Nifurtimox, sold under the brand name Lampit, is a medication used to treat

Chagas disease Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by ''Trypanosoma cruzi''. It is spread mostly by insects in the subfamily ''Triatominae'', known as "kissing bugs". The symptoms change over the cou ...

and

sleeping sickness African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species ''Trypanosoma brucei''. Humans are infected by two typ ...

. For sleeping sickness it is used together with

eflornithine Eflornithine, sold under the brand name Vaniqa among others, is a medication used to treat African trypanosomiasis (sleeping sickness) and excessive hair growth on the face in women. Specifically it is used for the 2nd stage of sleeping sickness ...

nifurtimox-eflornithine combination treatment Nifurtimox/eflornithine is a combination of two antiparasitic drugs, nifurtimox and eflornithine, used in the treatment of African trypanosomiasis (sleeping sickness). It is included in the World Health Organization The World Health Organi ...

. In Chagas disease it is a second-line option to

benznidazole Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease this decreases in those who have long-term infection. It is the first-line treatment given its moderate side effe ...

. It is given

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. 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 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

but these concerns have not been found in human trials. Nifurtimox is not recommended in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

or in those with significant kidney or

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the s ...

. It is a type of

nitrofuran Nitrofurans are a class of drugs typically used as antibiotics or antimicrobials. The defining structural component is a furan ring with a nitro group. Drugs Members of this class of drugs include: * Antibacterials (antibiotics) ** Difurazone ...

. Nifurtimox came into medication use in 1965. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. It is not available commercially in Canada. It was approved for medical use in the United States in August 2020. In regions of the world where the disease is common nifurtimox is provided for free by the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...

(WHO).

Medical uses

Nifurtimox has been used to treat

, when it is given for 30 to 60 days. However, long-term use of nifurtimox does increase chances of adverse events like

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

and

neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...

side effects. Due to the low tolerance and completion rate of nifurtimox,

is now being more considered for those who have Chagas disease and require long-term treatment. In the United States nifurtimox is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

in children and adolescents (birth to less than 18 years of age and weighing at least for the treatment of Chagas disease (American Trypanosomiasis), caused by ''Trypanosoma cruzi''. Nifurtimox has also been used to treat

African trypanosomiasis African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species ''Trypanosoma brucei''. Humans are infected by two typ ...

(sleeping sickness), and is active in the second stage of the disease (

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

involvement). When nifurtimox is given on its own, about half of all patients will relapse, but the combination of

melarsoprol Melarsoprol is an arsenic-containing medication used for the treatment of sleeping sickness (African trypanosomiasis). It is specifically used for second-stage disease caused by ''Trypanosoma brucei rhodesiense'' when the central nervous system i ...

with nifurtimox appears to be efficacious. Trials are awaited comparing

/nifurtimox against melarsoprol alone for African sleeping sickness. Combination therapy with

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 Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

and delayed hypersensitivity reaction involving icterus and

dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can v ...

. Central nervous system disturbances and peripheral neuropathy may also occur. Most common side effects * anorexia * weight loss * nausea * vomiting * headache * dizziness * amnesia Less common effects * 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.

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 Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is ef ...

. Nifurtimox undergoes reduction and creates oxygen radicals such as

superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of the ...

. These radicals are toxic to ''T. cruzi''. Mammalian cells are protected by presence of

catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

peroxidase Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides. Functionality Peroxidases typically ca ...

s, and

superoxide dismutase Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen me ...

. Accumulation of hydrogen peroxide to cytotoxic levels results in parasite death.

Society and culture

Legal status

Nifurtimox is only licensed for use in Argentina, the United States, and Germany. 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 Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...

and

medulloblastoma Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa. The brain is divided into two ...

.. Retrieved on July 10, 2009.

References

External links

* {{Portal bar, Medicine Antiprotozoal agents Chagas disease Bayer brands Hydrazones Nitrofurans Sulfones Thiomorpholines World Health Organization essential medicines Wikipedia medicine articles ready to translate Orphan drugs