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

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.