atovaquónproguanil

Atovaquone‑proguanil is a fixed‑dose combination antimalarial medication used for the treatment, prevention and prophylaxis of malaria caused by Plasmodium species. The drug pairs atovaquone, a hydroxyl‑phenyl-2‑quinolone that inhibits the parasite’s mitochondrial electron transport chain, with proguanil, a 2‑chloroguanidine that interferes with the parasite’s dihydrofolate reductase leading to impaired nucleic acid synthesis. In combination, the two agents provide synergistic activity and reduce the risk of resistance emerging, particularly in Plasmodium falciparum.

The manufacturer sells the product under the brand name Malarone, though it is also available as generic preparations. It is taken orally, usually twice daily for 3 days to treat acute malaria after a loading dose of 1 g at selected times. For prophylaxis of travelers to endemic regions, the recommended regimen is one tablet daily, starting 1‑2 weeks before travel, throughout the stay and for 4 weeks after leaving the endemic area. Dosage adjustments are made for pregnancy, lactation or severe renal or hepatic dysfunction; the drug is contraindicated in severe hepatic impairment.

Common adverse effects include headache, nausea, fatigue, dizziness and mild gastrointestinal upset. Less common but serious reactions are hypersensitivity, severe skin lesions (Stevens‑Johnson syndrome), and reversible liver enzyme elevations. Drug interactions occur primarily through the inhibition of cytochrome P450 enzymes; concomitant use with hepatotoxic agents or drugs requiring hepatic metabolism (e.g., warfarin, tamoxifen) warrants caution.

Regulatory approvals encompass the World Health Organization’s pre‑qualified list and approvals by the US Food and Drug Administration and European Medicines Agency for therapeutic use in populations at risk of malaria infection worldwide.