Malaria treatment Atovaquone/proguanil is not normally used to treat severe malaria, when an injectable drug such as
quinine is used instead.
Malaria prevention Since some malaria strains are resistant to atovaquone/proguanil, it is not effective in all parts of the world. It must be taken with a fatty meal, or at least some milk, for the body to absorb it adequately—and to avoid painful stomach irritation, which proguanil frequently causes if taken without food.
Resistance Proguanil acts as a
mitochondrial sensitiser and synergizes with atovaquone. When atovaquone is used as a sole agent, a high natural frequency of
cytochrome b mutants leads to a high failure rate. This is potentially due to the high lipophilicity and slow uptake of atovaquone, which results in a relatively prolonged period of parasite exposure at ineffective concentrations. Specific mutations (
Y268S,
Y268C) have been shown to confer resistance
in vivo, but the other mechanisms of resistance remain unknown. ==Adverse effects==