Proguanil

Proguanil (chlorguanide, chloroguanide) is a prophylactic antimalarial drug. When taken, it is converted to the active metabolite cycloguanil. Proguanil is effective against sporozoites. Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.

It has been used for malarial prophylaxis in children with sickle cell disease living in malaria-endemic areas for many years.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.

Medical uses
Proguanil is usually taken in combination with another antimalarial drug, such as atovaquone (e.g. in the combination Malarone) or chloroquine.

Malarone has fewer side effects than mefloquine, but can be more expensive because it is taken daily.

Proguanil is taken with atovaquone for chloroquine-resistant and multidrug resistant strains of P. falciparum and P. vivax. Proguanil combined with atovaquone is sold under the tradename Malarone (GlaxoSmithKline).

Precautions
General precautions regarding proguanil involve watching out for feelings of sullenness and anxiety to a level outside the ordinary, when taking it over a period of several months. These may come on gradually and may not be immediately attributable to anything in particular.

Mechanism
It works by stopping the malaria parasites, Plasmodium falciparum and Plasmodium vivax, from reproducing once they are inside red blood cells, by inhibiting the enzyme dihydrofolate reductase, which catalyzes the formation of tetrahydrofolate, the main one-carbon unit carrier in the body, required for dTMP and purine base synthesis.