 10.3892/or.11.6.1325 }}</ref><ref name="pmid15151957">{{cite journal |vauthors=Tay MH, Kaufman DS, Regan MM, Leibowitz SB, George DJ, Febbo PG, Manola J, Smith MR, Kaplan ID, Kantoff PW, Oh WK |title=Finasteride and bicalutamide as primary hormonal therapy in patients with advanced adenocarcinoma of the prostate |journal=Annals of Oncology |volume=15 |issue=6 |pages=974–8 |year=2004 |pmid=15151957 |doi=10.1093/annonc/mdh221 |doi-access=free }}</ref><ref name="pmid16844453">{{cite journal |vauthors=Merrick GS, Butler WM, Wallner KE, Galbreath RW, Allen ZA, Kurko B |title=Efficacy of neoadjuvant bicalutamide and dutasteride as a cytoreductive regimen before prostate brachytherapy |journal=Urology |volume=68 |issue=1 |pages=116–20 |year=2006 |pmid=16844453 |doi=10.1016/j.urology.2006.01.061 }}</ref><ref name="pmid19796455">{{cite journal |vauthors=Sartor O, Gomella LG, Gagnier P, Melich K, Dann R |title=Dutasteride and bicalutamide in patients with hormone-refractory prostate cancer: the Therapy Assessed by Rising PSA (TARP) study rationale and design |journal=The Canadian Journal of Urology |volume=16 |issue=5 |pages=4806–12 |year=2009 |pmid=19796455 }}</ref><ref name="pmid26048455">{{cite journal |vauthors=Chu FM, Sartor O, Gomella L, Rudo T, Somerville MC, Hereghty B, Manyak MJ |title=A randomised, double-blind study comparing the addition of bicalutamide with or without dutasteride to GnRH analogue therapy in men with non-metastatic castrate-resistant prostate cancer |journal=European Journal of Cancer |volume=51 |issue=12 |pages=1555–69 |year=2015 |pmid=26048455 |doi=10.1016/j.ejca.2015.04.028 }}</ref><ref name="pmid26702991">{{cite journal |vauthors=Gaudet M, Vigneault É, Foster W, Meyer F, Martin AG |title=Randomized non-inferiority trial of Bicalutamide and Dutasteride versus LHRH agonists for prostate volume reduction prior to I-125 permanent implant brachytherapy for prostate cancer |journal=Radiotherapy and Oncology |volume=118 |issue=1 |pages=141–7 |year=2016 |pmid=26702991 |doi=10.1016/j.radonc.2015.11.022 }}</ref><ref name="pmid27330919">{{cite journal |vauthors=Dijkstra S, Witjes WP, Roos EP, Vijverberg PL, Geboers AD, Bruins JL, Smits GA, Vergunst H, Mulders PF |title=The AVOCAT study: Bicalutamide monotherapy versus combined bicalutamide plus dutasteride therapy for patients with locally advanced or metastatic carcinoma of the prostate-a long-term follow-up comparison and quality of life analysis |journal=SpringerPlus |volume=5 |article-number=653 |year=2016 |pmid=27330919 |pmc=4870485 |doi=10.1186/s40064-016-2280-8 |doi-access=free }}</ref> It has also been studied in combination with [[raloxifene]], a [[selective estrogen receptor modulator]] (SERM), for the treatment of prostate cancer.<ref name="FujimuraTakayama2018">{{cite journal | vauthors = Fujimura T, Takayama K, Takahashi S, Inoue S | title = Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine | journal = Cancers | volume = 10 | issue = 2 | pages = 29 | date = January 2018 | pmid = 29360794 | pmc = 5836061 | doi = 10.3390/cancers10020029 | doi-access = free }}</ref><ref name="HoNunez-Nateras2017">{{cite journal | vauthors = Ho TH, Nunez-Nateras R, Hou YX, Bryce AH, Northfelt DW, Dueck AC, Wong B, Stanton ML, Joseph RW, Castle EP | title = A Study of Combination Bicalutamide and Raloxifene for Patients With Castration-Resistant Prostate Cancer | journal = Clinical Genitourinary Cancer | volume = 15 | issue = 2 | pages = 196–202.e1 | date = April 2017 | pmid = 27771244 | doi = 10.1016/j.clgc.2016.08.026 | s2cid = 19043552 }}</ref> Bicalutamide has been tested for the treatment of {{abbr|AR|androgen receptor}}-positive {{abbr|ER|estrogen receptor}}/{{abbr|PR|progesterone receptor}}-negative locally advanced and [[metastatic breast cancer]] in women in a phase II study for this indication.<ref>{{cite journal |url=http://meetinglibrary.asco.org/content/94715-114 |title=Targeting the androgen receptor (AR) in women with AR+ ER-/PR- metastatic breast cancer (MBC) |journal=J Clin Oncol |year=2012 |issue=suppl |page=abstract 1006 |author=Translational Breast Cancer Research Consortium (TBCRC) |url-status=live |archive-url=https://web.archive.org/web/20150710035954/http://meetinglibrary.asco.org/content/94715-114 |archive-date=10 July 2015 |df=dmy-all}}</ref><ref>{{ClinicalTrialsGov|NCT00468715|Bicalutamide in Treating Patients With Metastatic Breast Cancer}}</ref><ref>{{cite journal |vauthors=Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA |title=Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer |journal=Clinical Cancer Research |volume=19 |issue=19 |pages=5505–12 |date=October 2013 |pmid=23965901 |pmc=4086643 |doi=10.1158/1078-0432.CCR-12-3327 | collaboration = Translational Breast Cancer Research Consortium (TBCRC 011)}}</ref> Enzalutamide is also being investigated for this type of cancer.<ref name="CaiazzaMurray2016">{{cite journal |vauthors=Caiazza F, Murray A, Madden SF, Synnott NC, Ryan EJ, O'Donovan N, Crown J, Duffy MJ |title=Preclinical evaluation of the AR inhibitor enzalutamide in triple-negative breast cancer cells |journal=Endocrine-Related Cancer |volume=23 |issue=4 |pages=323–34 |date=April 2016 |pmid=26932782 |doi=10.1530/ERC-16-0068|doi-access=free }}</ref><ref>{{cite journal |vauthors=Traina TA, etal |title=Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC). |journal=Journal of Clinical Oncology |volume=33 |date=2015 |issue=suppl |page=abstr 1003 |doi=10.1200/jco.2015.33.15_suppl.1003 |url=http://meetinglibrary.asco.org/content/150040-156 |url-status=live |archive-url=https://web.archive.org/web/20160530074130/http://meetinglibrary.asco.org/content/150040-156 |archive-date=30 May 2016 |df=dmy-all|url-access=subscription }}</ref> Bicalutamide has also been studied in a phase II clinical trial for [[ovarian cancer]] in women.<ref name="pmid17918264">{{cite journal |vauthors=Levine D, Park K, Juretzka M, Esch J, Hensley M, Aghajanian C, Lewin S, Konner J, Derosa F, Spriggs D, Iasonos A, Sabbatini P |title=A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission |journal=Cancer |volume=110 |issue=11 |pages=2448–56 |date=December 2007 |pmid=17918264 |doi=10.1002/cncr.23072|s2cid=21161915 |doi-access=free }}</ref>

