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:

• 2.4 mg/kg/dose initially as an intravenous or intramuscular injection.
• The first dose is followed by 2.4 mg/kg/dose at 12 hours, 24 hours, and 48 hours for a total of four doses over a period of three days.
• Severely ill patients and patients who do not tolerate oral therapy may require an additional course of four doses.
• The patients should be switched to oral therapy 4 hours after the last dose.

Artesunate Dose in Childrens

Artesunate Dose in the treatment of Severe Malaria:

• Infants, Children, and Adolescents:

  • Patient weighing less than 20 kgs:

    • 3 mg/kg/dose intramuscular or intravenous initially.
    • This is followed by 3 mg/kg/dose at 12 hours, 24 hours, and 48 hours after the first dose for a total of four doses over 3 days.
    • Patients should be switched to oral therapy 4 hours after the last dose.

  • Patient weighing more than 20 kg:

    • 2.4 mg/kg/dose intravenous or intramuscular initially.
    • This is followed by 2.4 mg/kg/dose at 12 hours, 24 hours, and 48 hours after the first dose for a total of four doses over a period of 3 days.
    • Oral therapy should be started 4 hours after the last dose.

Artesunate Pregnancy Risk Factor: B

• While adverse effects in animals have been reported, they have not been seen in humans.
• Malaria caused by Falciparum can cause death in pregnant women. It can cause maternal death, fetal death, and congenital malformations.
• Travelers visiting endemic areas should use personal protection and start chemoprophylaxis. It is not used for chemoprophylaxis of malaria.
• Artesunate can be used to treat severe malaria in pregnant women.

Artesunate use during breastfeeding:

• Breastmilk can contain a small amount of it, but adverse events have not been reported.

Artesunate dose in kidney disease:

Adjustment in th dose is not necessary in patients with liver disease.

However, it should be used with caution in patients with severe renal impairment.

Artesunate dose in liver disease:

Adjustment in th dose is not necessary in patients with liver disease. 

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:

• Allergy to artesunate and any component of the formulation

Warnings and Precautions

• Hemolysis

  • Postartemisinin delayed haemolysis (PADH), which can occur after artesunate administration for 1 to 3 weeks, is marked by a decrease in hemoglobin.
  • Patients with high levels of parasitemia are more at risk for hemolysis.
  • Hemolysis is caused by the clearing of infectederythrocytes. The incidence of hemolysis decreases after the third week.
  • Acute kidney injury has been linked to severe hemolysis.
  • After the administration of artesunate, it is important to monitor your hemoglobin and kidney functions for a month.

• Hypersensitivity

  • As severe allergic reactions have been reported after oral administration, patients should be closely monitored.
  • If the patient experiences angioedema or dyspnea, anaphylaxis and erythema, it is best to stop treatment.

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?

Intravenous:

• Administer the artesunate through an intravenous bolus slowly over 1 - 2 minutes.

Intramuscular:

• Administer into the anterior thigh by Intramuscular injection.

Mechanism of action of Artesunate:

• Artesunate, a prodrug, is converted into the active form of dihydroartemisinin.
• It is an antimalarial drug which is active against all erythrocytic malarial infections, including those in the gametocytes.
• It damages parasite proteins through the formation of free radicals by the cleavage Fe of endoperoxide-bridge.
• It also inhibits the calcium adenosine tripophosphate from the sarcoplasmic-endoplasmic reticulum, which impairs the folding of parasite proteins.

93% of the drug's total isprotein-bound. The plasma esterases hydrolyze artesunate to activate it to dihydroartemisinin.

The active compound is then subject to hepatic metabolism via CYP2B6, CYP2C19 and CYP3A4 which leads to inactive metabolites.

The elimination of Half-lifeAdults suffering from severe malaria will need artesunate for 0.22 hours, while the active metabolite takes 0.34 hours.

Time to get therepeak plasma concentrationThe average time it takes to get severe malaria in adults is 15 minutes. It is most common in the tropics.excretedIn the urine.

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: