Notice to Readers: Availability and Use of Parenteral Quinidine
Gluconate for Severe or Complicated Malaria
Since 1991, quinidine gluconate, a class 1a anti-arrhythmic agent, has been the
only parenteral antimalarial available for use in the United States
(1). It is indicated for the treatment of patients with life-threatening
Plasmodium falciparum malaria (2),
including those who cannot tolerate oral therapy, have high-grade parasitemia, or have
complications (e.g., cerebral malaria or acute renal failure)
(3,4).
The limited availability of and delays in obtaining quinidine gluconate have
contributed to adverse patient outcomes
(5--7). As newer anti-arrhythmics have
replaced quinidine for many cardiac indications, some hospitals and other health-care
facilities have dropped quinidine gluconate from their formularies and, as a result, fewer
clinicians have had experience using the drug. Discussions among quinidine gluconate
manufacturer Eli Lilly Company (Indianapolis, Indiana), CDC, the U.S. Department of Defense,
and the U.S. Food and Drug Administration have resulted in the following
recommendations to improve quinidine gluconate availability for acutely ill malaria patients in U.S.
health-care facilities:
Before an acute need arises, hospital drug services should consider
maintaining or adding quinidine gluconate to formularies or should be able to
immediately locate a nearby source.
Pharmacists and clinicians requiring quinidine gluconate in hospitals in which
an immediate source cannot be located should contact their local or regional
distributor to request quinidine gluconate.
In clinical settings in which the need for the drug is more acute than can be met
by the local or regional distributor, pharmacists and clinicians should contact Eli
Lilly Company, telephone, (800) 821-0538 to arrange a rapid shipment of the
drug. This telephone number, or an alternate number given to callers, is staffed
24 hours a day, 7 days a week.
If further assistance is needed in obtaining quinidine gluconate or in
managing patients with malaria, contact CDC's malaria hotline, (770) 488-7788
(Monday--Friday, 8 a.m. to 4:30 p.m. eastern standard time). After business hours,
weekends, and holidays, contact CDC's security station, telephone, (404) 639-2888
and ask to have the on-call person for malaria questions paged.
The following dosing recommendations for quinidine gluconate administration
are provided for pharmacists and clinicians treating patients with severe or
complicated malaria:
Quinidine gluconate intravenous should be administered in a monitored
setting. Prolongation of the QT interval as indicated by an electrocardiogram,
ventricular arrhythmia, hypotension, and hypoglycemia can result from the use of this
drug at treatment doses.
Quinidine gluconate for malaria is administered as an initial intravenous
loading dose of 10 mg/kg salt (equivalent to 6.25 mg/kg quinidine base) infused over
1--2 hours. Quinidine gluconate is administered subsequently as a continuous
infusion of 20 µg/kg/min quinidine gluconate salt (equivalent to 12.5 µg/kg/min
quinidine base) (2).
An alternative regimen is an intravenous loading dose of 24 mg/kg quinidine
salt (equivalent to 15 mg/kg quinidine base) infused over 4 hours, followed by
a maintenance infusion of 12 mg/kg of quinidine gluconate salt (equivalent
to 7.5 mg/kg quinidine base) infused over 4 hours every 8 hours, starting 8 hours
after the loading dose (2). These regimens have been shown to be effective with
or without concomitant exchange transfusion
(2).
The risk for serious ventricular arrhythmia associated with quinidine is
increased by bradycardia, hypokalemia, and hypomagnesemia
(2). When determining whether a patient should receive a bolus dose, previous administration of
other drugs that can prolong the QT interval (e.g., quinine, halofantrine, and
mefloquine) should be considered.
No alternatives to quinidine exist for patients in the United States who
require intravenous therapy for malaria. Acute cardiac events can be minimized by
careful calculation of the loading dose and infusion rate. Consulting a cardiologist
may be helpful when attempting to resume infusion in the patient who has
experienced QT prolongation or hypotension associated with intravenous
quinidine infusion.
Consulting a physician with experience in treating malaria is advised.
References
CDC. Treatment with quinidine gluconate of persons with severe
Plasmodium falciparum infection: discontinuation of parenteral quinine from CDC drug service. MMWR
1991;40(no. RR-4):21--3.
Quinidine gluconate injection [package insert]. Indianapolis, Indiana: Eli Lilly
Company, February 2000.
Zucker JR, Campbell CC. Malaria: principles of prevention and treatment. Infect Dis Clin
No Am 1993;7:547--67.
Miller KD, Greenberg AE, Campbell CC. Treatment of severe malaria in the United
States with a continuous infusion of quinidine gluconate and exchange transfusion. N Engl
J Med 1989;321:65--70.
Rosenthal PJ, Petersen C, Geertsma FR, et al. Availability of intravenous quinidine
for falciparum malaria [Letter]. N Engl J Med 1996;335:138.
Humar A, Sharma S, Zoutman D, et al. Fatal falciparum malaria in Canadian travelers.
Can Med Assoc J 1997;156:1165--7.
CDC. Availability of parenteral quinidine gluconate for treatment of severe or
complicated malaria. MMWR 1996;45:494--5.
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