Bicalutamide has been studied in the treatment of [[benign prostatic hyperplasia]] (BPH) in a 24-week trial of 15 patients at a dosage of 50&nbsp;mg/day.<ref name="Becker2001-2">{{cite book | vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism |url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1209 |year=2001 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-1750-2 |page=1209 |url-status=live |archive-url=https://web.archive.org/web/20140628110255/http://books.google.com/books?id=FVfzRvaucq8C |archive-date=28 June 2014 |df=dmy-all}}</ref><ref name="pmid7694413">{{cite journal |vauthors=Lepor H |title=Medical therapy for benign prostatic hyperplasia |journal=Urology |volume=42 |issue=5 |pages=483–501 |year=1993 |pmid=7694413 |doi=10.1016/0090-4295(93)90258-c |quote=The clinically significant adverse events reported in the casodex group included breast tenderness (93%), breast enlargement (54%), and sexual dysfunction (60%). In none of the patients in the placebo group did any of these adverse events develop. None of the subjects discontinued therapy owing to an adverse event.}}</ref> Prostate volume decreased by 26% in patients taking bicalutamide and [[dysuria|urinary irritative]] symptom scores significantly decreased.<ref name="Becker2001-2" /><ref name="pmid7694413" /> Conversely, peak [[urine flow rate]]s and [[urodynamic testing|urine pressure flow]] examinations were not significantly different between bicalutamide and placebo.<ref name="Becker2001-2" /><ref name="pmid7694413" /> The decrease in prostate volume achieved with bicalutamide was comparable to that observed with the 5α-reductase inhibitor [[finasteride]], which is approved for the treatment of BPH.<ref name="pmid9101011">{{cite journal |vauthors=Lee M, Sharifi R |title=Benign prostatic hyperplasia: diagnosis and treatment guideline |journal=Ann Pharmacother |volume=31 |issue=4 |pages=481–6 |year=1997 |pmid=9101011 |doi=10.1177/106002809703100415 |s2cid=20498549 }}</ref><ref name="pmid9135028">{{cite journal |vauthors=Kenny B, Ballard S, Blagg J, Fox D |title=Pharmacological options in the treatment of benign prostatic hyperplasia |journal=J. Med. Chem. |volume=40 |issue=9 |pages=1293–315 |year=1997 |pmid=9135028 |doi=10.1021/jm960697s }}</ref> Breast tenderness (93%), gynecomastia (54%), and sexual dysfunction (60%) were all reported as side effects of bicalutamide at the dosage used in the study, although no treatment discontinuations due to adverse effects occurred and sexual functioning was maintained in 75% of patients.<ref name="pmid7694413" /><ref name="Kolvenbag1996" />

