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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

  1. White NJ, Looareesuwan S, Warrell DA, Chongsuphajaisiddhi T, Bunnag D, Harinasuta T. Quinidine in falciparum malaria. Lancet 1981;II:1069-71.

  2. 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.

  3. Swerdlow CD, Yu JO, Jacobson E, et al. Safety and efficacy of intravenous quinidine. Am J Med 1983;75:36-42.

  4. 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.

  5. 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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