Artesunate 50mg Medical Tablets For treatment of cerebral malaria
and all kinds of critical malaria
Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinidine for severe malaria. Often it is used as part of combination therapy. It is not used for the prevention of malaria. Artesunate can be given by injection into a vein, injection into a muscle, or taken by mouth.
Artesunate is generally well tolerated. Side effects may include a slow heartbeat, allergic reaction, dizziness, and low white blood cell levels.During pregnancy it appears to be a safer option, even though animal studies have
found harm to the baby. Use is likely okay during breastfeeding.It is in the artemisinin class of medication.
Artesunate is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is 2.09 to 2.57 USD a dose. It is not commercially available in the United States; however, can
be gotten from the Centers for Disease Control. It was originally made from the sweet wormwood plant.
Artesunate is the first line treatment for children or adults with
severe malaria. 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.Artesunate was shown to prevent more deaths from severe malaria
than quinine in two large multicentre randomized controlled trials
from Africa and Asia. A subsequent systematic review of seven randomized controlled
trials found this improvement in survival rates to be consistent
across all trials.
Artesunate is also used to treat less severe forms of malaria when
it can be given orally. It has activity against P. ovale, P. malariae, and severeP. knowlesi.
Artesunate + sulfadoxine/pyrimethamine for treatment of P. vivax is not recommended due to high rates of resistance.
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, but has not been evaluated in large randomized trials.
Although not FDA-approved for use in the United States, artesunate is used as the
treatment of choice for severe malaria by the World Health Organization (WHO) over quinidine.
When given in the second or third trimesters of pregnancy, no
artesunate-related adverse pregnancy outcomes have been reported. 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
Artesunate is safe for use in children. Artesunate +
sulfadoxine/pyrimethamine should be avoided in the newborns due to
sulfadoxine/pyrmethamine effects on bilirubin. 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.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
Artesunate is generally safe and well-tolerated. The best
recognised side effect of the artemesinins 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 patients treated with artesunate for severe
malaria. It is unclear whether or not this haemolysis is due to artesunate
or to the malaria itself.
Artesunate is typically a well tolerated medicine. Known
contraindications include a previous severe allergic reaction to
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,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 involveshydrolysis 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. In addition, Artesunate potently inhibits the essential Plasmodium falciparum exported protein 1 (EXP1), a membrane glutathione S-transferase. 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
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
DHA is metabolized to an inactive metabolite by the liver enzymes CYP2B6, CYP2C19, and CYP3A4.
Artesunate is made from dihydroartemisinin (DHA) by reacting it with succinic acid anhydride in a basic medium. It is one of many semi-synthetic derivatives from Artemisinin that is water-soluble.
[Pharmacology and toxicology]
This product is on the ultrastructure of rat blood stage Plasmodium
effect is mainly Plasmodium membrane structure changes, the
medicine in the role of the first food vacuole membrane, membrane,
mitochondria, followed by nuclear membrane, endoplasmic reticulum,
in addition to the nuclear chromatin also have certain effect. It
is suggested that the main mode of action of this product is to
interfere with the function of membrane mitochondria. This product
may be acting on the food vacuole membrane, thereby blocking the
earliest stage of nutrient uptake, the rapid emergence of
Plasmodium amino acid starvation, the rapid formation of autophagic
vacuoles, and continue to discharge the insect body, so that the
loss of cytoplasm and death of plasmodium. The uptake of tritiated
isoleucine by Plasmodium falciparum cultured in vitro also suggests
that its initial mode of action may be to inhibit the synthesis of
protozoan proteins. Animal toxicology experiments show that the
product has obvious embryonic toxicity.
After oral administration, the body is widely distributed, and the
intestine, liver and kidney are higher. Mainly metabolic
transformation in vivo. Excreted only by urine and feces.
Store in a cool & dry place, protect from the light, keep out
of the reach of the children.