Chlorproguanil (PDF Version)
Chlorproguanil is a biguanide.
Chlorproguanil combined with dapsone has recently been licensed for the treatment of falciparum malaria. This combination is more potent than pyrimethamine-sulfadoxine.
Chlorproguanil acts by inhibition of dihydrofolate reductase after cytochrome P450-catalysed cyclization.
Mechanism of Resistance:
Resistance occurs through multiple mutations in the gene coding for this enzyme.
Chlorproguanil is rapidly and extensively absorbed. The t1/2 of chlorproguanil is about 12 hours, but individual values vary widely. Like proguanil, chlorproguanil is essentially a pro-drug with the active metabolite chlorcycloguanil detectable in the plasma within the first 6 hours of oral dosing.
Lapdap™ comprises 2.0 and 2.5 mg/kg respectively of chlorproguanil and dapsone. It is given daily for three days for the treatment of uncomplicated falciparum malaria.
Chlorproguanil has a high therapeutic index and reports of severe adverse effects are rare.
No clinically-significant interactions have been reported.
Pregnancy:
There is no information available but this is an off-label use at present.
Brand names/Manufacturer:
Lapdap™; Glaxo SmithKline (chlorproguanil 80 mg + dapsone 100 mg per caplet, for adults, and chlorproguanil 15 mg +dapsone 18.75 mg per caplet for children).
Lapudrine™ (chlorproguanil) (Zeneca) is no longer available.