Section 15 · Monograph
Pyrimethamine
Reviewed Nov 2026FDA label
DaraprimAntiparasitic (DHFR inhibitor)
- Forms
- Tab: 25mg
- Dose
- Cerebral toxoplasmosis: 200mg load, then 50mg (under 60kg) or 75mg (60kg or more) daily with sulfadiazine and leucovorin
- MOA
- Inhibits Toxoplasma dihydrofolate reductase
Indications
- Treatment of toxoplasmosis (with a sulfonamide)FDA-labeled
Off-Label Uses
- Prophylaxis of toxoplasmic encephalitis in HIVOff-label
Mechanism of Action
- Inhibits Toxoplasma dihydrofolate reductase, blocking folate synthesis; leucovorin protects human marrow without rescuing the parasite
Full Dosing
Adult / usual
- Acute cerebral toxoplasmosis: 200mg once as loading dose, then 50mg daily (under 60kg) or 75mg daily (60kg or more) with sulfadiazine and leucovorin (folinic acid) 10-25mg daily; extended to 50mg if needed
- Treat for at least 6 weeks, then secondary prophylaxis at lower doses until immune recovery
Contraindications
- Known hypersensitivity to pyrimethamine
- Megaloblastic anemia due to folate deficiency (relative)
Drug Interactions
- Other antifolates (TMP-SMX, methotrexate): additive myelosuppression
- Lorazepam: possible hepatotoxicity reports
Adverse Effects
- Bone marrow suppression (megaloblastic anemia, leukopenia, thrombocytopenia)
- Rash, nausea
- Seizures at overdose
Monitoring Parameters
- CBC with differential at least twice weekly during acute therapy
- Folate status and leucovorin adherence
- Rash
Pregnancy & Lactation
- Teratogenic in animals; use during pregnancy only when benefit outweighs risk, with folinic acid
- Excreted in milk