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Artesunate is a medication used to treat malaria.
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The most common side effects include kidney failure requiring dialysis, hemoglobinuria (the presence of hemoglobin in urine) and jaundice. Side effects may include a slow heartbeat, allergic reaction, dizziness, and low white blood cell levels. Use is likely fine during breastfeeding. It is in the artemisinin class of medication. It is on the World Health Organization's List of Essential Medicines. It was approved for medical use in the United States in May 2020.
Medical uses
Artesunate is the first-line treatment for children or adults with severe malaria, usually in combination with another antimalarial drug. There is moderate-quality evidence that treatment with artesunate plus mefloquine is superior to treatment with artesunate plus amodiaquine or artesunate plus sulfadoxine-pyrimethamine. Artemisinin-based combination therapy may be used by mouth in persons that can tolerate it after 24 hours by injection.
Artesunate is preferred over parenteral quinine for severe malaria treatment. and Asia. A subsequent systematic review of seven randomized controlled trials found this improvement in survival rates to be consistent across all trials.
Artesunate's efficacy is comparable to that of artemether, another artemisinin derivative, in treating adults for severe malaria caused by Plasmodium falciparum, though artesunate clears more parasites initially. Artesunate combination drugs have a number of advantages over artemether-based drugs in terms of its uptake and administration routes and may be more effective in treatment of severe and complicated malaria in children.
Artesunate is also used to treat less-severe forms of malaria when it can be given orally. but has not been evaluated in large randomized trials.
Artesunate is used as the treatment of choice for severe malaria by the World Health Organization (WHO) over quinine. However, there is insufficient evidence regarding the safety of artesunate use in the first trimester of pregnancy. The WHO recommends that artesunate use for severe malaria in the first trimester should be based on the individual risks versus benefits. In absence of other viable treatment options, artesunate may be used.
Children
Artesunate is safe for use in children. Artesunate + sulfadoxine/pyrimethamine should be avoided in the newborns due to sulfadoxine/pyrmethamine effects on bilirubin.
Artesunate is generally safe and well tolerated. Artesunate-based regimens are less likely to cause vomiting and tinnitus than quinine plus anti-malarial antibiotic therapy. The best recognised adverse effect of the artemisinins is that they lower reticulocyte counts. This is not usually of clinical relevance.
With increased use of I.V. artesunate, there have been reports of post-artesunate delayed haemolysis (PADH). Delayed haemolysis (occurring around two weeks after treatment) has been observed in people treated with artesunate for severe malaria.
Contraindications
Artesunate is typically a well tolerated medicine. Known contraindications include a previous severe allergic reaction to artesunate.
Drugs that should be avoided while on artesunate are the drugs that inhibit the liver enzyme CYP2A6. These drugs include amiodarone, desipramine, isoniazid, ketoconazole, letrozole, methoxsalen and tranylcypromine.
Mechanisms of action
The mechanisms of action of artesunate remains unclear and debatable. Artesunate is a prodrug that is rapidly converted to its active form dihydroartemisinin (DHA). This process involves hydrolysis of the 4-carbon ester group via plasma esterase enzyme. It is hypothesized that the cleavage of endoperoxide bridge in the pharmacophore of DHA generates reactive oxygen species (ROS), which increases oxidative stress and causes malarial protein damage via alkylation. As a result, the amount of glutathione in the parasite is reduced.
In 2016, artemisinin has been shown to bind to a large number targets, suggesting that it acts in a promiscuous manner. There is evidence suggesting DHA inhibition of calcium-dependent ATPase on endoplasmic membrane, which disrupts protein folding of parasites.
Pharmacokinetics
In infected individuals, the elimination half-life of artesunate is about 0.22 hours. Its active metabolite, DHA, has a slightly longer half-life of 0.34 hours. Overall, the average half-life ranges from 0.5 to 1.5 hours. Because of its short half-life, its use in malaria prevention is limited.
Chemical synthesis
Artesunate is made from dihydroartemisinin (DHA) by reacting it with succinic acid anhydride in a basic medium. It is one of few semi-synthetic derivatives from artemisinin that is water-soluble.
Research
Artesunate is under study for the treatment of COVID-19.
History
In May 2020, artesunate was approved for medical use in United States. Prior to this approval, intravenous (IV) artesunate was only available through the Expanded Access program of the U.S. Food and Drug Administration (FDA), which allowed the Centers for Disease Control and Prevention (CDC) to provide IV artesunate to people in the U.S. with severe malaria and to people with uncomplicated malaria who are unable to take oral medications under an investigational new drug (IND) protocol. The FDA granted approval of artesunate for injection to Amivas.