Nifurtimox Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:462260534
Width:250px
Width2:220px
Chirality:Racemic mixture
Tradename:Lampit
Drugs.Com:
Dailymedid:Nifurtimox
Routes Of Administration:By mouth
Atc Prefix:P01
Atc Suffix:CC01
Legal Us:Rx-only
Legal Status:Rx-only
Bioavailability:Low
Metabolism:Liver (Cytochrome P450 oxidase (CYP) involved)
Elimination Half-Life:2.95 ± 1.19 hours
Excretion:Kidney, very low
Cas Number:23256-30-6
Pubchem:6842999
Drugbank:DB11820
Chemspiderid:29464
Unii:M84I3K7C2O
Kegg:D00833
Kegg2:C08002
Chebi:7566
Chembl:290960
Synonyms:Bayer 2502
Iupac Name:N-(3-Methyl-1,1-dioxido-4-thiomorpholinyl)-1-(5-nitro-2-furyl)methanimine
C:10
H:13
N:3
O:5
S:1
Smiles:CC1CS(=O)(=O)CCN1N=CC2=CC=C(O2)[N+](=O)[O-]
Stdinchi: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
Stdinchikey:ARFHIAQFJWUCFH-UHFFFAOYSA-N
Melting Point:180
Melting High:182

Nifurtimox, sold under the brand name Lampit, is a medication used to treat Chagas disease and sleeping sickness. For sleeping sickness it is used together with eflornithine in nifurtimox-eflornithine combination treatment. In Chagas disease it is a second-line option to benznidazole. It is given by mouth.

Common side effects include abdominal pain, headache, nausea, and weight loss. There are concerns from animal studies that it may increase the risk of cancer but these concerns have not been 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.

Nifurtimox came into medication use in 1965.[1] It is on the World Health Organization's List of Essential Medicines.[2] It is not available commercially in Canada.[3] It was approved for medical use in the United States in August 2020.[4] In regions of the world where the disease is common nifurtimox is provided for free by the World Health Organization (WHO).[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.[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.[1]

In the United States nifurtimox is indicated in children and adolescents (birth to less than 18 years of age and weighing at least 2.5kg (05.5lb) for the treatment of Chagas disease (American Trypanosomiasis), caused by Trypanosoma cruzi.[9]

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,[10] but the combination of melarsoprol with nifurtimox appears to be efficacious.[11] Trials are awaited comparing melarsoprol/nifurtimox against melarsoprol alone for African sleeping sickness.[12]

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.[13]

Pregnancy and breastfeeding

Use of nifurtimox should be avoided in pregnant women due to limited use.[14] There is limited data shown that nifurtimox doses up to 15 mg/kg daily can cause adverse effects in breastfed infants.[15] 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.

Most common side effects[16] [17] [18] [19]

Less common effects

Contraindications

Nifurtimox is contraindicated in people with severe liver or kidney disease, as well as people with a background of neurological or psychiatric disorders.[1] [20]

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.[21]

