pyrimethamine + leucovorin

**Pyrimethamine + leucovorin** is a combination therapy where pyrimethamine, a folic acid antagonist, inhibits dihydrofolate reductase (DHFR) in parasites like *Toxoplasma gondii* and *Cystoisospora belli*, blocking nucleic acid synthesis essential for parasite replication. Leucovorin (folinic acid) is co-administered to bypass pyrimethamine's inhibition of human DHFR, preventing bone marrow suppression and hematologic toxicity while providing no direct anti-parasitic activity. Primarily indicated for toxoplasmosis treatment and prophylaxis (including CNS, ocular, and congenital forms), cystoisosporiasis, and secondary prevention of *Pneumocystis jirovecii* pneumonia in immunocompromised patients, often combined with sulfonamides like sulfadiazine or alternatives such as clindamycin or atovaquone.[1][3][5]