II. Indications: Severe Malaria (Intravenous Artesunate)

  1. Malaria confirmation by microscopy (may be waived in some cases by CDC clinician) AND
  2. One of the following criteria (or inability to take oral medications despite Antiemetics)
    1. High Parasite density (>5%)
    2. Altered Level of Consciousness
    3. Seizures
    4. Hemodynamic instability or shock
    5. Acute Respiratory Distress Syndrome (ARDS)
    6. Pulmonary Edema
    7. Acidosis
    8. Acute Kidney Injury
    9. Disseminated Intravascular Coagulation (ARDS) or other Abnormal Bleeding
    10. Jaundice AND one other of the criteria
    11. Severe Anemia (Hemoglobin <7 g/dl)

III. Mechanism

  1. Artesunate is the only FDA approved injectable drug for Severe Malaria in the U.S.
  2. Artesunate is a semisynthetic derivative of Artemisinin
    1. Artemisinin is isolated from the plant Artemisia annua
  3. Artesunate (AS) is rapidly metabolized to its active metabolite, Dihydroartemisinin (DHA)
    1. Both AS and DHA are active against blood stage Plasmodium, clearing Parasitemia within 2-3 days
    2. Slower clearance reported in some regions of Southeast Asia (Cambodia, Thailand, Laos and Vietnam)

IV. Medications: Intravenous Artesunate

  1. Available in 110 mg single-dose vials
  2. Available from CDC (if not commercially available)
  3. Contact CDC Malaria Hotline
    1. https://www.cdc.gov/media/releases/2019/s0328-artesunate-first-line-treatment.html

V. Dosing: Severe Malaria

  1. Dosing is the same for children and adults
  2. Start 2.4 mg/kg IV at 0, 12 and 24 hours
  3. Next 2.4 mg/kg IV daily of up to 7 days (until Parasite density <1%)
  4. Next, initiate a complete oral treatment course with other antimalarial

VI. Pharmacokinetics

  1. Metabolism
    1. Artesunate (AS): Blood esterases rapidly metabolize to DHA, an active metabolite
    2. Dihydroartemisinin (DHA): Glucuronidation
  2. Excretion
    1. Urine
  3. Half-Life
    1. Artesunate (AS): 0.3 hours
    2. Dihydroartemisinin (DHA): 1.3 hours

VII. Adverse Effects: In Malaria Patients

VIII. Safety

  1. Limited safety data in pregnancy
    1. No reports of major birth defects or adverse maternal or fetal outcomes
    2. Considered safe in second and third trimesters (and likely safe in first trimester)
  2. Unknown safety in Lactation
    1. DHA is detected in Breast Milk

IX. Drug Interactions

  1. Drugs that decrease Artesunate levels (or DHA)
    1. Ritonavir
    2. Nevirapine
    3. Rifampin (strong UGT Inducer)
    4. Carbamazepine (strong UGT Inducer)
  2. Drugs that increase Artesunate levels (or DHA)
    1. Imatinib (strong UGT Inhibitor)
    2. Diclofenac (strong UGT Inhibitor)

X. Efficacy: Severe Malaria

  1. Artesunate (and other Artemisinin derivatives) are preferred for severe Malaria
    1. Reduced morbidity and mortality
  2. Artesunate does not prevent relapse of dormant Plasmodium Vivax and Ovale

XII. References

  1. (2020) IV Artesunate for Severe Malaria, Med Lett Drugs Ther, p. 121-3
  2. Lovecchio (2021) Crit Dec Emerg Med 35(11): 26

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