title: Intravenous Artesunate for the Treatment of Severe and Complicated Malaria in the United States: Clinical Use Under an Investigational New Drug Protocol.
abstract: BACKGROUND
  Quinidine gluconate, the only U.S. Food and Drug Administration-approved treatment for life-threatening malaria in the United States, has a problematic safety profile and is often unavailable in hospitals.
  
  
  OBJECTIVE
  To assess the safety and clinical benefit of intravenous artesunate as an alternative to quinidine.
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  U.S. hospitals.
  
  
  METHODS
  102 patients aged 1 to 72 years (90% adults; 61% men) with severe and complicated malaria. Patients received 4 weight-based doses of intravenous artesunate (2.4 mg/kg) under a treatment protocol implemented by the Centers for Disease Control and Prevention between January 2007 and December 2010. At baseline, 35% had evidence of cerebral malaria, and 17% had severe hepatic impairment. Eligibility required the presence of microscopically confirmed malaria, need for intravenous treatment, and an impediment to quinidine.
  
  
  METHODS
  Clinical and laboratory data from each patient's hospital records were abstracted retrospectively, including information from baseline through a maximum 7-day follow-up, and presented before a physician committee to evaluate safety and clinical benefit outcomes.
  
  
  RESULTS
  7 patients died (mortality rate, 6.9%). The most frequent adverse events were anemia (65%) and elevated hepatic enzyme levels (49%). All deaths and most adverse events were attributed to the severity of malaria. Patients' symptoms generally improved or resolved within 3 days, and the median time to discharge from the intensive care unit was 4 days, even for patients with severe liver disease or cerebral malaria. More than 100 concomitant medications were used, with no documented drug-drug interactions.
  
  
  CONCLUSIONS
  Potential late-presenting safety issues might occur outside the 7-day follow-up.
  
  
  CONCLUSIONS
  Artesunate was a safe and clinically beneficial alternative to quinidine.
authors: Patrick S
authors: PS
authors: Twomey
authors: Bryan L
authors: BL
authors: Smith
authors: Cathy
authors: C
authors: McDermott
authors: Anne
authors: A
authors: Novitt-Moreno
authors: William
authors: W
authors: McCarthy
authors: S Patrick
authors: SP
authors: Kachur
authors: Paul M
authors: PM
authors: Arguin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008288:Malaria / Q000150:complications / Q000188:drug therapy*; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D018512:Parasitemia / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D015507:Drugs, Investigational; D000077332:Artesunate