Flutamide

Flutamide
Clinical data
Trade namesEulexin, others
Other namesNiftolide; SCH-13521; 4'-Nitro-3'-trifluoromethyl-isobutyranilide
AHFS/Drugs.comMonograph
MedlinePlusa697045
Pregnancy
category
  • D
Routes of
administration		By mouth
Drug classNonsteroidal antiandrogen
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityComplete (>90%)[1]
Protein bindingFlutamide: 94–96%[1]
Hydroxyflutamide: 92–94%[1]
MetabolismLiver (CYP1A2)[7][3]
MetabolitesHydroxyflutamide[2][3]
Elimination half-lifeFlutamide: 5–6 hours[4][3]
Hydroxyflutamide: 8–10 hours[5][6][3][1]
ExcretionUrine (mainly)[1]
Feces (4.2%)[1]
Identifiers
IUPAC name
  • 2-Methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.033.024
Chemical and physical data
FormulaC11H11F3N2O3
Molar mass276.215 g·mol−1
3D model (JSmol)
Melting point111.5 to 112.5 °C (232.7 to 234.5 °F)
SMILES
  • CC(C)C(=O)NC1=CC(=C(C=C1)[N+](=O)[O-])C(F)(F)F
InChI
  • InChI=1S/C11H11F3N2O3/c1-6(2)10(17)15-7-3-4-9(16(18)19)8(5-7)11(12,13)14/h3-6H,1-2H3,(H,15,17) Y
  • Key:MKXKFYHWDHIYRV-UHFFFAOYSA-N Y
  (verify)

Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer.[8][9] It is also used in the treatment of androgen-dependent conditions like acne, excessive hair growth, and high androgen levels in women.[10] It is taken by mouth, usually three times per day.[11]

Side effects in men include breast tenderness and enlargement, feminization, sexual dysfunction, and hot flashes. Conversely, the medication has fewer side effects and is better-tolerated in women with the most common side effect being dry skin. Diarrhea and elevated liver enzymes can occur in both sexes. Rarely, flutamide can cause liver damage, lung disease, sensitivity to light, elevated methemoglobin, elevated sulfhemoglobin, and deficient neutrophils.[12][13][14][15] Numerous cases of liver failure and death have been reported, which has limited the use of flutamide.[12]

Flutamide acts as a selective antagonist of the androgen receptor (AR), competing with androgens like testosterone and dihydrotestosterone (DHT) for binding to ARs in tissues like the prostate gland. By doing so, it prevents their effects and stops them from stimulating prostate cancer cells to grow. Flutamide is a prodrug to a more active form. Flutamide and its active form stay in the body for a relatively short time, which makes it necessary to take flutamide multiple times per day.

Flutamide was first described in 1967 and was first introduced for medical use in 1983.[16] It became available in the United States in 1989. The medication has largely been replaced by newer and improved NSAAs, namely bicalutamide and enzalutamide, due to their better efficacy, tolerability, safety, and dosing frequency (once per day), and is now relatively little-used.[4][17] It is on the World Health Organization's List of Essential Medicines.[18]

  1. ^ a b c d e f "Flutamide Capsules USP".
  2. ^ Cite error: The named reference pmid10495361 was invoked but never defined (see the help page).
  3. ^ a b c d Cite error: The named reference ChabnerLongo2010 was invoked but never defined (see the help page).
  4. ^ a b Gulley JL (2011). Prostate Cancer. Demos Medical Publishing. pp. 81–. ISBN 978-1-935281-91-7.
  5. ^ Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1373–. ISBN 978-1-60913-345-0.
  6. ^ Cite error: The named reference DenisGriffiths1999 was invoked but never defined (see the help page).
  7. ^ Cite error: The named reference Lehne2013 was invoked but never defined (see the help page).
  8. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 466–. ISBN 978-3-88763-075-1.
  9. ^ Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 573–. ISBN 978-1-4757-2085-3.
  10. ^ "Polycystic Ovary Syndrome - Treatment - NHS Choices". Nhs.uk. 2011-10-17. Archived from the original on 2011-11-06. Retrieved 2013-01-04.
  11. ^ Mungadi IA, Shittu OB, Abdulwahab-Ahmed A (30 November 2013). "Prostate Cancer". In Mungadi IA, Mbibu HN, Eltahawy E, Abdulwahab-Ahmed A (eds.). Manual of Medical Treatment in Urology. JP Medical Ltd. pp. 120–. ISBN 978-93-5090-844-0.
  12. ^ a b Cite error: The named reference pmid28379593 was invoked but never defined (see the help page).
  13. ^ Cite error: The named reference pmid12353966 was invoked but never defined (see the help page).
  14. ^ Cite error: The named reference Aronson2010 was invoked but never defined (see the help page).
  15. ^ McLeod DG (1997). "Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer". The Oncologist. 2 (1): 18–27. doi:10.1634/theoncologist.2-1-18. PMID 10388026.
  16. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 515. ISBN 9783527607495.
  17. ^ Wirth MP, Hakenberg OW, Froehner M (1 January 2008). "Adjuvant Hormonal Treatment - The Bicalutamide Early Prostate Cancer Program". In Moser L (ed.). Controversies in the Treatment of Prostate Cancer. Karger Medical and Scientific Publishers. pp. 41–42. ISBN 978-3-8055-8524-8. Latest studies suggest that [flutamide] also reduces adrenal and ovarian androgen synthesis [58,59]. [...] No alteration in the hormone levels has been observed in patients treated with flutamide for 6 or 12 months [61,62]. However in other studies flutamide decreased circulating concentrations of DHEAS as well as androstenedione, total testosterone and 3a-androstanediol glucuronide, in young women with PCOS [41,59]. These effects may be due to inhibition of adrenal 17-20 lyase [17,63]. Although there was no effect on gonadotropin response to GnRH, basal levels of FSH showed a rise associated with a small fall of LH [64].
  18. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
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