Atovaquone/Proguanil

Atovaquone/proguanil is the generic version of Malarone, used for the prevention and treatment of falciparum malaria. This combination is the most commonly recommended antimalarial for travellers to areas of chloroquine-resistant malaria because of its convenient dosing schedule and favourable side-effect profile.

How does the combination work?

Atovaquone inhibits mitochondrial electron transport in the malaria parasite, disrupting its energy metabolism. Proguanil is metabolised to cycloguanil, which inhibits dihydrofolate reductase, blocking parasite DNA synthesis. In addition, proguanil enhances the mitochondrial membrane-collapsing activity of atovaquone, even independently of its metabolite. The dual action provides synergistic antimalarial activity and reduces the chance of resistance developing.

Why is the post-travel course so short?

Unlike doxycycline and mefloquine, which only act on blood-stage parasites, atovaquone/proguanil has causal prophylactic activity against the liver stage of Plasmodium falciparum. By killing parasites in the liver before they reach the bloodstream, it allows the post-exposure course to be shortened to just seven days instead of four weeks.

How to Take Atovaquone/Proguanil

Take one tablet once daily with food or a milky drink at the same time each day. Start 1 to 2 days before entering the malaria area, continue every day throughout your stay, and carry on for 7 days after returning home.

Taking atovaquone/proguanil with a fatty meal substantially increases absorption. A glass of full-fat milk is sufficient if a full meal is not practical. If you vomit within an hour of taking the tablet, take another dose as soon as possible.

Prevention: one adult tablet (250 mg atovaquone / 100 mg proguanil) daily. Start one to two days before travel, take daily during the stay, and continue for seven days after return. Treatment of acute malaria: four adult tablets as a single daily dose for three consecutive days.

Common side effects

• Headache
• Abdominal pain
• Nausea and vomiting
• Diarrhoea
• Cough

Tolerability

Atovaquone/proguanil is generally better tolerated than mefloquine (fewer neuropsychiatric effects) and doxycycline (no photosensitivity or vaginal thrush). GI symptoms are usually mild and manageable.

If vomiting occurs within one hour of taking the dose, take a replacement dose. The combination is not recommended for severe or complicated malaria, which requires parenteral treatment. No antimalarial provides 100% protection; travellers should also use insect repellent, mosquito nets, and protective clothing.

Renal impairment

Not recommended for prophylaxis in severe renal impairment (creatinine clearance below 30 ml/min).

Contraindicated in severe renal impairment for prophylactic use, and in known hypersensitivity to atovaquone or proguanil.