Nilutamide

Nilutamide

Nilutamide
Systematic (IUPAC) name
5,5-dimethyl-3-(4-nitro-3-(trifluoromethyl)phenyl)imidazolidine-2,4-dione
Clinical data
Trade names Nilandron
AHFS/Drugs.com
MedlinePlus
Legal status
  • (Prescription only)
Routes of
administration
Oral
Pharmacokinetic data
Biological half-life ~56 hours[1]
Identifiers
CAS Registry Number  Y
ATC code L02
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Synonyms RU-23908
Chemical data
Formula C12H10F3N3O4
Molecular mass 317.221 g/mol
 Y   

Nilutamide (synthetic, non-steroidal, pure antiandrogen used in the treatment of advanced-stage (metastatic) prostate cancer.[2][3][4] It was developed by Roussel, introduced in 1987,[2] and was the second non-steroidal antiandrogen to be marketed after flutamide.[4] Nilutamide acts as a potent and selective competitive silent antagonist of the androgen receptor (AR), which prevents testosterone and other androgens from activating the AR.[5] Because most prostate cancer cells rely on activation of the AR for growth and survival, nilutamide can extend life in men with prostate cancer.[5]

Nilutamide is used in prostate cancer in combination with a GnRH analogue at a dosage of 300 mg daily for the first 4 weeks of treatment, and 150 mg once daily thereafter.[6][1] It is not indicated as a monotherapy in prostate cancer.[1] Nilutamide has a half-life of approximately two days, which allows for once-daily administration.[4] In addition to prostate cancer, nilutamide has also been studied in and used as a component of hormone replacement therapy in trans women.[5][7]

General side effects of non-steroidal antiandrogens, including nilutamide, include gynecomastia, breast pain/tenderness, hot flashes, depression, fatigue, and sexual dysfunction.[8][9] In addition, relative to other non-steroidal antiandrogens, nilutamide has been uniquely associated with mild and reversible visual disturbances (31%), a disulfiram-like[8] alcohol intolerance (19%), and interstitial pneumonitis (1–2%[10][11]) (which can progress to pulmonary fibrosis[12]), and has a higher incidence of nausea (27%) and vomiting than other non-steroidal antiandrogens.[1][13][4] There is also a risk of hepatoxicity with nilutamide, though occurrence is very rare and the risk is significantly less than with flutamide.[14][15] The unique adverse effects of nilutamide, and especially its risk of interstitial pneumonitis, have limited its clinical use relative to other non-steroidal antiandrogens.[1][4] From a safety standpoint, bicalutamide is clinically preferred over both nilutamide (due to interstitial pneumonitis) and flutamide (due to hepatotoxicity) in regards to choice of non-steroidal antiandrogen.[11]

Like other non-steroidal antiandrogens such as flutamide and bicalutamide, nilutamide, without concomitant GnRH analogue therapy, increases serum androgen (by two-fold in the case of testosterone), estrogen, and prolactin levels due to inhibition of AR-mediated suppression of steroidogenesis via negative feedback on the hypothalamic-pituitary-gonadal axis.[5] As such, though nilutamide is still highly effective as an antiandrogen as a monotherapy, it is given in combination with a GnRH analogue such as leuprorelin in prostate cancer to suppress androgen concentrations to castrate levels in order to attain maximal androgen blockade (MAB).[5]

Like flutamide and bicalutamide, nilutamide is able to cross the blood-brain-barrier and has central antiandrogen actions.[16]

See also

References

  1. ^ a b c d e Chawnshang Chang (1 January 2005). Prostate Cancer: Basic Mechanisms and Therapeutic Approaches. World Scientific. pp. 11–.  
  2. ^ a b C.R. Ganellin; David J. Triggle (21 November 1996). Dictionary of Pharmacological Agents. CRC Press. pp. 1431–.  
  3. ^ Dr. Ian Morton; I.K. Morton; Judith M. Hall (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 199–.  
  4. ^ a b c d e Louis J Denis; Keith Griffiths; Amir V Kaisary; Gerald P Murphy (1 March 1999). Textbook of Prostate Cancer: Pathology, Diagnosis and Treatment: Pathology, Diagnosis and Treatment. CRC Press. pp. 280–.  
  5. ^ a b c d e Louis Denis (6 December 2012). Antiandrogens in Prostate Cancer: A Key to Tailored Endocrine Treatment. Springer Science & Business Media. pp. 194–210.  
  6. ^ Jonathan Upfal (2006). The Australian Drug Guide: Every Person's Guide to Prescription and Over-the-counter Medicines, Street Drugs, Vaccines, Vitamins and Minerals... Black Inc. pp. 283–.  
  7. ^ Baudewijntje P.C. Kreukels; Thomas D. Steensma; Annelou L.C. de Vries (1 July 2013). Gender Dysphoria and Disorders of Sex Development: Progress in Care and Knowledge. Springer Science & Business Media. pp. 280–.  
  8. ^ a b Richard C. Dart (2004). Medical Toxicology. Lippincott Williams & Wilkins. pp. 521–.  
  9. ^ Lisa M DeAngelis MD; Jerome B Posner MD (12 September 2008). Neurologic Complications of Cancer. Oxford University Press, USA. pp. 479–.  
  10. ^ Phillipe Camus; Edward C Rosenow III (29 October 2010). Drug-induced and Iatrogenic Respiratory Disease. CRC Press. pp. 235–.  
  11. ^ a b James Leonard Gulley (2011). Prostate Cancer. Demos Medical Publishing. pp. 81–.  
  12. ^ Alan J. Wein; Louis R. Kavoussi; Andrew C. Novick; Alan W. Partin, Craig A. Peters (25 August 2011). Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set. Elsevier Health Sciences. pp. 2939–.  
  13. ^ J. Ramon; L.J. Denis (5 June 2007). Prostate Cancer. Springer Science & Business Media. pp. 229–.  
  14. ^ Virgil Craig Jordan; B. J. A. Furr (5 February 2010). Hormone Therapy in Breast and Prostate Cancer. Springer Science & Business Media. pp. 356–.  
  15. ^ Jeffrey K. Aronson (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 150–.  
  16. ^ Raynaud, Jean-Pierre; Bonne, Claude; Bouton, Marie-Madeleine; Lagace, Lisette; Labrie, Fernand (1979). "Action of a non-steroid anti-androgen, RU 23908, in peripheral and central tissues". Journal of Steroid Biochemistry 11 (1): 93–99.