A [[Phases of clinical research#Phase III|phase III]] clinical trial of bicalutamide in combination with an [[ethinylestradiol]]-containing [[combined oral contraceptive]] for the treatment of severe hirsutism in women with {{abbr|PCOS|polycystic ovary syndrome}} was completed in [[Italy]] in 2017 under supervision of the Italian Agency for Drugs (AIFA).<ref name="pmid29211888">{{cite journal | vauthors = Moretti C, Guccione L, Di Giacinto P, Simonelli I, Exacoustos C, Toscano V, Motta C, De Leo V, Petraglia F, Lenzi A | title = Combined Oral Contraception and Bicalutamide in Polycystic Ovary Syndrome and Severe Hirsutism: A Double-Blind Randomized Controlled Trial | journal = J. Clin. Endocrinol. Metab. | volume = 103 | issue = 3 | pages = 824–838 | date = March 2018 | pmid = 29211888 | doi = 10.1210/jc.2017-01186 | doi-access = free }}</ref>

Antiandrogens have been suggested for treating [[COVID-19]] in men and as of May 2020 high-dose bicalutamide is in a phase II clinical trial for this purpose.<ref name="pmid32333494">{{cite journal | vauthors = McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Müller Ramos P, Washenik K, Andrade M, Herrera S, Goren A | title = Racial Variations in COVID-19 Deaths May Be Due to Androgen Receptor Genetic Variants Associated with Prostate Cancer and Androgenetic Alopecia. Are Anti-Androgens a Potential Treatment for COVID-19? | journal = J Cosmet Dermatol | volume = 19| issue = 7| pages = 1542–1543| date = April 2020 | pmid = 32333494 | doi = 10.1111/jocd.13455 | doi-access = free | pmc = 7267367 }}</ref><ref name="NCT04374279">{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT04374279|title = A Phase II Trial to Promote Recovery from COVID-19 with Endocrine Therapy|date = 2 March 2021}}</ref>

==Veterinary use==
Bicalutamide may be used to treat hyperandrogenism and associated benign prostatic hyperplasia secondary to [[hyperadrenocorticism]] (caused by excessive adrenal androgens) in male [[ferret]]s.<ref name = "BonaguraTwedt2013">{{cite book | vauthors = Bonagura JD, Twedt DC |title=Kirk's Current Veterinary Therapy XV |url=https://books.google.com/books?id=KlJKAgAAQBAJ&pg=PT908 |date=1 December 2013 |publisher=Elsevier Health Sciences |isbn=978-0-323-22762-9 |page=908}}</ref><ref name = "MitchellTully2009">{{cite book | vauthors = Mitchell MA, Tully TN |title=Manual of Exotic Pet Practice |url=https://books.google.com/books?id=JMTUKwzPEvwC&pg=PA363 |year=2009 |publisher=Elsevier Health Sciences |isbn=978-1-4160-0119-5 |page=363}}</ref><ref name = "Pilny2014">{{cite book | vauthors = Pilny AA |title=Endocrinology, An Issue of Veterinary Clinics: Exotic Animal Practice |url=https://books.google.com/books?id=2MraAgAAQBAJ&pg=PA17 |date=9 February 2014 |publisher=Elsevier Health Sciences |isbn=978-0-323-26419-8 |pages=16–17 |quote=In ferrets, 5 mg/kg [of bicalutamide] orally every 24 hours has been used clinically, but no controlled toxicologic or pharmacologic studies have been published at this time.}}</ref> However, it has not been formally assessed in controlled studies for this purpose.<ref name = "Pilny2014" /><ref name = "FoxMarini2014">{{cite book | vauthors = Fox JG, Marini RP |title=Biology and Diseases of the Ferret |url=https://books.google.com/books?id=2J06AwAAQBAJ&pg=PT980 |date=26 March 2014 |publisher=Wiley |isbn=978-1-118-78273-6 |page=980 |quote=Other agents have been proposed for medical management of [adrenal-associated endocrinopathy] but have not been studied. Possibly medications include the androgen receptor blockers flutamide and bicalutamide, the anti-androgen finasteride, estrogen-inhibiting anastrozole, and another GnRH analog, goserelin. [...] None of these drugs have been tested in controlled clinical trials in ferrets.}}</ref>

