Treatment of Pyrimethamine Poisoning

Pathophysiology and Toxicity

Pyrimethamine poisoning primarily affects the bone marrow, causing neutropenia, anemia, and thrombocytopenia, as well as potentially causing rash and gastrointestinal symptoms in a population taking the medication for antimalarial or anti-toxoplasmosis purposes 1, 3
The Centers for Disease Control and Prevention recommends considering the effects of pyrimethamine on bone marrow and other systems when treating patients with this medication 1

The primary treatment for pyrimethamine poisoning is immediate administration of leucovorin (folinic acid) to counteract the bone marrow suppression caused by pyrimethamine toxicity, with a recommended starting dose of 10-25 mg/day and adjustment based on hematologic parameters in patients with severe poisoning 1, 3
The American College of Medical Toxicology recommends supportive care, including monitoring of complete blood count at least weekly, fluid support, and treatment of symptomatic manifestations, such as nausea and vomiting, in patients with pyrimethamine poisoning 1, 3

In pediatric patients, leucovorin dosing should be adjusted based on weight and severity of poisoning, and children may be more susceptible to bone marrow suppression effects, according to the American Academy of Pediatrics 1, 3
The Centers for Disease Control and Prevention recommends that leucovorin is safe during pregnancy and should be administered immediately in pregnant women with pyrimethamine poisoning 3

Failure to continue leucovorin long enough, due to pyrimethamine's long half-life, can lead to inadequate treatment, and the American College of Medical Toxicology recommends continuing leucovorin for at least 1 week after the last dose of pyrimethamine 1
Inadequate monitoring, including infrequent complete blood counts, can lead to delayed detection of bone marrow recovery, and the Centers for Disease Control and Prevention recommends frequent monitoring 1