What is the treatment for pyrimethamine (antimalarial medication) poisoning?

Treatment of Pyrimethamine Poisoning

The primary treatment for pyrimethamine poisoning is immediate administration of leucovorin (folinic acid) to counteract the bone marrow suppression caused by pyrimethamine toxicity. 1

Pathophysiology and Toxicity

Pyrimethamine is an antimalarial and anti-toxoplasmosis medication that works by inhibiting dihydrofolate reductase, which is essential for folate metabolism. Poisoning primarily affects:

• Bone marrow, causing neutropenia, anemia, and thrombocytopenia 1
• May cause rash (including Stevens-Johnson syndrome) and gastrointestinal symptoms 1
• Can be fatal in high doses, as demonstrated in a 2012 incident where cardiac patients accidentally received 100mg daily (normal therapeutic dose for malaria is 25mg/week) 2

Treatment Protocol

Immediate Interventions

1. Administer leucovorin (folinic acid) at increased doses based on severity of poisoning 1

   • Start with 10-25 mg/day and increase as needed based on hematologic parameters 1
   • Continue leucovorin for at least 1 week after pyrimethamine has been discontinued due to the drug's long half-life 1

2. Supportive care:

   • Monitor complete blood count at least weekly 1
   • Provide fluid support and address electrolyte imbalances 1
   • Treat symptomatic manifestations (antiemetics for nausea/vomiting) 1

Monitoring

• Perform complete blood count monitoring at least weekly to assess bone marrow recovery 1
• Monitor renal and hepatic function 1
• Watch for cutaneous reactions which may require additional interventions 1

Special Considerations

Pediatric Patients

• Adjust leucovorin dosing based on weight and severity of poisoning 1
• Children may be more susceptible to bone marrow suppression effects 1

Pregnant Women

• Leucovorin is safe during pregnancy and should be administered immediately 1, 3
• Pyrimethamine is teratogenic when used in the first trimester, but treatment of poisoning with leucovorin takes priority 3, 4

Common Pitfalls

• Failure to continue leucovorin long enough: Due to pyrimethamine's long half-life, leucovorin must be continued for at least 1 week after the last dose of pyrimethamine 1
• Inadequate monitoring: Complete blood counts should be performed frequently to assess bone marrow recovery 1
• Concurrent administration of other folate antagonists: Avoid trimethoprim-sulfamethoxazole during treatment as it may worsen adverse effects 3

Treatment Algorithm

1. Confirm pyrimethamine poisoning based on history and symptoms
2. Initiate leucovorin immediately at appropriate doses
3. Monitor complete blood count and adjust leucovorin dose as needed
4. Continue leucovorin for at least 1 week after last pyrimethamine exposure
5. Provide supportive care for symptomatic manifestations
6. Monitor for recovery of bone marrow function before discontinuing treatment