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11/27/2000

CDC Advises on Use and Availability of Injectable Quinidine Gluconate to Treat Severe or Complicated Malaria

Cheryl A. Thompson

The Centers for Disease Control and Prevention (CDC) offers the following information on the availability and use of injectable quinidine gluconate for treating severe or complicated malaria.

Since 1991, quinidine gluconate, a class 1A antiarrhythmic agent, has been the only injectable antimalarial available for use in the United States.1 The drug is indicated for the treatment of patients with life-threatening Plasmodium falciparum malaria,2 including those for whom oral therapy is not possible, those with high-grade parasitemia, or those with complications such as cerebral malaria or acute renal failure.3,4

In the past decade, there has been a growing problem with the availability of quinidine gluconate. Delays in obtaining this drug have contributed to adverse patient outcomes.5-7 As newer antiarrhythmics have replaced quinidine for many of its cardiac indications, some hospitals and health care facilities have dropped quinidine gluconate from their formularies. Concomitantly, the number of clinicians with experience in using this drug has decreased.

Recent discussion among the manufacturer of quinidine gluconate, CDC, Department of Defense, and Food and Drug Administration to improve availability of the drug to acutely ill malaria patients in health care facilities in the United States has resulted in the following recommendations:

  • Hospital pharmacies should consider the critical role of quinidine gluconate in the treatment of patients with severe malaria when choosing drugs to maintain on or add to the formulary. This decision should occur before the acute need for the drug arises (i.e., either stock the drug product or know which nearby hospitals or other health care facilities stock it).   
  • In hospitals that do not have quinidine gluconate on the formulary, pharmacists who need the drug for patients with severe malaria should first contact the hospital's local or regional drug distributor to request a supply.      
  • In clinical settings that have a more acute need for the drug than the local distributor can meet, pharmacists should contact the manufacturer—Eli Lilly and Company at 800-821-0538—to arrange for rapid shipment of quinidine gluconate directly to the health care site. This toll-free number, or an alternate number to which callers will be directed, is staffed 24 hours a day seven days a week.      
  • If further assistance is needed to obtain a supply of quinidine gluconate (or manage a patient with malaria), call the CDC Malaria Hotline at 770-488-7788 (8:00 a.m. to 4:30 p.m. EST, Monday through Friday). After hours and on weekends and holidays, call the CDC Security Station at 404-639-2888 and ask the operator to page the on-call person who is answering malaria questions.

For the treatment of patients severely ill with malaria, consultation with a physician who has experience in treating the disease is advised. In cases of severe or complicated malaria, adhere to the following dosage recommendations for quinidine gluconate administration:

  • Intravenous (i.v.) quinidine gluconate should be administered in a monitored setting. Prolongation of the QT interval, ventricular arrhythmias, hypotension, and hypoglycemia can result from use of this drug at antimalarial dosages.  
  • For the treatment of malaria, quinidine gluconate is administered as an initial i.v. dose of 10 mg (equivalent to 6.25 mg of quinidine base) per kilogram of body weight over one to two hours. After this loading dose, the drug is administered as a continuous i.v. infusion of 20 mcg/kg/min of quinidine gluconate (equivalent to 12.5 mcg/kg/min of quinidine base).2     
  • An alternative regimen involves an i.v. loading dose of 24 mg of quinidine gluconate (equivalent to 15 mg of quinidine base) per kilogram of body weight infused over four hours, followed by a maintenance dosage of 12 mg/kg of quinidine gluconate (equivalent to 7.5 mg/kg of quinidine base) infused over four hours every eight hours, starting eight hours after the loading dose.2     
  • The risk of serious ventricular arrhythmias from quinidine use is increased by bradycardia, hypokalemia, and hypomagnesemia.2 When determining whether a patient should receive a bolus dose, the clinician should also consider whether the patient has already received a drug—such as quinine, halofantrine, or mefloquine—that might prolong the QT interval.     
  • Both the primary and alternative dosage regimens have been shown to be effective, with or without concomitant exchange transfusion.2     
  • In the United States, there are no alternative i.v. antimalarials to quinidine. Clinicians should carefully calculate the loading dose and infusion rate of quinidine in order to prevent acute cardiac events. Consultation with a cardiologist may be helpful when a quinidine infusion is to be resumed in a patient who has had QT prolongation or hypotension during a previous exposure.
    1. Quinidine gluconate injection package insert. Indianapolis, IN: Eli Lilly and Company; 2000 Feb.
    2. Zucker JR, Campbell CC. Malaria: principles of prevention and treatment. Infect Dis Clin North Am. 1993; 7:547-67.
    3. Miller KD, Greenberg AE, Campbell CC. Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange infusion. N Engl J Med. 1989; 321:65-70.
    4. Rosenthal PJ, Petersen C, Geertsma FR et al. Availability of intravenous quinidine for falciparum malaria. N Engl J Med. 1996; 335:138. Letter.
    5. Humar A, Sharma S, Zoutman D et al. Fatal faciparum malaria in Canadian travelers. Can Med Assoc J. 1997; 156:1165-7.

Except for the details on obtaining an emergency supply of the drug, the above information already appears in the monograph for quinidine gluconate in AHFS DI, ASHP's drug information reference.