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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 is involved. For Trypanosoma brucei gambiense, eflornithine or fexinidazole is usually preferred. It is effective in about 95% of people. It is given by intravenous and is known by patients as "fire in the veins".
Melarsoprol has a high number of side effects. Common side effects include encephalopathy, numbness, rashes, and kidney and liver problems. About 1–5% of people die during treatment, although this is tolerated due to sleeping sickness itself having a practically 100% mortality rate when untreated. In those with glucose-6-phosphate dehydrogenase (G6PD) deficiency, hemolysis may occur. It has not been studied in pregnancy. While its mechanism of action is not fully understood, its covalent binding to trypanothione to form the toxic Mel T complex is thought to play a large role.
Melarsoprol has been used medically since 1949. It is on the World Health Organization's List of Essential Medicines. In regions of the world where the disease is common, melarsoprol is provided for free by the World Health Organization. It is not commercially available in Canada or the United States. In the United States, it may be obtained from the Centers for Disease Control and Prevention, while in Canada it is available from Health Canada.
The following are considerable treatment options:
Melarsoprol is a treatment used during the second stage of the disease. So far, it is the only treatment available for late-stage T. b. rhodesiense.
Due to high toxicity, melarsoprol is reserved only for the most dangerous cases. Other agents associated with lower toxicity levels are used during stage 1 of the disease. The approval of the nifurtimox-eflornithine combination therapy (NECT) in 2009 for the treatment of T. b. gambiense limited the use of melarsoprol to the treatment of second-stage T. b. rhodesiense. (2025). 9780702053061, Elsevier Saunders. ISBN 9780702053061
Failure rates of 27% in certain African countries have been reported. This was caused by both drug resistance and additional mechanisms that have not yet been elucidated. Resistance is likely due to transport problems associated with the P2 transporter, an adenine-adenosine transporter. Resistance can occur with point mutations within this transporter. Resistance has been present since the 1970s.
In August 2024. the World Health Organization recommended fexinidazole, developed by the Drugs for Neglected Diseases initiative and partners to replace melarsoprol as the first-line treatment for sleeping sickness caused by T.b. rhodesiense.
Melarsoprol used for the treatment of African trypanosomiasis with CNS involvement is given under a complicated dosing schedule. The dosing schedule for children and adults is 2–3.6 mg/kg/day intravenously for three days, then repeated every seven days for a total of three series. To monitor for relapse, follow-up is recommended every six months for at least two years.
Lactation guidelines associated with melarsoprol have not yet been established.
Routine laboratory testing is needed before and after melarsoprol initiation. Laboratory parameters for both therapeutic effects and toxic effects need to be evaluated.
Blood analysis is used to detect the presence of trypanosomes. An evaluation of the cerebrospinal fluid via a lumbar puncture is also used to determine an individual's white blood count and level of protein. These are diagnostic criteria such that the presence of trypanosomes, an elevated white blood count greater than five per microliter, or a protein content greater than 40 mg are considered abnormal and initiation should be considered. Continuous cerebrospinal fluid evaluation should be repeated every six months for at least three years in individuals that have undergone melarsoprol treatment.
To assess potential concerns related to toxicity, the following should be completed: a complete blood count, an assessment of electrolyte levels, liver and kidney function tests, and a urinalysis to detect the appearance, concentration and content of the urine.
Melarsoprol should be given using glass syringes (if they can be reliably sterilized). The propylene glycol it contains is capable of dissolving plastic.
...cites this study:
While the exact mechanism of action of melarsoprol has not been determined beyond the formation of Mel T, it has been suggested that this complex is implicated in several cytotoxic processes, including inhibition of DNA synthesis and increasing susceptibility to oxidative stress. This follows from the fact that trypanothione itself plays a role in the proper function of a variety of biochemical pathways.
Melarsoprol was used to treat a patient with second-stage African trypanosomiasis on season 1 episode 7 "Fidelity" of the medical drama House MD.
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