Atovaquone–Proguanil for Prophylaxis and Treatment of Malaria

Abstract

OBJECTIVE: To review the currently available information on atovaquone–proguanil for treatment and prophylaxis of malaria. DATA SOURCES: A MEDLINE search was conducted from 1966 to February 2003 using key phrases Malarone, atovaquone, proguanil, and malaria. Further articles were identified from a manual search of the references of identified articles. STUDY SELECTION AND DATA EXTRACTION: English-language studies with animal and human data evaluating preclinical pharmacology, human studies on pharmacokinetics, and clinical trials were evaluated. Relevant data were extracted from identified articles. DATA SYNTHESIS: Atovaquone–proguanil has been evaluated for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum in 8 clinical trials. In these studies, treatment with atovaquone–proguanil led to a higher (87–100% vs. 72–88%) or equally effective (94–100% vs. 90–100%) cure rate than the comparator antimalarial agents. Atovaquone–proguanil has been evaluated for prophylaxis of malaria in 6 clinical trials. In the 4 placebo-controlled trials for semi-immune residents or nonimmune migrants, the prophylaxis success rates in the atovaquone–proguanil and placebo arms ranged from 98% to 100% and 48% to 82%, respectively. The prophylaxis with success rates were similar among the 2 arms when atovaquone–proguanil was compared with other antimalarial regimens in nonimmune travelers. Atovaquone–proguanil was well tolerated in these clinical trials. CONCLUSIONS: Atovaquone–proguanil is a safe and effective alternative to current recommended regimens for prophylaxis and treatment of malaria.