Nifurtimox

Nifurtimox

Clinical data
Trade names	Lampit[1]
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	Undetermined
Routes of administration	By mouth
ATC code	P01CC01 (WHO) QP51AC01 (WHO)
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	Low
Metabolism	Liver (CYP involved)
Biological half-life	2.95 ± 1.19 hours
Excretion	Kidney, very low
Identifiers
IUPAC name N-(3-Methyl-1,1-dioxido-4-thiomorpholinyl)-1-(5-nitro-2-furyl)methanimine
Synonyms	Bayer 2502[1]
CAS Number	23256-30-6 N
PubChem (CID)	31772
ChemSpider	29464 Y
UNII	M84I3K7C2O Y
KEGG	D00833 Y
ChEMBL	CHEMBL290960 N
Chemical and physical data
Formula	C10H13N3O5S
Molar mass	287.293 g/mol
3D model (Jmol)	Interactive image
Chirality	Racemic mixture
Melting point	180 to 182 °C (356 to 360 °F)
SMILES O=S2(=O)CC(N(N=Cc1oc([N+]([O-])=O)cc1)CC2)C
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
NY (what is this?)  (verify)

Nifurtimox is a medication used to Chagas disease and sleeping sickness.^[1][2] For sleeping sickness it is used together with eflornithine.^[2] In Chagas disease it is a second line option to benznidazole.^[3] It is given by mouth.^[1]

Common side effects include abdominal pain, headache, nausea, and weight loss.^[1] There are concerns from animal studies that it may increase the risk of cancer but this concerns have not be found in human trials. Nifurtimox is not recommended in pregnancy or in those with significant kidney or liver problems. It is a type of nitrofuran.^[3]

Nifurtimox came into medication use in 1965.^[3] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.^[2] It is not avaliable commercially in Canada or the United States.^[1] In the United States the medication can be gotten from the Center for Disease Control.^[4] It cost about 20 USD for a course of treatment as of 2013.^[5]

Medical uses

Nifurtimox has been used to treat Chagas disease, when it is given for 30 to 60 days.^[6][7] However, long term use of Nifurtimox does increase chances of adverse events like gastrointestinal and neurological side effects.^[7][8] Due to the low tolerance and completion rate of Nifurtimox, benznidazole is now being more considered for those who have Chagas disease and require long term treatment.^[8][3]

Nifurtimox has also been used to treat African trypanosomiasis (sleeping sickness), and is active in the second stage of the disease (central nervous system involvement). When nifurtimox is given on its own, about half of all patients will relapse,^[9] but the combination of melarsoprol with nifurtimox appears to be efficacious.^[10] Trials are awaited comparing melarsoprol/nifurtimox against melarsoprol alone for African sleeping sickness.^[11]

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.^[12]

Pregnancy and breastfeeding

Use of nifurtimox should be avoided in pregnant women due to limited use.^[7][3][13] There is limited data shown that nifurtimox doses up to 15 mg/kg daily can cause adverse effects in breastfed infants.^[14] Other authors do not consider breastfeeding a contraindication during nifurtimox use.^[14]

Side effects

Side effects occur following chronic administration, particularly in elderly people. Major toxicities include immediate hypersensitivity such as anaphylaxis and delayed hypersensitivity reaction involving icterus and dermatitis. Central nervous system disturbances and peripheral neuropathy may also occur.^[7]

Most common side effects^{[7][4][15][16][17]}

• anorexia
• weight loss
• nausea
• vomiting
• headache
• dizziness
• amnesia

Less common effects^{[7][4][17][15]}

• rash
• depression
• anxiety
• confusion
• fever
• sore throat
• chills
• seizures
• impotence
• tremors
• muscle weakness
• numbness of hands or feet

Contraindications

Nifurtimox is contraindicated in people with severe liver or kidney disease, as well as people with a background of neurological or psychiatric disorders.^[3][18][4]

Mechanism of action

Nifurtimox forms a nitro-anion radical metabolite that reacts with nucleic acids of the parasite causing significant break down of DNA.^[7] Its mechanism is similar to that proposed for the antibacterial action of nitrofuran agents. Nifurtimox undergoes reduction and creates oxygen radicals such as superoxide. These radicals are toxic to T. cruzi. Mammalian cells are protected by presence of catalase, glutathione, peroxidases, and superoxide dismutase. Accumulation of hydrogen peroxide to cytotoxic levels results in parasite death.^[7]

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, where it is sold as 120-mg tablets. It is not commercially available in the United States, but can be distributed to qualifying healthcare professionals by the Centers for Disease Control and Prevention Drug Service.^[7][19][4]

Research

Nifurtimox is in a phase-II clinical trial for the treatment of pediatric neuroblastoma and medulloblastoma.^[20]

References