Artesunate is a medication primarily used in the treatment of malaria. It belongs to the artemisinin class of drugs, which are derived from the sweet wormwood plant (Artemisia annua). Artesunate is known for its rapid onset of action and effectiveness against malaria parasites, including those that are resistant to other antimalarial drugs.

Artesunate works by generating toxic free radicals within the malaria parasite, leading to its destruction. It is often used in combination with other antimalarial medications to prevent the development of resistance and to increase efficacy.

Artesunate is an antimalarial prodrug that is activated to the active compound dihydroartemisinin. It is active against all the erythrocytic stages of malarial infection including gametocytes. It does not eradicate the liver stages of malaria (hypnozoites)

It used to treat patients with severe malaria.

Artesunate Dose in Adults

Artesunate Dose in the treatment of Severe Malaria:  

• The usual dose of Artesunate given through injection into a muscle (IM) or into a vein (IV) is 2.4 milligrams per kilogram (mg/kg) of body weight initially.
• Then, the same dose is repeated at 12 hours, 24 hours, and 48 hours after the first dose, for a total of four doses over three days.
• In some cases, especially if the patient is very sick or can't switch to oral medicine, treatment might need to continue for longer, possibly up to an extra four days.
• After the last dose of Artesunate, patients should transition to oral medicine at least four hours later.
• Suitable oral medicines include atovaquone-proguanil, doxycycline (for patients older than eight years and non-pregnant adults), clindamycin, or mefloquine.

Artesunate Dose in Children

Artesunate Dose in the treatment of Severe Malaria:

Infants, Children, and Adolescents:

• For patients weighing less than 20 kilograms, the usual dose given through injection into a muscle (IM) or into a vein (IV) is 3 milligrams per kilogram (mg/kg) of body weight initially. Then, the same dose is repeated at 12 hours, 24 hours, and 48 hours after the first dose, for a total of four doses over three days. After the last dose of Artesunate, patients should switch to oral medicine at least four hours later.
• For patients weighing 20 kilograms or more, the usual dose given through IM or IV injection is 2.4 mg/kg of body weight initially, followed by the same dose at 12 hours, 24 hours, and 48 hours after the first dose, also totaling four doses over three days. After the last dose of Artesunate, patients should transition to oral medicine at least four hours later.

Artesunate Pregnancy Risk Factor: B

• Some animal studies have shown potential risks during pregnancy, but research on pregnant women hasn't indicated a higher chance of birth defects (Kovacs 2015, McGready 1998, McGready 2008).
• Malaria can be more dangerous for pregnant women than for others, potentially leading to severe illness, birth complications, or even death for both the mother and the baby.
• To prevent malaria, pregnant women traveling to areas where it's common should take steps to avoid mosquito bites.
• If they develop severe malaria, doctors may recommend using Artesunate for treatment (Kovacs 2015).

Artesunate use during breastfeeding:

• Small amounts of the active form of artesunate, called dihydroartemisinin, can be found in breast milk, but it's unlikely to cause any harm to nursing infants.
• There haven't been reports of adverse effects on babies from this exposure.
• So, mothers can generally continue breastfeeding while using artesunate without worrying about negative effects on their babies.

Artesunate dose in kidney disease:

• In cases of kidney impairment, no adjustments to the dosage of artesunate are typically needed according to Rosenthal's findings from 2008.
• However, caution should still be exercised, as advised by the World Health Organization in 2015.

Artesunate dose in liver disease:

• According to Rosenthal's research from 2008, no adjustments to the dosage of artesunate are typically required for individuals with liver impairment.
• However, it's important to use the medication cautiously, as recommended by the World Health Organization in 2015.

Side effects of artesunate:

• Cardiovascular:
  • Hypotension
• Central nervous system:
  • Anxiety
  • Ataxia
  • Dizziness
  • Headache
  • Hyperreflexia
  • Metallic taste
  • Restlessness
  • Slurred speech
• Dermatologic:
  • Erythema
  • Pruritus
  • Skin rash
  • Urticaria
• Endocrine & metabolic:
  • Hypoglycemia
• Gastrointestinal:
  • Anorexia
  • Diarrhea
  • Nausea
  • Vomiting
• Hematologic & oncologic:
  • Anemia
  • Hemolysis
  • Neutropenia
  • Reticulocytopenia
• Hepatic:
  • Increased serum ALT
• Hypersensitivity:
  • Angioedema
  • Hypersensitivity reaction
• Neuromuscular & skeletal:
  • Tremor
• Renal:
  • Increased blood urea nitrogen
• Respiratory:
  • Dyspnea

Contraindication to Artesunate Include:

• If someone has a hypersensitivity or allergic reaction to artesunate or any ingredient in the medication, it's important not to use it.
• This information was highlighted in a study by Hess in 2010.

