Piero L Olliaro, Paola Mussano

Amodiaquine has been widely used to treat malaria. Fatal adverse reactions have been reported in adults taking it for prophylaxis. This has led some authorities to suggest it is withdrawn as a first line treatment for malaria. To compare amodiaquine with chloroquine or sulfadoxine-pyrimethamine for treating uncomplicated Plasmodium falciparum malaria. We searched the Cochrane Infectious Diseases Group specialized trials register (February 2003), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1980 to December 2002), LILACS (February 2003). We contacted researchers in the field and pharmaceutical companies. Randomised and quasi-randomised trials. Two reviewers independently extracted data and assessed trial quality. 56 studies included, mostly from Africa. Treatment allocation was adequately concealed in three trials, and unclear or inadequate in the remainder. Amodiaquine was more effective than chloroquine for parasite clearance (day 7, Peto odds ratio 4.42 (95% confidence interval 3.65 to 5.35); day 14, Peto odds ratio 6.44 (95% confidence interval (CI) 5.09 to 8.15). Comparisons with sulfadoxine/pyrimethamine were more mixed, with sulfadoxine/pyrimethamine more effective on day 28 (Peto odds ratio 0.41; 95% CI 0.28 to 0.61). No significant difference for adverse events was observed between amodiaquine and chloroquine and sulfadoxine/pyrimethamine. Reported adverse effects were minor or moderate. No life threatening events were detected. There is evidence to support the continued use of amodiaquine to treat uncomplicated malaria, although local drug resistance patterns need to be considered. Monitoring for adverse events should continue.