[4] Side effects include diarrhea, constipation, skin rashes, hair loss, and itchiness.

[6] When the Japanese attack on Pearl Harbor started World War II in the Pacific, the US became very interested in antimalarial medications and funded a large joint US-UK program to find new non-toxic and easy to produce drugs of the type.

[7] It was joined by a team led by Frank Rose at the Medical Chemicals Section of Imperial Chemical Industries (later Pharmaceuticals Division, which ended up demerged into Zeneca) at Blackley, which earlier developed a way to manufacture mepacrine, an antimalarial made exclusively in Germany before the war.

[7] Rose and his colleague Frank Curd decided to concentrate on pyrimidines as relatively simple to synthetise, even though the Advisory Panel recommended against that because most antimalarials by then were either quinolines or acridines.

Checking prospective 2,4-diaminopyridine derivatives with a basic side chain and a benzenoid moiety one after another, they noticed a geometric pattern in the effective analogs and wondered if they could reproduce their interesting biologic activity with molecules even simpler, without the pyrimidine ring, and tried biguanides (then called diguanides) with which Rose was familiar due to his earlier sulphonamide research to great effect.

[12] There have also been reports of increased levels of liver enzymes, which may remain high for up to 4 weeks after completion of treatment.

"[17] Proguanil lowers the effective concentration of atovaquone needed to increase permeability of the mitochondrial membrane.