Nifurtimox

(BAN, rINN)
Nifurtimox Chemical formula
Synonyms: Bayer-2502; Nifurtimoxum. Tetrahydro-3-methyl-4-(5-nitrofurfurylideneamino)-1,4-thiazine 1,1-dioxide.
Cyrillic synonym: Нифуртимокс.

💊 Chemical information

Chemical formula: C10H13N3O5S = 287.3.
CAS — 23256-30-6.
ATC — P01CC01.
ATC Vet — QP51AC01.

Pharmacopoeias.

In Fr. and Int.

💊 Adverse Effects

Adverse effects are common with nifurtimox and include gastrointestinal effects such as anorexia with loss of weight, abdominal pain, nausea and vomiting, and effects on the nervous system, especially peripheral neuropathy. Psychoses, CNS excitement, insomnia, drowsiness, headache, myalgia, arthralgia, dizziness, and convulsions have also been reported. Skin rashes and other allergic reactions may occur.

Mutagenicity.

An increase in chromosomal aberrations has been seen in children given nifurtimox.1
1. Gorla NB, et al. Thirteenfold increase of chromosomal aberrations non-randomly distributed in chagasic children treated with nifurtimox. Mutat Res 1989; 224: 263–7.

💊 Pharmacokinetics

Nifurtimox is well absorbed and rapidly metabolised after oral doses.
1. Paulas C, et al. Pharmacokinetics of a nitrofuran compound, nifurtimox, in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1989; 27: 454–7
2. Gonzalez-Martin G, et al. The pharmacokinetics of nifurtimox in chronic renal failure. Eur J Clin Pharmacol 1992; 42: 671–3.

💊 Uses and Administration

Nifurtimox is a nitrofuran derivative with antiprotozoal activity. It is of value in the treatment of American trypanosomiasis (Chagas’ disease) due to infection by Trypanosoma cruzi, especially the early acute stage of the disease. In African trypanosomiasis it has some activity against T. brucei gambiense, the organism responsible for West African sleeping sickness. Nifurtimox is given orally in 3 to 4 divided doses. It is better tolerated by children than by adults. Treatment for American trypanosomiasis is given for 60 to 120 days (but see below). Doses for adults are 8 to 10 mg/kg daily. Doses for children are: aged 1 to 10 years, 15 to 20 mg/kg daily for 90 days; aged 11 to 16 years, 12.5 to 15 mg/kg daily for 90 days.

Leishmaniasis.

Mucocutaneous leishmaniasis of the New World is usually treated with pentavalent antimony or, in those who do not respond, with amphotericin B or pentamidine. However, nifurtimox 10 mg/kg daily for a minimum of 4 weeks has been shown to be effective in cases of mucocutaneous leishmaniasis in Colombia and Brazil. Despite this, toxic effects with nifurtimox are common and its role as a second-line drug or with pentavalent antimony has not been established.1
1. WHO. Control of the leishmaniases. WHO Tech Rep Ser 793, 1990.

African trypanosomiasis.

Nifurtimox has been tried as an alternative to melarsoprol or eflornithine in the meningoencephalitic stage of Trypanosoma brucei gambiense infection, but higher doses than those used in American trypanosomiasis are necessary. A good initial response was achieved1 in 25 patients with nifurtimox 15 mg/kg daily for 60 days, but 3 patients relapsed while still receiving nifurtimox and a further 12 of 19 patients who were followed up relapsed subsequently. An attempt2 to improve the response by increasing the daily dose even higher to 30 mg/kg for 30 days resulted in substantial toxicity and only a modest improvement in results, with 9 of 25 patients relapsing. However, promising results have been reported3from use of oral nifurtimox 15 mg/kg daily for 10 days with eflornithine 400 mg/kg daily intravenously for 7 days.
1. Pepin J, et al. An open clinical trial of nifurtimox for arsenoresistant Trypanosoma brucei gambiense sleeping sickness in central Zaire. Trans R Soc Trop Med Hyg 1989; 83: 514–17
2. Pépin J, et al. High-dose nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness: an open trial in central Zaire. Trans R Soc Trop Med Hyg 1992; 86: 254–6
3. Priotto G, et al. Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo. Clin Infect Dis 2007; 45: 1435–42.

American trypanosomiasis.

The treatment of American trypanosomiasis is generally unsatisfactory, but nifurtimox is of value especially in the acute phase. However, there has been controversy over its ability to cure completely, that is to eradicate all parasites, in chronic disease.1 Doses recommended by WHO2,3 are 8 to 10 mg/kg daily in three divided doses for adults, and 15 to 20 mg/kg daily in four divided doses for children. WHO recommends that nifurtimox should be given for 60 or 90 days.2,3 Some in the USA4 suggest a 90- to 120-day regimen for adults but nifurtimox is not well tolerated and the experience of other workers1 suggests that few patients may complete the full course.
1. Gutteridge WE. Existing chemotherapy and its limitations. Br Med Bull 1985; 41: 162–8
2. WHO. Control of Chagas disease: second report of the WHO expert committee. WHO Tech Rep Ser 905 2002. Available at: http://libdoc.who.int/trs/WHO_TRS_905.pdf (accessed 17/07/08
3. WHO. WHO model formulary. Geneva: WHO, 2004
4. Abramowicz M, ed. Drugs for parasitic infections. 1st ed. New Rochelle NY: The Medical Letter, 2007.
Published December 11, 2018.