On June 21, 2007, CDC's Investigational New Drug Application (IND) for intravenous artesunate went into effect. This IND allows for use of an investigational antimalarial medication (intravenous artesunate) under a protocol entitled “Intravenous Artesunate for Treatment of Severe Malaria in the United States.” Intravenous artesunate can be used only under the provisions of this IND protocol because it is not a drug approved by the Food and Drug Administration (FDA). Artesunate is in the class of medications known as artemisinins, which are derivatives from “quing hao,” or sweet wormwood plant (Artemisia annua). Only the CDC Drug Service and CDC Quarantine Stations will be permitted to release the medication for use under this IND protocol.
Approximately 1,400 cases of malaria (nearly all imported) are diagnosed in the United States each year; approximately 10% are cases of severe malaria.1 Intravenous quinidine gluconate, principally used as an antiarrhythmic medicine, also has antimalarial properties and is the only parenteral drug approved by FDA for treatment of severe malaria that is available in the United States. However, quinidine has cardiotoxic effects and has become less available in U.S. hospitals with the advent of newer antiarrhythmic drugs.2,3 Since 2000, the World Health Organization has recommended artesunate in preference to quinidine for treatment of severe malaria, and artesunate has been used outside the United States for many years.4 CDC's IND protocol provides a mechanism for investigational use of intravenous artesunate for patients with severe malaria in the United States.
The Walter Reed Army Institute for Research has agreed to provide a supply of intravenous artesunate to CDC for release to hospitals in the United States under the IND protocol for treatment of patients with severe malaria. To be eligible to receive intravenous artesunate under CDC's IND protocol, patients must have malaria and need parenteral therapy because they are either unable to take oral medications, have high-density parasitemia (>5%), or have severe malaria, indicated by other clinical criteria such as acute respiratory distress syndrome or severe anemia. In addition, for these patients, one of the following must be true: (1) artesunate is available more rapidly than quinidine (if the drugs are equally available, attending clinicians will decide which drug to use in consultation with CDC), (2) the patient has experienced quinidine failure or intolerance, or (3) use of quinidine is contraindicated.
Under the IND protocol, intravenous artesunate should be administered in 4 equal doses of 2.4 mg/kg each over a 3-day period. In parts of the world where artesunate is used regularly, intravenous administration typically is followed by a course of oral antimalarial medication once the patient is able to tolerate medications by mouth. Although artesunate is a life-saving drug, it has a short half-life, and supplementary therapy is necessary to increase the likelihood of eliminating all of the circulating parasites. This is similar to the current standard of care regimens in the United States, in which a rapidly acting drug such as quinine or quinidine is always coupled with a follow-on drug such as doxycycline or clindamycin. The recommended options for follow-on drugs in this protocol are oral treatment with atovaquone-proguanil (Malarone®), doxycycline, clindamycin, or mefloquine.
Artesunate will be provided free to hospitals, upon request and on an emergency basis, by the CDC Drug Service or by one of the CDC Quarantine Stations. Physicians who administer the drug to patients must notify CDC of any adverse event after administration and comply with the IND protocol. To enroll a patient with severe malaria in this treatment protocol, health-care providers should telephone the CDC Malaria Hotline at 770-488-7788, Monday–Friday, 8 a.m.–4:30 p.m., Eastern time. At other times, callers should telephone 770-488-7100 and ask to speak with a CDC Malaria Branch clinician.
Notice to Readers: New Medication for Severe Malaria Available Under an Investigational New Drug Protocol. JAMA. 2007;298(10):1156. doi:10.1001/jama.298.10.1156