Proguanil is a biguanide.
Proguanil alone is used only for the prevention of falciparum malaria, although cycloguanil also has in vitro activity against T. gondii.
Proguanil acts by inhibition of dihydrofolate reductase after cytochrome P450-catalysed cyclization.
Resistance occurs through multiple mutations in the gene coding for this enzyme.
Proguanil is well absorbed after oral dosage. The t1/2 is about 16.5 hours; about 60% of a dose of proguanil is excreted unchanged in the urine. Proguanil is essentially a pro-drug as it is metabolized to cycloguanil and 4-chlorophenyl-biguanide, the former being a potent antimalarial compound.
Daily proguanil (200 mg adult dose, which may be divided or taken in one dose) is most often taken with weekly chloroquine for the prevention of falciparum malaria.
In patients with renal dysfunction, proguanil is relatively contraindicated.
Proguanil has a high therapeutic index and reports of severe adverse effects are rare. Temporary hair loss and mouth ulcers may occur with prolonged dosage
No significant clinical drug interactions involving proguanil have been reported
Proguanil has not been shown to cause birth defects or other problems in humans. However, it is recommended that pregnant women can avoid travelling to areas where there is a chance of contacting malaria.
Proguanil is available as Proguanil Tablets BP or BNF [tablets containing Proguanil hydrochloride, and as PaludrineŽ manufactured by AstraZeneca [tablets containing Proguanil hydrochloride].