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Other names
  • Fexinidazole Winthrop
  • HOE 239
  • 1-Methyl-2-{[4-(methylsulfanyl)phenoxy]methyl}-5-nitro-1H-imidazole
Clinical data
Main usesAfrican trypanosomiasis (sleeping sickness) cause by Trypanosoma brucei gambiense[1]
Side effectsNausea, vomiting, headache, trouble sleeping[2]
Defined daily dose1.4 gram[3]
External links
Chemical and physical data
Molar mass279.31 g·mol−1
3D model (JSmol)
  • [O-][N+](=O)c1cnc(n1C)COc2ccc(SC)cc2

Fexinidazole is a medication used to treat African trypanosomiasis (sleeping sickness) cause by Trypanosoma brucei gambiense.[1] It is effective against both first and second stage disease.[1] Some evidence also supports its use in Chagas disease.[4] It is taken by mouth.[4]

Common side effects include nausea, vomiting, headache, and trouble sleeping.[2] Other side effects may include QT prolongation, psychosis, and low white blood cells.[5] It is unclear if use during pregnancy or breast feeding is safe.[5] Fexinidazole is in the antiparasitic and the nitroimidazole family of medications.[4] It is believed to work by turning on certain enzymes within the parasites that result in their death.[2]

Fexinidazole was first described in 1978.[6] It was given a positive opinion by the European Medicines Agency in 2018 and approved for medical use in the United States in 2021.[2][7] It is on the World Health Organization's List of Essential Medicines.[8] Development for sleeping sickness was funded by the Drugs for Neglected Diseases initiative in collaboration with Sanofi.[9]

Medical use

Sleeping sickness

A trial in Africa found fexinidazole to be 91% effective at treating sleeping sickness.[2][10] Though less effective than nifurtimox with eflornithine in severe disease, fexinidazole has the benefit that it can be taken by mouth.[2]

Fexinidazole is the first drug candidate for the treatment of advanced-stage sleeping sickness in thirty years.[11]


It has activity against Trypanosoma cruzi, Tritrichomonas foetus, Trichomonas vaginalis, Entamoeba histolytica,[12] and Trypanosoma brucei.[13] It has not been found to be useful for visceral leishmaniasis.[4]


The defined daily dose is 1.4 gram.[3]

Mechanism of action

The biologically relevant active metabolites in vivo are the sulfoxide and sulfone.[14][15]


Fexinidazole was discovered by the German pharmaceutical company Hoechst AG, but its development as a pharmaceutical was halted in the 1980s.[16]

Society and culture

Fexinidazole Winthrop, a Sanofi-Aventis product developed with the Drugs for Neglected Diseases Initiative (DNDi), received a positive endorsement from the European Medicines Agency in 2018, for use in non-European markets.[17][18] It was approved for the treatment of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) in December 2018.[19]


  1. 1.0 1.1 1.2 DIMITROVA, Elena Kostadinova (22 January 2019). "Fexinidazole Winthrop H-W-2320". European Medicines Agency. Archived from the original on 18 January 2021. Retrieved 12 November 2019.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 "Fexinidazole Winthrop (fexinidazole)" (PDF). EMA. Archived from the original (PDF) on 2 January 2021. Retrieved 12 November 2019.
  3. 3.0 3.1 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 28 August 2021. Retrieved 10 September 2020.
  4. 4.0 4.1 4.2 4.3 Deeks, ED (February 2019). "Fexinidazole: First Global Approval". Drugs. 79 (2): 215–220. doi:10.1007/s40265-019-1051-6. PMID 30635838.
  5. 5.0 5.1 "Fexinidazole Winthrop" (PDF). EMA. Archived from the original (PDF) on 12 November 2019. Retrieved 12 November 2019.
  6. Gil, Carmen; Rivas, Luis (2017). Drug Discovery for Leishmaniasis. Royal Society of Chemistry. p. 30. ISBN 9781788012584. Archived from the original on 28 August 2021. Retrieved 12 November 2019.
  7. Research, Center for Drug Evaluation and (21 June 2022). "Novel Drug Approvals for 2021". FDA. Archived from the original on 3 March 2022. Retrieved 28 October 2022.
  8. "World Health Organization model list of essential medicines: 21st list 2019". 2019. hdl:10665/325771. {{cite journal}}: Cite journal requires |journal= (help)
  9. "Fexinidazole – DNDi". www.dndi.org. Archived from the original on 29 April 2020. Retrieved 12 November 2019.
  10. Mesu VK, Kalonji WM, Bardonneau C, et al. (4 November 2017). "Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial". Lancet. 391 (10116): 144–154. doi:10.1016/s0140-6736(17)32758-7. ISSN 0140-6736. PMID 29113731.
  11. Torreele, E; Bourdin Trunz, B; Tweats, D; Kaiser, M; Brun, R; Mazué, G; Bray, MA; Pécoul, B (2010). Boelaert, Marleen (ed.). "Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness". PLOS Neglected Tropical Diseases. 4 (12): e923. doi:10.1371/journal.pntd.0000923. PMC 3006138. PMID 21200426.
  12. Raether, W; Seidenath, H (1983). "The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica". Annals of Tropical Medicine and Parasitology. 77 (1): 13–26. PMID 6411009.
  13. Jennings, FW; Urquhart, GM (1983). "The use of the 2 substituted 5-nitroimidazole, Fexinidazole (Hoe 239) in the treatment of chronic T. brucei infections in mice". Zeitschrift für Parasitenkunde. 69 (5): 577–581. doi:10.1007/bf00926669. PMID 6636983.
  14. Wyllie S, Patterson S, Stojanovski L, et al. (2012). "The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis". Science Translational Medicine. 4 (119): 119re1. doi:10.1126/scitranslmed.3003326. PMC 3457684. PMID 22301556.
  15. Sokolova AY, Wyllie S, Patterson S, et al. (2010). "Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis". Antimicrobial Agents and Chemotherapy. 54 (7): 2893–900. doi:10.1128/AAC.00332-10. PMC 2897277. PMID 20439607.
  16. McNeil, Jr., Donald (8 January 2008). "Jump-Start on Slow Trek to Treatment for a Disease". The New York Times. Archived from the original on 29 July 2020. Retrieved 21 February 2017.
  17. "CHMP Summary of Opinion - Fexinidazole Winthrop" (PDF). Archived (PDF) from the original on 24 December 2018. Retrieved 19 November 2018.
  18. McNeil, Jr., Donald (16 November 2018). "Rapid Cure Approved for Sleeping Sickness, a Horrific Illness". The New York Times. Archived from the original on 19 November 2018. Retrieved 20 November 2018.
  19. "Fexinidazole, the first all-oral treatment for sleeping sickness, approved in Democratic Republic of Congo". Drugs for Neglected Diseases Initiative (DNDi). Archived from the original on 14 March 2020. Retrieved 4 June 2019.

External links

External sites: