Nifurtimox

Nifurtimox

Systematic (IUPAC) name
(RS)-3-methyl-N-[(1E)-(5-nitro-2-furyl)methylene]thiomorpholin-4-amine 1,1-dioxide
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy cat.	Undetermined
Legal status	℞ Prescription only Not available in U.S. or Canada
Routes	Oral
Pharmacokinetic data
Bioavailability	Low
Metabolism	Hepatic (CYP involved)
Half-life	2.95 ± 1.19 hours
Excretion	Renal, very low
Identifiers
CAS number	23256-30-6 Y
ATC code	P01CC01 QP51AC01
PubChem	CID 31772
ChemSpider	29464 Y
UNII	M84I3K7C2O N
KEGG	D00833 Y
ChEMBL	CHEMBL290960 N
Chemical data
Formula	C10H13N3O5S
Mol. mass	287.293 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C10H13N3O5S/c1-8-7-19(16,17)5-4-12(8)11-6-9-2-3-10(18-9)13(14)15/h2-3,6,8H,4-5,7H2,1H3 Y Key:ARFHIAQFJWUCFH-UHFFFAOYSA-N Y
N(what is this?)  (verify)

Nifurtimox is a 5-nitrofuran and is used to treat diseases caused by trypanosomes including Chagas disease and sleeping sickness. It is given by mouth and not by injection.

Indications

Nifurtimox has been used to treat Chagas disease, when it is given for 30 to 60 days,^[1] but gastrointestinal and neurological side effects have meant that benznidazole is now preferred for that indication.

Nifurtimox has also been used to treat African trypanosomiasis (sleeping sickness), and is active in the second stage of the disease (CNS involvement). When nifurtimox is given on its own, about half of all patients will relapse,^[2] but the combination of melarsoprol with nifurtimox appears to be efficacious.^[3] Trials are awaited comparing melarsoprol/nifurtimox against melarsoprol alone for African sleeping sickness.^[4]

Combination therapy with eflornithine and nifurtimox is safer and easier than treatment with eflornithine alone, and appears to be equally or more effective. It has been recommended as first-line treatment for second-stage African trypanosomiasis.^[5]

Investigational

Nifurtimox is in a Phase II clinical trial for the treatment of pediatric neuroblastoma and medulloblastoma.^[6][7]

Dosing

Nifurtimox is dosed as 15 mg/kg/day in two to three divided doses. It is given by mouth. Refer to the articles on Chagas disease and sleeping sickness for more detailed information on dosing for these diseases.

Manufacturing and availability

Nifurtimox is sold as Lampit by Bayer. It was previously known as Bayer 2502.

Nifurtimox is only licensed for use in Argentina and Germany,^{[citation needed]} where it is sold as 120 mg tablets.

References

1. ^ Coura JR, de Castro SL. (2002). "A critical review of Chagas disease chemotherapy". Mem Inst Oswaldo Cruz 97 (1): 3–24. doi:10.1590/S0074-02762002000100001. PMID 11992141. 
2. ^ Pepin J, Milord F, Mpia B, et al. (1989). "An open clinical trial of nifurtimox for arseno-resistant T.b. gambiense sleeping sickness in central Zaire". Trans R Soc Trop Med Hyg 83 (4): 514–7. doi:10.1016/0035-9203(89)90270-8. PMID 2694491. 
3. ^ Bisser S, N'Siesi F-X, Lejon V, et al. (2007). "Equivalence Trial of Melarsoprol and Nifurtimox Monotherapy and Combination Therapy for the Treatment of Second-Stage Trypanosoma brucei gambiense Sleeping Sickness". J Infect Dis 195 (3): 322–329. doi:10.1086/510534. PMID 17205469. 
4. ^ Pepin J (2007). "Combination Therapy for Sleeping Sickness: A Wake-Up Call". J Infect Dis 195 (3): 311–13. doi:10.1086/510540. PMID 17205466. 
5. ^ Priotto G, Kasparian S, Mutombo W, et al. (July 2009). "Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial". Lancet 374 (9683): 56–64. doi:10.1016/S0140-6736(09)61117-X. PMID 19559476. 
6. ^ ClinicalTrials.gov NCT00601003 . Retrieved on July 10, 2009.
7. ^ "A phase II trial of nifurtimox for refractory or relapsed neuroblastoma or medulloblastoma (VCC 0706)". Vermont Cancer Center. http://www.vermontcancer.org/index.php?id=232. Retrieved 2009-07-10.