IDStewardship

Artesunate

Artesunate key points and resources.

KEY POINTS

  • Artesunate has direct antimalarial activity but is also rapidly metabolized into the metabolite dihydroartemisinin (DHA) which also has antimalarial activity. Both artesunate and DHA are artemisinin drugs. They contain an endoperoxide bridge that is activated by heme iron, which leads to oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and a decrease in parasite growth/survival.
    • Is active against the different asexual forms of Plasmodium parasites
    • Is produced by Amivas and there appears to be no brand name
  • FDA-approved May 26th, 2020 to treat severe malaria in adult and pediatric patients
    • Use of artesunate should be followed by a complete oral treatment course of an appropriate antimalarial regimen
    • Previously available for years in the U.S. through the FDA’s Expanded Access program
      • Had allowed CDC to provide IV artesunate through an investigational new drug protocol
    • Currently the only drug on the US market to treat severe malaria
  • Clinical data have demonstrated artesunate to be associated with improved mortality as compared to quinine when treating hospitalized patients with severe malaria
  • Does not treat the hypnozoite liver stage form of Plasmodium (the genus that causes malaria), which means it will not prevent relapses from P. vivax or P. ovale infection
  • Available for intravenous use only, dosed 2.4 mg/kg IV at 0 hours, 12 hours, and 24 hours. Then administer once daily until patients is able to tolerate antimalarial therapy.
    • No renal or hepatic dose adjustments recommended in the package insert
    • Administered via slow bolus over 1-2 minutes
    • Should not be given as a continuous infusion
    • Provided as a 110 mg powder per vial for consititution
      • Provided with the diluent
      • To be used within 1.5 hours of constitution
  • Should clear parasitemia within 48-72 hours
  • Holds warnings for:
    • Post-treatment hemolysis
      • Patients require regular blood tests for the 4-week period following artesunate completion to monitor for this
    • Hypersensitivity reaction
  • Common adverse reactions include acute renal failure requiring dialysis, hemoglobinuria, and jaundice
  • May cause fetal harm, but may be life saving for a pregnant woman and her fetus, requiring a risk:benefit assessment
  • Beware drug-drug interactions with strong UDP-glucuronosyltransferase inducers (e.g., ritonavir) or strong UGT inhibitors (e.g., diclofenac)

RESOURCES

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