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
Hatton CSR, Peto TEA, Bunch C, et al. Frequency of severe
neutropenia associated with amodiaquine prophylaxis against
malaria. Lancet 1986;I:411-4.
Lepeu G, Codine P, Janbon F, Bertrand A. Agranulocytose a
l'amodiaquine. Nov Presse Med 1981;10:2827-8.
Booth K, Larkin K, Maddocks I. Agranulocytosis coincident with
amodiaquine therapy. Br Med J 1967;3:32-3.
World Health Organization. Vaccination certificate
requirements
and health advice for international travel. 1986;46-8.
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.
Olsen VV, Loft S, Christensen KD. Serious reactions during
malaria prophylaxis with pyrimethamine-sulfadoxine. Lancet
1982;II:994.
CDC. Revised recommendations for preventing malaria in
travelers
to areas with chloroquine-resistant Plasmodium_falciparum.
MMWR
1985;34:185-90.
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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