Warnings and Precautions

Hemolysis

• After taking artesunate, a condition called Postartemisinin Delayed Hemolysis (PADH) might occur, usually 1 to 3 weeks later, especially in patients with high levels of malaria parasites.
• This condition involves a decrease in hemoglobin due to the destruction of red blood cells, known as hemolysis.
• The hemoglobin levels typically drop in the second and third weeks after treatment.
• This hemolysis is believed to happen because some infected red blood cells, which were not cleared during artesunate treatment, continue to circulate and then get removed later.
• Acute kidney injury might also be linked to PADH.
• Therefore, it's essential to monitor hemoglobin and kidney function for about a month after using artesunate to watch out for signs of PADH, according to CDC and studies by Jaureguiberry in 2014 and Plewes in 2015.

Hypersensitivity

• Severe allergic reactions, such as angioedema, difficulty breathing, skin redness (erythema), or even anaphylaxis, have been reported with oral administration of artesunate, as noted in a study by Leonardi in 2001.
• It's crucial to watch for signs of hypersensitivity in patients taking artesunate and to stop treatment immediately if severe allergic reactions occur.
• This includes carefully monitoring for any symptoms of allergic reactions and being prepared to discontinue the medication if necessary to prevent serious complications.

QT prolongation:

• While other drugs in the artemisinin class, like artemether, have been linked to QT prolongation (an abnormal heart rhythm), a report by Maude in 2009 suggests that artesunate may not have the same effect.
• This study found that the average QTc interval, which measures heart rhythm, remained unchanged with artesunate use.
• However, caution should still be exercised, especially in patients with pre-existing heart conditions or those taking medications known to prolong the QT interval.

Artesunate (United States: Available via CDC drug service investigational drug [IND] protocol only): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• CBC for hemolysis
• Monitor for resolution of symptoms.

How to administer Artesunate?

Administration for Adults:

• Intravenous (IV): Administer slowly over 1 to 2 minutes through a special filter.
• Intramuscular (IM): Inject into the front of the thigh.

Administration for Children:

• Intramuscular (IM): Inject into the front of the thigh.
• Intravenous (IV): Administer slowly over 1 to 2 minutes through a special filter.

Mechanism of action of Artesunate:

• Artesunate, a medicine derived from artemisinin, acts as a prodrug, converting into dihydroartemisinin (DHA) in the body.
• DHA is effective against all stages of malaria parasites, including gametocytes, and works by disrupting parasite metabolism and helping the body clear infected red blood cells.
• Its antiparasitic action is thought to involve breaking down the parasite's structure, which creates harmful free radicals and damages essential proteins.
• Additionally, DHA might interfere with a cellular enzyme called calcium adenosine triphosphatase (cATP), disrupting parasite protein processing.

Distribution:

• In adults with severe malaria, the volume of distribution (V) for Artesunate is about 15.2 liters per kilogram of body weight, with a range from 2.2 to 39 liters per kilogram.
• For its active metabolite, Dihydroartemisinin (DHA), the volume of distribution is approximately 1.9 liters per kilogram, with a range from 0.8 to 11.5 liters per kilogram. This information comes from a study by Newton in 2006.

Protein Binding:

• Dihydroartemisinin (DHA) is highly bound to proteins in the blood, with about 93% binding, according to the World Health Organization in 2015.

Metabolism:

• Artesunate, being a prodrug, is rapidly converted into its active form, Dihydroartemisinin (DHA), by enzymes in the blood called plasma esterases.
• DHA then undergoes further metabolism in the liver with the help of enzymes like CYP2B6, CYP2C19, and CYP3A4, eventually forming inactive metabolites. This process was discussed in a study by Hess in 2010.

Half-life Elimination:

• The half-life of elimination, which indicates how long it takes for half of the drug to be removed from the body, is short for both Artesunate and Dihydroartemisinin (DHA).
• For Artesunate in adults with severe malaria, the half-life is approximately 0.22 hours, with a range from 0.08 to 0.61 hours. For DHA, the half-life is about 0.34 hours, with a range from 0.14 to 0.87 hours. This data comes from a study by Newton in 2006.

Time to Peak:

• Dihydroartemisinin (DHA) reaches its peak concentration in the blood very quickly. In adults with severe malaria, it usually reaches peak levels within 15 minutes after administration, according to research by Newton in 2006.

Excretion:

• DHA and its metabolites are mainly excreted through urine in the form of DHA-glucuronide, as mentioned by the World Health Organization in 2015.

Artesunate brand names (International):

• A-Keftal
• Absunate
• Altinate
• Arinet
• Artecap
• Artemax
• Artesun
• Artex
• Falciat
• Falcigo
• Junate
• Lykavir
• Malari
• Plasmotrim
• Spy
• Zesunate

Artesunate brand names in Pakistan: