Pyrimethamine with or without sulphonamides

• Pyrimethamine (Daraprim®) was previously used as a preventive agent, but leads to rapid resistance if it is the only product used. The mechanism of action is the same as that of proguanil. The product is also used in the treatment of toxoplasmosis. In long-term administration megaloblastic anaemia may occur (folic acid antagonism).

• Maloprim® or Deltaprim® The combination of pyrimethamine (12.5 mg) with dapsone (100 mg) was and still is used as prophylaxis in some regions, including Zimbabwe and South Africa. It is only slightly effective and the indications diminish from year to year. Dapsone is removed from the body quite rapidly (t½ = 28 hours). It cannot be used as a curative drug.

• Fansidar® is a combination product of pyrimethamine 25 mg and sulphadoxine 500 mg per tablet (Mekalfin® is another commercial name). Sulphadoxine is a long-acting sulphonamide (t½ = 8 days) which in case of allergy may cause severe skin lesions (erythema multiforme and Stevens-Johnson syndrome). For this reason it is best not used for prevention. Plasmodium falciparum has developed resistance to this product in some parts of the world. The curative dose for an adult of 70 kg is 3 tablets taken as one dose. The action is slow. The idea behind the combination of pyrimethamine with a sulphonamide is the sequential inhibition of tetrahydrofolic acid formation which is necessary for purine and pyrimidine (DNA precursors) synthesis. Theoretically there is a risk of icterus (and kernicterus) if pregnant women use it, but this risk is very limited.

Category: Medicine Notes