Chlorproguanil

Class:

Chlorproguanil is a biguanide.

Antiparasitic Activity:

Chlorproguanil combined with dapsone has recently been licensed for the treatment of falciparum malaria. This combination is more potent than pyrimethamine-sulfadoxine.

Mechanism of Action:

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.

Pharmacokinetics:

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.

Dosage:

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.

Adverse Effects:

Chlorproguanil has a high therapeutic index and reports of severe adverse effects are rare.

Drug Interactions:

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.