Back بيكالوتاميد Arabic بیکالوتامید AZB بایکالوتاماید CKB Deucalwtamid Welsh Bicalutamid German Bicalutamida Spanish بیکالوتامید Persian Bikalutamidi Finnish Bicalutamide Italian ビカルタミド Japanese

Bicalutamide

Bicalutamide
Clinical data
PronunciationBicalutamide:
• /ˌbaɪkəˈluːtəmaɪd/[1]
• BY-kə-LOO-tə-myde[1]
Trade namesCasodex, Calutex, others
Other namesICI-176,334; ZD-176,334
AHFS/Drugs.comMonograph
MedlinePlusa697047
License data
Pregnancy
category
  • AU: D
Routes of
administration		By mouth[2]
Drug classNonsteroidal antiandrogen
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityWell-absorbed; absolute bioavailability unknown[3]
Protein bindingRacemate: 96.1%[2]
(R)-Isomer: 99.6%[2]
(Mainly to albumin)[2]
MetabolismLiver (extensively):[4][9]
• Hydroxylation (CYP3A4)
• Glucuronidation (UGT1A9)
Metabolites• Bicalutamide glucuronide
• Hydroxybicalutamide
• Hydroxybicalutamide gluc.
(All inactive)[4][2][5][6]
Elimination half-lifeSingle-dose: 5.8 days[7]
Continuous: 7–10 days[8]
ExcretionFeces: 43%[4]
Urine: 34%[4]
Identifiers
  • (RS)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.126.100 Edit this at Wikidata
Chemical and physical data
FormulaC18H14F4N2O4S
Molar mass430.37 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture (of (R)- and (S)-enantiomers)
Melting point191 to 193 °C (376 to 379 °F) (experimental)
Boiling point650 °C (1,202 °F) (predicted)
Solubility in water0.005
  • CC(O)(CS(=O)(=O)c1ccc(F)cc1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
  • InChI=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) checkY
  • Key:LKJPYSCBVHEWIU-UHFFFAOYSA-N checkY
  (verify)

Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer.[10] It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC).[11][10][12] To a lesser extent, it is used at high doses for locally advanced prostate cancer (LAPC) as a monotherapy without castration.[4][2][13] Bicalutamide was also previously used as monotherapy to treat localized prostate cancer (LPC), but authorization for this use was withdrawn following unfavorable trial findings.[13][14][15][16] Besides prostate cancer, bicalutamide is limitedly used in the treatment of excessive hair growth and scalp hair loss in women,[17][18] as a puberty blocker and component of feminizing hormone therapy for transgender girls and women,[19] to treat gonadotropin-independent early puberty in boys,[20] and to prevent overly long-lasting erections in men.[21] It is taken by mouth.[10]

Common side effects of bicalutamide in men include breast growth, breast tenderness, and hot flashes.[10] Other side effects in men include feminization and sexual dysfunction.[22][23] Some side effects like breast changes and feminization are minimal when combined with castration.[24] 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.[25][10] Use during pregnancy may harm the baby.[10] In men with early prostate cancer, bicalutamide monotherapy has been found to increase the likelihood of death from causes other than prostate cancer.[26][13] Bicalutamide produces abnormal liver changes necessitating discontinuation in around 1% of people.[27][13] Rarely, it has been associated with cases of serious liver damage,[10] serious lung toxicity,[3] and sensitivity to light.[28][29] Although the risk of adverse liver changes is small, monitoring of liver function is recommended during treatment.[10]

Bicalutamide is a member of the nonsteroidal antiandrogen (NSAA) group of medications.[3] It works by selectively blocking the androgen receptor (AR), the biological target of the androgen sex hormones testosterone and dihydrotestosterone (DHT).[30] It does not lower androgen levels.[3] The medication can have some estrogen-like effects in men when used as a monotherapy due to increased estradiol levels.[31][32][33] Bicalutamide is well-absorbed, and its absorption is not affected by food.[2] The elimination half-life of the medication is around one week.[2][10] It shows peripheral selectivity in animals, but crosses the blood–brain barrier and affects both the body and brain in humans.[2][34]

Bicalutamide was patented in 1982 and approved for medical use in 1995.[35] It is on the World Health Organization's List of Essential Medicines.[36] Bicalutamide is available as a generic medication.[37] The drug is sold in more than 80 countries, including most developed countries.[38][39][40] 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.[23][41][42][43][44] Although bicalutamide is also used for other indications besides prostate cancer, the vast majority of prescriptions appear to be for treatment of prostate cancer.[44]

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  3. ^ a b c d Dart RC (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 497, 521. ISBN 978-0-7817-2845-4. Archived from the original on 11 May 2016.
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  6. ^ Schellhammer PF (September 2002). "An evaluation of bicalutamide in the treatment of prostate cancer". Expert Opinion on Pharmacotherapy. 3 (9): 1313–28. doi:10.1517/14656566.3.9.1313. PMID 12186624. S2CID 32216411. The clearance of bicalutamide occurs pre- dominantly by hepatic metabolism and glucuronidation, with excretion of the resulting inactive metabolites in the urine and faces.
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  43. ^ Campbell T (22 January 2014). "Slowing Sales for Johnson & Johnson's Zytiga May Be Good News for Medivation". The Motley Fool. Archived from the original on 26 August 2016. Retrieved 20 July 2016. [...] 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, [...]
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