The Committee reviewed the re-application for the inclusion of amo-diaquine, an antimalarial, having deferred a decision regarding this medicine at its previous meeting (2). Amodiaquine has been on the Model List since 1977 (3), was removed in 1979 (12), reinstated in 1982 (13) and removed again in 1988 (14) in view of safety concerns in prophylactic use. In 2002, the Committee reviewed an application for its inclusion for therapeutic use. At that time, the Committee concluded that as amodiaquine had been removed twice for safety reasons, a careful review of the safety information was needed before any decision about its future inclusion could be taken. The Committee had also noted with concern the results of a trial of amodiaquine in children that appeared to show a high rate of neutropenia (2).

The Committee noted the information supplied with the reapplication, which included a systematic review of adverse events (prepared by the Cochrane Infectious Diseases Group) and a review of the effects of amodiaquine treatment on white blood cell and neutrophil counts (presented by Roll Back Malaria, WHO). The Committee agreed that antimalarial drug treatment with amodi-aquine (either alone or in combination with sulfadoxine + py-rimethamine or artesunate), chloroquine and sulfadoxine + pyrimethamine may be associated with a decline in the total white cell and neutrophil counts. Although both counts remained within the normal range in the majority of cases, a small proportion of patients were found to have developed neutropenia when assessed during follow-up. The clinical significance of this finding is, however, unknown. Other publications reviewed by the Committee suggest that peripheral neutropenia is a part of the natural course of malaria itself (15, 16).

The Committee concluded that the above findings generally support the conclusions of the systematic review of adverse events submitted by the Cochrane Infectious Diseases Group namely that, relative to other commonly used antimalarial drugs, therapeutic use of amodi-aquine does not appear to be associated with an increased risk of neutropenia. The Committee therefore recommended that amodiaquine (as tablets, 153mg, 200mg (base)) be added to the Model List as a core list medicine, with the following footnote:

Amodiaquine should preferably be used as part of combination therapy.

and that the following text be added at the beginning of the relevant section of the Model List, i.e. section 6.5.3(a):

Medicines for the treatment of P. falciparum malaria cases should be used in combination.

The Committee also recommended that amodiquine's place in curative treatment be further defined by WHO guidelines and expressed an interest in reviewing the results of more clinical trials on the comparative efficacy and safety of fixed-dose combinations in the treatment of malaria.