Atovaquone with Proguanil Hydrochloride

How it works

Atovaquone inhibits the parasite mitochondrial cytochrome bc1 complex while proguanil, via its metabolite cycloguanil, inhibits dihydrofolate reductase; together they act synergistically and proguanil also potentiates the membrane effect of atovaquone.

Prescribing in practice

• Take with food or a milky drink to ensure adequate atovaquone absorption, and repeat the dose if vomiting occurs shortly after, as poor absorption can lead to prophylaxis failure.
• It is not recommended for malaria prophylaxis in severe renal impairment because of reduced proguanil clearance, where an alternative agent should be chosen.
• For prophylaxis it should be started before travel and continued for the recommended period after leaving the malarial area.

Monitoring

Monitoring is mainly clinical, ensuring adherence and absorption, with renal function considered before prophylactic use in at-risk patients.

Counselling the patient

• Take each dose with food or a milky drink at the same time each day.
• Continue the course after returning home for as long as instructed to remain protected.
• Use mosquito-bite precautions as well, since no antimalarial is fully protective, and seek urgent care for any fever after travel.

Evidence & guidelines

Atovaquone with proguanil is a recommended option for malaria prophylaxis and uncomplicated falciparum malaria treatment in UK malaria prevention guidelines.