Atovaquone-proguanil for prophylaxis and treatment of malaria.
OBJECTIVE
To review the currently available information on atovaquone-proguanil for treatment and prophylaxis of malaria.


METHODS
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.


METHODS
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.


RESULTS
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.
Marra
Fawziah
F
Faculty of Pharmaceutical Sciences, University of British Columbia, and Pharmacy and Vaccine Services, British Columbia Centre for Disease Control, Vancouver, Canada. fawziah.marra@bccdc.ca
Salzman
James R
JR
Ensom
Mary H H
MH
D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053626:Atovaquone; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000517:prevention & control*; D009285:Naphthoquinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002727:Proguanil / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000962:Antimalarials; D009285:Naphthoquinones; D002727:Proguanil; D053626:Atovaquone