Pyrimethamine

Pyrimethamine is an antimalarial drug that is used in combination with sulfonamides (sulfadiazine or triple sulfonamide). The drug has also been used in combination with the long-acting sulfaderivates sulfadoxine (Fansidar) or sulfametopyrazine (Dapsone) which can be given as a weekly once dosage. Pyrimethamine has been accepted as the drug of choice for treatment of toxoplasmosis since the beginning of the 1950s (WHO 1990). Hitherto, no other drug, alone or in combination, has been shown to be superior to the pyrimethamine-sulfa combination. Both drugs are folic acid antagonists, which act synergistically to suppress the proliferation of tachyzoites by impairment of DNA synthesis. Their

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combined activity is 10 times greater than expected if their effects were merely additive (Sheffield and Melton 1975; Derouin and Chastang 1989).

Pyrimethamine is capable of penetrating the blood brain and the blood retina barriers and concentrates in both the brain and the retinal tissue (Remington et al. 1995).

The half-life of pyrimethamine is 4-5 days. The oral dose is usually 0.5-1mg/kg per day. The tablet may be crushed and administered in a suspension with juice or food. The most common side effects are those related to suppression of the bone marrow. Peripheral white blood cells and platelet count should be regularly monitored during treatment. Adding folinic acid (not folic acid) 3-10mg every third day may prevent the haematological complication. Other less-serious side effects include nausea, headache, and an unpleasant taste in the mouth.

In humans pyrimethamine has no proven teratogenic effect. In 1978 WHO approved the free use of Fansidar (pyrimethamine 25 mg + sulfadoxine 500 mg) as malaria prophylaxis during pregnancy, while an editorial in Lancet (1983) stated that pyrimethamine was safe even during early pregnancy - if folinic acid is added as a supplement. However, as a precaution in the first trimester pyrimethamine is usually replaced by spiramycin (WHO 1988).

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