Nifurtimox

Structural formula
	( R ) shape (top) and ( S ) shape (bottom)
General
Non-proprietary name	Nifurtimox
other names	( RS ) - N - (3-methyl-1,1-dioxo-1,4-thiazinan-4-yl) -1- (5-nitro-2-furyl) methanimine ( IUPAC )
Molecular formula	C 10 H 13 N 3 O 5 S
External identifiers / databases
EC number	245-531-0
ECHA InfoCard	100,041,377
PubChem	6842999
Wikidata	Q411582
Drug information
ATC code	P01 CC01
Drug class	Antiprotozoic
properties
Molar mass	287.29 g · mol -1
Physical state	firmly
Melting point	180-182 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 373
	P: ?
Toxicological data	2 g kg −1 ( LD 50 , rabbit , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Nifurtimox ( trade name Lampit ) is a drug from the group of nitrofurans , which is used as an antiprotozoal for the treatment of Chagas disease .

Clinical information

Nifurtimox is recommended by the WHO for the treatment of acute Chagas disease, an infection with Trypanosoma cruzi . There is insufficient information to prove its effectiveness in chronic Chagas disease as well.

In addition to Chagas disease, the use of nifurtimox in combination therapy with eflornithine for the treatment of the late stage of West African sleeping sickness , an infection with a subspecies of Trypanosoma brucei , is currently being investigated. An effect in the treatment of neuroblastomas and medulloblastomas is currently being tested after a remission of a neuroblastoma was observed in the treatment of a patient suffering from Chagas' disease.

More common side effects include weight loss and anorexia, psychological changes, irritability or drowsiness, and gastrointestinal disorders such as diarrhea and vomiting. Animal experiments provide evidence of neurotoxicity, toxicity in the testes and ovaries, and harmful effects in the adrenal glands, colon, esophagus and mammary glands.

Nifurtimox should not be used during pregnancy; there is evidence that the substance is mutagenic .

Pharmacological properties

After oral administration it is well absorbed and practically completely metabolized. Nifurtimox probably works via the formation of free radicals, which the parasite can hardly break down.

Other Information

Nifurtimox was developed in the 1960s under the name "Bayer 2502" at Bayer AG . The substance has been used against Chagas disease since 1967; besides benznidazole, it is the only substance available for the treatment of this disease. No nifurtimox preparations are currently approved in Germany, Austria or Switzerland; in South America tablets with 120 mg of active ingredient are available. After Bayer ceased production in 1997 due to a lack of demand, production was resumed in 2000 to enable clinical studies in African sleeping sickness. Thanks to agreements between the WHO and Bayer and the manufacturer's drug donations, the supply of nifurtimox is now considered to be secure again.

Individual evidence

^ The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X , p. 1131.
↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of nifurtimox in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was retrieved on July 8, 2020, is reproduced from a self-classification by the distributor .
↑ Entry on Nifurtimox in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on July 8, 2020.
↑ WHO Chagas disease , accessed on 13 August 2012 found.
^ PA Reyes, M. Vallejo: Trypanocidal drugs for late stage, symptomatic Chagas disease (Trypanosoma cruzi infection). In: Cochrane Database Syst Rev. (4), October 19, 2005, Art. No. CD004102. PMID 16235350 .
↑ F. Checchi, P. Piola, H. Ayikoru, F. Thomas, D. Legros, G. Priotto: Nifurtimox plus Eflornithine for Late-Stage Sleeping Sickness in Uganda: A Case Series. In: PLoS Negl Trop Dis. 1 (2), November 7, 2007, p. E64. PMID 18060083 .
↑ Phase II clinical study with nifurtimox in neuroblastomas .
↑ GL Saulnier Sholler, S. Kalkunte, C. Greenlaw, K. McCarten, E. Forman: Antitumor activity of nifurtimox observed in a patient with neuroblastoma. In: J Pediatr Hematol Oncol. 28 (10), October 2006, pp. 693-695. PMID 1702383 .
↑ ^a ^b ^c J. Rodriques Coura, SL de Castro: A critical review on Chagas disease chemotherapy. In: Mem Inst Oswaldo Cruz. 97 (1), Jan 2002, pp. 3-24. PMID 11992141 .
↑ JA Castro, MM de Mecca, LC Bartel: Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis). In: Hum Exp Toxicol . 25 (8), August 2006, pp. 471-479. PMID 16937919 .
↑ J. Jannin, L. Villa: An overview of Chagas disease treatment. In: Mem Inst Oswaldo Cruz. 102 Suppl 1, October 30, 2007, pp. 95-97. PMID 17906803 .

[MERCK_Index-1] The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ, USA, 2006, ISBN 0-911910-00-X , p. 1131.

[2] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of nifurtimox in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was retrieved on July 8, 2020, is reproduced from a self-classification by the distributor .

[ChemIDplus-3] Entry on Nifurtimox in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on July 8, 2020.

[4] WHO Chagas disease , accessed on 13 August 2012 found.

[5] PA Reyes, M. Vallejo: Trypanocidal drugs for late stage, symptomatic Chagas disease (Trypanosoma cruzi infection). In: Cochrane Database Syst Rev. (4), October 19, 2005, Art. No. CD004102. PMID 16235350 .

[6] F. Checchi, P. Piola, H. Ayikoru, F. Thomas, D. Legros, G. Priotto: Nifurtimox plus Eflornithine for Late-Stage Sleeping Sickness in Uganda: A Case Series. In: PLoS Negl Trop Dis. 1 (2), November 7, 2007, p. E64. PMID 18060083 .

[7] Phase II clinical study with nifurtimox in neuroblastomas .

[8] GL Saulnier Sholler, S. Kalkunte, C. Greenlaw, K. McCarten, E. Forman: Antitumor activity of nifurtimox observed in a patient with neuroblastoma. In: J Pediatr Hematol Oncol. 28 (10), October 2006, pp. 693-695. PMID 1702383 .

[Coura-9] J. Rodriques Coura, SL de Castro: A critical review on Chagas disease chemotherapy. In: Mem Inst Oswaldo Cruz. 97 (1), Jan 2002, pp. 3-24. PMID 11992141 .

[10] JA Castro, MM de Mecca, LC Bartel: Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis). In: Hum Exp Toxicol . 25 (8), August 2006, pp. 471-479. PMID 16937919 .

[11] J. Jannin, L. Villa: An overview of Chagas disease treatment. In: Mem Inst Oswaldo Cruz. 102 Suppl 1, October 30, 2007, pp. 95-97. PMID 17906803 .