Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: Results from a randomized, double-blind study

Concerns about the tolerability of mefloquine highlight the need for new dr ugs to prevent malaria. Atovaquone-proguanil. (Malarone; GlaxoSmithKline) w as safe and effective for prevention of falciparum malaria in lifelong resi dents of malaria-endemic countries, but experience in nonimmune people is l imited. In a randomized, double-blind study, nonimmune travelers received m alaria prophylaxis with atovaquone-proguanil (493 subjects) or mefloquine ( 483 subjects). Information about adverse events (A-Es) and potential episod es of malaria was obtained 7, 28, and 60 days after travel. AEs were report ed by an equivalent proportion of subjects who had received atovaquone-prog uanil or mefloquine (71.4% versus 67.3%; difference, 4.1%; 95% confidence i nterval, -1.71 to 9.9). Subjects who received atovaquone-proguanil had fewe r treatment-related neuropsychiatric AEs (14% versus 29%; P=.001), fewer AE s of moderate or severe intensity (10% versus 19%; P=.001), and fewer AEs t hat caused prophylaxis to be discontinued (1.2% versus 5.0%; P=.001), compa red with subjects who received melfoquine. No confirmed diagnoses of malari a occurred in either group. Atovaquone-proguanil was better tolerated than was mefloquine, and it was similarly effective for malaria prophylaxis in n onimmune travelers.