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International Notes Agranulocytosis Associated with the Use of Amodiaquine for Malaria Prophylaxis

Seven cases of agranulocytosis associated with the use of amodiaquine (Camoquine) among British travelers have recently been reported (1). Sixteen additional cases of agranulocytosis from Western Europe associated with the use of amodiaquine have recently been reported to the drug manufacturer, and two U.S. cases have been reported to CDC. Twenty-three of these 25 cases occurred in 1985 or 1986, and seven are reported to have been fatal. Among 20 cases for which the duration of amodiaquine prophylaxis is known, usage ranged from 3 weeks to 24 weeks. In all but four of the 25 cases, amodiaquine was used at the appropriate dosage (adults 400 mg base per week) for prophylaxis. Fourteen of the patients are known to have used another antimalarial drug concurrently for prophylaxis; weekly pyrimethamine-sulfadoxine (Fansidar) was used in five cases, and daily proguanil (Paludrine), in nine cases. Reported by Malaria Br, Div of Parasitic Diseases, Center for Infectious Diseases, Div of Quarantine, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: Amodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as both an antimalarial and an anti-inflammatory agent for more than 30 years. Only rarely has amodiaquine been associated with agranulocytosis: of 13 reports published between 1955 and 1985, only three were associated with the use of amodiaquine at recommended dosages for malaria prophylaxis in the absence of the use of other drugs known to have similar toxicity (2,3).

The reason for the discrepancy between the previous and recent experiences with amodiaquine is not clear. While previously used largely for treating malaria in endemic areas, amodiaquine has been increasingly recommended for chemoprophylaxis in nonimmune visitors to endemic areas (4,5). It is not known whether bone-marrow toxicity is more likely to occur when the drug is used on a routine weekly basis for prophylaxis or when used in combination with other antimalarials, such as Fansidar or Paludrine. Agranulocytosis has been associated with the use of Fansidar alone (6), but has not been reported when Paludrine has been used alone.

Alternatively, the recent increase in the number of agranulocytosis cases might be explained by an increase in the number of persons using amodiaquine for malaria prophylaxis. Although amodiaquine is not marketed in the United States, information provided by the manufacturer indicates that the number of Europeans using amodiaquine for malaria prophylaxis may have increased in 1985. In the United Kingdom, amodiaquine became available in March 1985 after a 10-year hiatus in marketing; in Switzerland, a threefold increase in amodiaquine sales was noted from 1984 to 1985.

In April 1985, CDC revised its recommendations for preventing malaria in travelers, because of severe cutaneous reactions associated with the use of Fansidar, and recommended amodiaquine use for malaria prophylaxis could be considered as an alternative for longer-term travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum (CRPF) (7). This recommendation was based on studies showing amodiaquine was somewhat more effective than chloroquine in treating CRPF infections (8) and, therefore, might provide more protection than chloroquine when used as weekly prophylaxis in areas where CRPF transmission occurs. Similarly, the World Health Organization recently suggested the use of amodiaquine as an alternative to chloroquine and recommended that it be used in combination with Paludrine or Maloprim (dapsone-pyrimethamine) for travel to certain areas (4).

It is now apparent that any possible prophylactic advantage that amodiaquine may afford is not justified by the possible risk of agranulocytosis associated with the use of the drug. CDC, therefore, no longer recommends that amodiaquine be used for prophylaxis. Otherwise, previous recommendations for the prevention of malaria in travelers remain valid (5,7).

References

  1. Hatton CSR, Peto TEA, Bunch C, et al. Frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria. Lancet 1986;I:411-4.

  2. Lepeu G, Codine P, Janbon F, Bertrand A. Agranulocytose a l'amodiaquine. Nov Presse Med 1981;10:2827-8.

  3. Booth K, Larkin K, Maddocks I. Agranulocytosis coincident with amodiaquine therapy. Br Med J 1967;3:32-3.

  4. World Health Organization. Vaccination certificate requirements and health advice for international travel. 1986;46-8.

  5. CDC. Health information for international travel, 1985. Atlanta, Georgia: U.S. Public Health Service, Department of Health and Human Services, 1985; CDC publication no. 85-8280;73-82.

  6. Olsen VV, Loft S, Christensen KD. Serious reactions during malaria prophylaxis with pyrimethamine-sulfadoxine. Lancet 1982;II:994.

  7. CDC. Revised recommendations for preventing malaria in travelers to areas with chloroquine-resistant Plasmodium_falciparum. MMWR 1985;34:185-90.

  8. Watkins WM, Sixsmith DG, Spencer HC, et al. Effectiveness of amodiaquine as treatment for chloroquine-resistant Plasmodium_ falciparum infections in Kenya. Lancet 1984;I:357-9.



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