Intravenous Artesunate for the Treatment of Severe and Complicated Malaria in the United States: Clinical Use Under an Investigational New Drug Protocol

Ann Intern Med. 2015 Oct 6;163(7):498-506. doi: 10.7326/M15-0910.

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.

Design: Retrospective case series.

Setting: U.S. hospitals.

Patients: 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.

Measurements: 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.

Limitation: Potential late-presenting safety issues might occur outside the 7-day follow-up.

Conclusion: Artesunate was a safe and clinically beneficial alternative to quinidine.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimalarials / adverse effects
  • Antimalarials / therapeutic use*
  • Artemisinins / adverse effects
  • Artemisinins / therapeutic use*
  • Artesunate
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / therapeutic use*
  • Female
  • Humans
  • Infant
  • Injections, Intravenous
  • Malaria / complications
  • Malaria / drug therapy*
  • Male
  • Medication Adherence
  • Middle Aged
  • Parasitemia / complications
  • Parasitemia / drug therapy*
  • Retrospective Studies
  • Treatment Outcome
  • United States
  • Young Adult

Substances

  • Antimalarials
  • Artemisinins
  • Drugs, Investigational
  • Artesunate