atovaquone

Atovaquone is an antiparasitic and antiprotozoal medication used to treat and prevent certain infections. It is marketed alone for Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment in patients who cannot tolerate trimethoprim-sulfamethoxazole, and it is also used in combination with azithromycin to treat babesiosis. In addition, the combination drug atovaquone-proguanil (brand name Malarone) is used for malaria prophylaxis and treatment, particularly for Plasmodium falciparum.

Mechanism of action: Atovaquone inhibits mitochondrial electron transport in susceptible parasites by blocking the cytochrome bc1 complex, causing collapse of the mitochondrial membrane potential and inhibition of nucleotide and nucleic acid synthesis. Because parasite mitochondria differ from human mitochondria, the drug is selectively active against the pathogen.

Pharmacokinetics and administration: Oral bioavailability is increased with fatty meals. Atovaquone is highly protein-bound and distributes widely in body tissues. It is primarily excreted in the feces and has a half-life of several days. Dosing and duration depend on the indication and regimen.

Adverse effects and safety: Common adverse effects include gastrointestinal upset, headache, and rash. Hepatic enzyme elevations have been reported, and rare cases of severe hepatotoxicity or hypersensitivity occur. Use during pregnancy and lactation should be guided by a risk-benefit assessment, and alternative options may be considered when appropriate.

Interactions and notes: Concurrent use with rifampin can reduce atovaquone levels, and cholestyramine can decrease absorption. Absorption is enhanced when taken with a fatty meal. Liver function may require monitoring during prolonged use, and patients should be advised on potential drug interactions.