atovaquoneproguanil

Atovaquone/proguanil is a fixed-dose combination antimalarial medication containing atovaquone and proguanil hydrochloride, marketed under the brand name Malarone. It is used for the treatment of uncomplicated Plasmodium falciparum malaria and for malaria prophylaxis in travelers to endemic areas.

The two components act synergistically: atovaquone inhibits the parasite’s mitochondrial electron transport chain, collapsing the mitochondrial membrane potential, while proguanil is a prodrug of cycloguanil that inhibits dihydrofolate reductase, impairing DNA synthesis. Together, they rapidly kill the parasite and help prevent resistance when used as prescribed.

Administration and dosing: For treatment of acute malaria, the typical adult and pediatric regimen is four tablets taken once daily for three days. For prophylaxis, one tablet once daily, starting 1–2 days before travel and continuing during the stay, with the final dose 7 days after leaving the area. The drug should be taken with food or a fatty meal to enhance absorption.

Safety and contraindications: It should not be used in individuals with known hypersensitivity to atovaquone or proguanil. Pregnancy should be avoided unless clearly needed; caution is advised in hepatic impairment and in renal impairment, where dose adjustments may be necessary. Common adverse effects include nausea, vomiting, abdominal pain, headache, and rash; rare but serious effects can include liver toxicity and severe skin reactions.

Interactions and resistance: Concomitant use with rifampin markedly reduces atovaquone levels and may reduce efficacy; cholestyramine can decrease absorption. Resistance may involve mutations in the parasite’s cytochrome bc1 complex or in dihydrofolate reductase.

History and regulatory status: As a fixed-dose combination, atovaquone/proguanil has been approved for treatment and prophylaxis of malaria in many countries, including the United States and the European Union.