Intravenous Quinidine Gluconate in the Treatment of Severe
Plasmodium falciparum Infections
Because of its rapid schizontocidal action, quinine has been
the
drug of choice in treating severe Plasmodium falciparum infections.
While quinine sulfate for oral use is readily available in the
United
States, oral therapy is often not practical for patients with
severe
infections from high parasite densities complicated by
gastrointestinal upset, an abnormal sensorium, or endotracheal
intubation. Quinine dihydrochloride for intravenous use, the
usually
recommended drug for such infections, is no longer commercially
available in the United States because of extremely limited demand.
Rather, it must be shipped from CDC, which can lead to delays in
the
institution of therapy that may adversely affect the outcome.
Recent studies from Thailand, where there is renewed interest
in
the use of quinidine as an antimalarial because of increasing
insensitivity to quinine, have shown both oral and intravenous
quinidine to be as effective as quinine in clearing parasitemia
(1,2). In 14 patients with severe P. falciparum infections treated
with intravenous quinidine gluconate, toxicity was limited to
electrocardiographic effects in all patients (QT interval
prolongation, QRS complex widening, and T-wave flattening) without
dysrhythmia; hypotension occurred in two patients who responded to
saline infusion and temporary discontinuation of the drug. The
safety
of intravenous quinidine gluconate when appropriately administered
under closely monitored conditions has been further demonstrated in
patients with heart disease undergoing electrophysiologic study and
in
healthy normal volunteers (3-5).
Quinidine gluconate is an attractive alternative to quinine
dihydrochloride in the treatment of P. falciparum infections when
intravenous therapy is indicated because of its ready availability
in
most U.S. acute-care facilities. Because it is an unlabeled use of
the drug, the Malaria Branch, Division of Parasitic Diseases,
Center
for Infectious Diseases, CDC, has filed an Investigational New Drug
notice (IND) with the U.S. Food and Drug Administration for the
treatment of severe P. falciparum malaria with intravenous
quinidine
gluconate. The protocol involves a trial of treating patients with
high-density parasitemia or any evidence of cerebral malaria, with
continuous infusion quinidine gluconate under closely monitored
conditions in an intensive-care setting.
Physicians who treat patients with such infections are
encouraged
to contact CDC's Malaria Branch (telephone (404) 452-4046 weekdays;
(404) 329-2888 evenings, weekends, and holidays) for protocol
instructions, including dose recommendations, evaluation
procedures,
and reporting requirements. It is hoped that information collected
from such patients will corroborate the encouraging experience in
Thailand and establish quinidine gluconate as a safe and effective
antimalarial when used in acute-care facilities in the United
States.
Reported by Malaria Br, Div of Parasitic Diseases, Center for
Infectious Diseases, CDC.
References
White NJ, Looareesuwan S, Warrell DA, Chongsuphajaisiddhi T,
Bunnag D, Harinasuta T. Quinidine in falciparum malaria.
Lancet
1981;II:1069-71.
Phillips RE, Warrell DA, White NJ, Looareesuwan S, Karbwang J.
Intravenous quinidine for the treatment of severe falciparum
malaria: clinical and pharmacokinetic studies. N Engl J Med
1985;312:1273-8.
Swerdlow CD, Yu JO, Jacobson E, et al. Safety and efficacy of
intravenous quinidine. Am J Med 1983;75:36-42.
Ochs HR, Grube E, Greenblatt DJ, Woo E, Bodem G. Intravenous
quinidine: pharmacokinetic properties and effects on left
ventricular performance in humans. Am Heart J 1980;99:468-75.
Greenblatt DJ, Pfeifer HJ, Ochs HR, et al. Pharmacokinetics of
quinidine in humans after intravenous, intramuscular and oral
administration. J Pharmacol Exp Ther 1977;202:365-78.
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