Nifurtimox

Nifurtimox has been used to treat Chagas disease, when it is given for 30 to 60 days. However, long-term use of nifurtimox does increase chances of adverse events like gastrointestinal and neurological side effects. 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. 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, but the combination of melarsoprol with nifurtimox appears to be efficacious. Trials are awaited comparing melarsoprol/nifurtimox against melarsoprol alone for African sleeping sickness. 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. Pregnancy and breastfeeding Use of nifurtimox should be avoided in pregnant women due to limited use. There is limited data shown that nifurtimox doses up to 15 mg/kg daily can cause adverse effects in breastfed infants. Other authors do not consider breastfeeding a contraindication during nifurtimox use. ==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. • anorexia • weight loss • nausea • vomiting • headache • dizziness • amnesia Less common effects == Mechanism of action ==

Nifurtimox forms a nitro-anion radical metabolite that reacts with nucleic acids of the parasite causing significant breakdown of DNA. Its mechanism is similar to that proposed for the antibacterial action of metronidazole. 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. == Society and culture ==

Legal status Nifurtimox is licensed for use in Argentina, the United States, Turkey and Germany amongst others. It was approved for medical use in the United States in August 2020. Names ==Research==

Nifurtimox is in a phase-II clinical trial for the treatment of pediatric neuroblastoma and medulloblastoma. == References ==