Medical uses[edit]
Artesunate is the first line treatment for children or adults with severe malaria.
[10] The recommendation is to treat with at least 24 hours of artesunate by injection.
Artemisinin-based combination therapy may be used by mouth in persons that can tolerate it after 24 hours by injection. In facilities where long-term care is not appropriate, artesunate may be given as a single intramuscular injection or by rectal route (children < 6 years) prior to transferring care to a higher level facility.
Artesunate is preferred over parenteral quinine for severe malaria treatment.
[3] Artesunate was shown to prevent more deaths from severe malaria than quinine in two large multicentre randomized controlled trials from Africa
[11] and Asia.
[12]A subsequent systematic review of seven randomized controlled trials found this improvement in survival rates to be consistent across all trials.
[13]
While artesunate is used primarily as treatment for malaria, there is some evidence that it may also have some beneficial effects in
Schistosoma haematobium infection,
[14] but has not been evaluated in large randomized trials.
Pregnancy[edit]
When given in the second or third trimesters of pregnancy, no artesunate-related adverse pregnancy outcomes have been reported.
[15] 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[edit]
Artesunate is safe for use in children. Artesunate + sulfadoxine/pyrimethamine should be avoided in the newborns due to sulfadoxine/pyrmethamine effects on bilirubin.
[10] Parenteral artesunate dosing for treatment of severe malaria in children less than 20 kg should be higher than that of adults in order to increase exposure.
[10] When artesunate cannot be given orally or intramuscularly due to an individual's weakness or inability to swallow, rectal administration may be given as pre-referral treatment as long as parenteral administration is initiated after transfer to a more advanced facility.
Adverse effects[edit]
Artesunate is generally safe and well-tolerated. The best recognised side effect of the artemesinins is that they lower
reticulocyte counts.
[16] This is not usually of clinical relevance.
With increased use of I.V. artesunate, there have been reports of post-artesunate delayed
haemolysis (PADH).
[17] Delayed haemolysis (occurring around two weeks after treatment) has been observed in patients treated with artesunate for severe malaria.
[18] It is unclear whether or not this haemolysis is due to artesunate or to the malaria itself.
[19]
Contraindications[edit]
Artesunate is typically a well tolerated medicine. Known contraindications include a previous severe allergic reaction to artesunate.
[20]
Mechanisms of action[edit]
In 2016, artemisinin has been shown to bind to a large number targets, suggesting that it acts in a promiscuous manner.
[24] There is evidence suggesting DHA inhibition of calcium-dependent ATPase on endoplasmic membrane, which disrupts protein folding of parasites.
[22]
Pharmacokinetics[edit]
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.
[25] Because of its short half-life, its use in malaria prevention is limited.
[22]
Chemical synthesis[edit]
.jpg)
