Atovaquone and proguanil hydrochloride for prophylaxis of malaria

Background:The spread of drug-resistant malaria and appreciation of side ef fects associated with existing antimalarial drugs emphasize the need for ne w drugs to prevent malaria. The combination of atovaquone and proguanil hyd rochloride was previously shown to be safe and highly effective for treatme nt of malaria, including multi-drug-resistant Plasmodium falciparum. Methods:We reviewed results of clinical trials that evaluated either a fixe d-dose combination of atovaquone and proguanil hydrochloride for malaria pr ophylaxis or atovaquone alone for causal prophylactic activity against Fl f alciparum. Results: In three placebo-controlled trials, 331 subjects received 250 mg a tovaquone and 100 mg proguanil hydrochloride (or an equivalent dose based o n body weight in children) once daily for 10 to 12 weeks. The overall effic acy for preventing parasitemia was 98%. Among 175 nonimmune volunteers taki ng the same dose of atovaquone/proguanil once daily for 10 weeks while temp orarily residing in a malaria-endemic area, malaria developed in one patien t who was noncompliant with therapy. Results of volunteer challenge studies indicate that both atovaquone and proguanil have causal prophylactic activ ity directed against the liver stages of P. falciparum. Adverse events occu rred with similar or lower frequencies in subjects treated with atovaquone/ proguanil compared to placebo. Less than 1% of patients discontinued from t hese studies due to a treatment-related adverse event. Conclusion: A fixed-dose combination of atovaquone and proguanil hydroclori de is a promising new alternative for malaria prophylaxis.