==See also==
* [[Comparison of bicalutamide with other antiandrogens]]

==References==
{{Reflist|32em}}

==Further reading==
{{Refbegin|33em}}
* {{cite book | title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury | url=https://www.ncbi.nlm.nih.gov/books/NBK547852/ | chapter=Bicalutamide | via=NCBI Bookshelf | year=2017 | publisher=National Institute of Diabetes and Digestive and Kidney Diseases | pmid=31643303 | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK547970/ | id=NBK547970 }}
* {{cite journal |vauthors=Blackledge GR |title=Clinical progress with a new antiandrogen, Casodex (bicalutamide) |journal=European Urology |volume=29 | issue = Suppl 2 |pages=96–104 |year=1996 |pmid=8717470 |doi=10.1159/000473847}}
* {{cite journal |vauthors=Cockshott ID |title=Bicalutamide: clinical pharmacokinetics and metabolism |journal=Clinical Pharmacokinetics |volume=43 |issue=13 |pages=855–78 |year=2004 |pmid=15509184 |doi=10.2165/00003088-200443130-00003|s2cid=29912565 }}
* {{cite journal |vauthors=Fradet Y |title=Bicalutamide (Casodex) in the treatment of prostate cancer |journal=Expert Review of Anticancer Therapy |volume=4 |issue=1 |pages=37–48 |date=February 2004 |pmid=14748655 |doi=10.1586/14737140.4.1.37|s2cid=34153031 }}
* {{cite journal |vauthors=Furr BJ |title=Casodex: preclinical studies and controversies |journal=Annals of the New York Academy of Sciences |volume=761 |issue=1 |pages=79–96 |date=June 1995 |pmid=7625752 |doi=10.1111/j.1749-6632.1995.tb31371.x|bibcode=1995NYASA.761...79F |s2cid=37242269 }}
* {{cite journal |vauthors=Furr BJ, Tucker H |title=The preclinical development of bicalutamide: pharmacodynamics and mechanism of action |journal=Urology |volume=47 |issue=1A Suppl |pages=13–25; discussion 29–32 |date=January 1996 |pmid=8560673 |doi=10.1016/S0090-4295(96)80003-3}}
* {{cite journal |vauthors=Kolvenbag GJ, Blackledge GR |title=Worldwide activity and safety of bicalutamide: a summary review |journal=Urology |volume=47 |issue=1A Suppl |pages=70–9; discussion 80–4 |date=January 1996 |pmid=8560681 |doi=10.1016/s0090-4295(96)80012-4}}
* {{cite journal |vauthors=Schellhammer PF, Davis JW |title=An evaluation of bicalutamide in the treatment of prostate cancer |journal=Clinical Prostate Cancer |volume=2 |issue=4 |pages=213–9 |date=March 2004 |pmid=15072604 |doi=10.3816/CGC.2004.n.002}}
* {{cite journal |vauthors=Tucker H, Crook JW, Chesterson GJ |title=Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides |journal=J. Med. Chem. |volume=31 |issue=5 |pages=954–9 |year=1988 |pmid=3361581 |doi=10.1021/jm00400a011 }}
* {{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=837–50 |year=2006 |pmid=16706554 |doi=10.2165/00003495-200666060-00007|s2cid=46966712 }}
{{Refend}}

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