External links

Notes and References

  1. Bern C, Montgomery SP, Herwaldt BL, Rassi A, Marin-Neto JA, Dantas RO, Maguire JH, Acquatella H, Morillo C, Kirchhoff LV, Gilman RH, Reyes PA, Salvatella R, Moore AC . 6 . Evaluation and treatment of chagas disease in the United States: a systematic review . JAMA . 298 . 18 . 2171–2181 . November 2007 . 18000201 . 10.1001/jama.298.18.2171 . free .
  2. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  3. Web site: Nifurtimox (Systemic). 1995. Drugs.com. 3 December 2016. live. https://web.archive.org/web/20161220042503/https://www.drugs.com/cons/nifurtimox.html. 20 December 2016.
  4. Web site: Lampit: FDA-Approved Drugs . U.S. Food and Drug Administration (FDA) . 6 August 2020.
  5. Web site: Trypanosomiasis, human African (sleeping sickness). World Health Organization. 7 December 2016. February 2016. live. https://web.archive.org/web/20161204153318/http://www.who.int/mediacentre/factsheets/fs259/en/. 4 December 2016.
  6. Rodriques Coura J, de Castro SL . A critical review on Chagas disease chemotherapy . Memórias do Instituto Oswaldo Cruz . 97 . 1 . 3–24 . January 2002 . 11992141 . 10.1590/S0074-02762002000100001 . free .
  7. Web site: Nifurtimox Drug Information, Professional. www.drugs.com. 2016-11-09. live. https://web.archive.org/web/20161108140805/https://www.drugs.com/mmx/nifurtimox.html. 2016-11-08.
  8. Jackson Y, Alirol E, Getaz L, Wolff H, Combescure C, Chappuis F . Tolerance and safety of nifurtimox in patients with chronic chagas disease . Clinical Infectious Diseases . 51 . 10 . e69–e75 . November 2010 . 20932171 . 10.1086/656917 . free .
  9. Web site: Lampit- nifurtimox tablet, film coated . DailyMed . 27 January 2022 . 23 February 2023.
  10. Pepin J, Milord F, Mpia B, Meurice F, Ethier L, DeGroof D, Bruneel H . An open clinical trial of nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness in central Zaire . Transactions of the Royal Society of Tropical Medicine and Hygiene . 83 . 4 . 514–517 . 1989 . 2694491 . 10.1016/0035-9203(89)90270-8 .
  11. Bisser S, N'Siesi FX, Lejon V, Preux PM, Van Nieuwenhove S, Miaka Mia Bilenge C, Būscher P . Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness . The Journal of Infectious Diseases . 195 . 3 . 322–329 . February 2007 . 17205469 . 10.1086/510534 . free .
  12. Pepin J . Combination therapy for sleeping sickness: a wake-up call . The Journal of Infectious Diseases . 195 . 3 . 311–313 . February 2007 . 17205466 . 10.1086/510540 . free .
  13. Priotto G, Kasparian S, Mutombo W, Ngouama D, Ghorashian S, Arnold U, Ghabri S, Baudin E, Buard V, Kazadi-Kyanza S, Ilunga M, Mutangala W, Pohlig G, Schmid C, Karunakara U, Torreele E, Kande V . 6 . 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 . July 2009 . 19559476 . 10.1016/S0140-6736(09)61117-X . free . 32757305 . 10144/72797 .
  14. Book: Padberg S . Anti-infective agents: Nitrofurans and drugs for urinary infection . https://books.google.com/books?id=L2NzAwAAQBAJ&q=Nifurtimox+pregnancy&pg=PA124 . Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment. Schaefer C, Peters PW, Miller RK . 2014-09-17. Academic Press. 9780124079014. live. https://web.archive.org/web/20170908221306/https://books.google.com/books?id=L2NzAwAAQBAJ&pg=PA124&lpg=PA124&dq=Nifurtimox+pregnancy&source=bl&ots=XzIcQyHD_0&sig=_2ucLo3S4ng_MtnTsjGknCbCXtM&hl=en&sa=X&ved=0ahUKEwiR486g5ZfQAhVkslQKHUVFCysQ6AEIVTAI#v=onepage&q=Nifurtimox%20pregnancy&f=false. 2017-09-08.
  15. Web site: Nifurtimox use while Breastfeeding . Drugs.com. 2016-11-07. live. https://web.archive.org/web/20161108140741/https://www.drugs.com/breastfeeding/nifurtimox.html. 2016-11-08.
  16. Web site: Parasites - American Trypanosomiasis (also known as Chagas Disease) . U.S. Centers for Disease Control and Prevention (CDC) . 2016-11-09 . live . https://web.archive.org/web/20161106123343/http://www.cdc.gov/parasites/chagas/health_professionals/tx.html . 2016-11-06.
  17. Forsyth CJ, Hernandez S, Olmedo W, Abuhamidah A, Traina MI, Sanchez DR, Soverow J, Meymandi SK . 6 . Safety Profile of Nifurtimox for Treatment of Chagas Disease in the United States . Clinical Infectious Diseases . 63 . 8 . 1056–1062 . October 2016 . 27432838 . 5036918 . 10.1093/cid/ciw477 .
  18. Castro JA, de Mecca MM, Bartel LC . Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis) . Human & Experimental Toxicology . 25 . 8 . 471–479 . August 2006 . 16937919 . 10.1191/0960327106het653oa . 2006HETox..25..471C . free . 8980212 . 11336/82805 .
  19. Sosa Estani S, Segura EL . Treatment of Trypanosoma cruzi infection in the undetermined phase. Experience and current guidelines of treatment in Argentina . Memórias do Instituto Oswaldo Cruz . 94 . 363–365 . 1999-09-01 . Suppl 1 . 10677756 . 10.1590/S0074-02761999000700070 . free .
  20. Web site: Chagas disease. World Health Organization. 2016-11-08. live. https://web.archive.org/web/20140227181940/http://www.who.int/mediacentre/factsheets/fs340/en/. 2014-02-27.
  21. . Retrieved on July 10, 2009.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Nifurtimox".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.