Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin to treat the parasite diseases toxoplasmosis and cystoisosporiasis. It is also used with dapsone as a second-line option to prevent Pneumocystis jiroveci pneumonia in people with HIV/AIDS. It was previously used for malaria but is no longer recommended due to resistance. Pyrimethamine is taken by mouth.
Common side effects include gastrointestinal upset, severe allergic reactions, and bone marrow suppression. It should not be used by people with folate deficiency that has resulted in anemia. There is concern that it may increase the risk of cancer. While occasionally used in pregnancy it is unclear if pyrimethamine is safe for the baby. Pyrimethamine is classified as a folic acid antagonist. It works by inhibiting folic acid metabolism and therefore the making of DNA.
Pyrimethamine is typically given with a sulfonamide and folinic acid.
It is used for the treatment of toxoplasmosis, actinomycosis, and isosporiasis, and for the treatment and prevention of Pneumocystis jirovecii pneumonia.
Pyrimethamine is also used in combination with sulfadiazine to treat active toxoplasmosis. The two drugs bind the same enzymatic targets as the drugs trimethoprim and sulfamethoxazole – dihydrofolate reductase and dihydropteroate synthase, respectively.
Pyrimethamine has also been used in several trials to treat retinochoroiditis.
Pyrimethamine is labeled as pregnancy category C in the United States. To date, not enough evidence on its risks in pregnancy or its effects on the fetus is available.
It is primarily active against Plasmodium falciparum, but also against Plasmodium vivax. Due to the emergence of pyrimethamine-resistant strains of P. falciparum, pyrimethamine alone is seldom used now. In combination with a long-acting sulfonamide such as sulfadiazine, it was widely used, such as in Fansidar, though resistance to this combination is increasing
When higher doses are used, as in the treatment of toxoplasmosis, pyrimethamine can cause gastrointestinal symptoms such as nausea, vomiting, glossitis, anorexia, and diarrhea. A rash, which can be indicative of a hypersensitivity reaction, is also seen, particularly in combination with sulfonamides. Central nervous system effects include ataxia, tremors, and seizures. Hematologic side effects such as thrombocytopenia, leukopenia, and anemia can also occur.
Other antifolate agents such as methotrexate and trimethoprim may potentiate the antifolate actions of pyrimethamine, leading to potential folate deficiency, anemia, and other blood dyscrasias.