II. Indications: Severe Malaria (Intravenous Artesunate)
- Malaria confirmation by microscopy (may be waived in some cases by CDC clinician) AND
- One of the following criteria (or inability to take oral medications despite Antiemetics)
- High Parasite density (>5%)
- Altered Level of Consciousness
- Seizures
- Hemodynamic instability or shock
- Acute Respiratory Distress Syndrome (ARDS)
- Pulmonary Edema
- Acidosis
- Acute Kidney Injury
- Disseminated Intravascular Coagulation (ARDS) or other Abnormal Bleeding
- Jaundice AND one other of the criteria
- Severe Anemia (Hemoglobin <7 g/dl)
III. Mechanism
- Artesunate is the only FDA approved injectable drug for Severe Malaria in the U.S.
- Artesunate is a semisynthetic derivative of Artemisinin
- Artemisinin is isolated from the plant Artemisia annua
- Artesunate (AS) is rapidly metabolized to its active metabolite, Dihydroartemisinin (DHA)
- Both AS and DHA are active against blood stage Plasmodium, clearing Parasitemia within 2-3 days
- Slower clearance reported in some regions of Southeast Asia (Cambodia, Thailand, Laos and Vietnam)
IV. Medications: Intravenous Artesunate
- Available in 110 mg single-dose vials
- Available from CDC (if not commercially available)
- Contact CDC Malaria Hotline
V. Dosing: Severe Malaria
- Dosing is the same for children and adults
- Start 2.4 mg/kg IV at 0, 12 and 24 hours
- Next 2.4 mg/kg IV daily of up to 7 days (until Parasite density <1%)
- Next, initiate a complete oral treatment course with other antimalarial
VI. Pharmacokinetics
- Metabolism
- Artesunate (AS): Blood esterases rapidly metabolize to DHA, an active metabolite
- Dihydroartemisinin (DHA): Glucuronidation
- Excretion
- Urine
-
Half-Life
- Artesunate (AS): 0.3 hours
- Dihydroartemisinin (DHA): 1.3 hours
VII. Adverse Effects: In Malaria Patients
- Acute Renal Failure (requiring Hemodialysis)
- Hemoglobinuria
- Anemia
- Jaundice
- Seizure
- Respiratory Failure
- Hypersensitivity (1 in 3000)
VIII. Safety
- Limited safety data in pregnancy
- No reports of major birth defects or adverse maternal or fetal outcomes
- Considered safe in second and third trimesters (and likely safe in first trimester)
- Unknown safety in Lactation
- DHA is detected in Breast Milk
IX. Drug Interactions
- Drugs that decrease Artesunate levels (or DHA)
- Ritonavir
- Nevirapine
- Rifampin (strong UGT Inducer)
- Carbamazepine (strong UGT Inducer)
- Drugs that increase Artesunate levels (or DHA)
- Imatinib (strong UGT Inhibitor)
- Diclofenac (strong UGT Inhibitor)
X. Efficacy: Severe Malaria
- Artesunate (and other Artemisinin derivatives) are preferred for severe Malaria
- Reduced morbidity and mortality
- Artesunate does not prevent relapse of dormant Plasmodium Vivax and Ovale
XI. Resources
- Artesunate (FDA Access Data)
XII. References
- (2020) IV Artesunate for Severe Malaria, Med Lett Drugs Ther, p. 121-3
- Lovecchio (2021) Crit Dec Emerg Med 35(11): 26