Atovaquone-proguanil

Atovaquone-proguanil, made by Smith Kline Glaxo and approved by the U.S. Food and Drug Administration in 2000, is a fixed-combination antimalarial drug for chemoprophylaxis and treatment.

Mechanism of action
The two components block with two different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil hydrochloride primarily exerts its effect by means of the metabolite cycloguanil, a dihydrofolate reductase inhibitor. Inhibition of dihydrofolate reductase in the malaria parasite disrupts deoxythymidylate synthesis.

Drug-drug interactions
There are adverse interactions with tetracycline, metoclopramide and rifampin.