Pharm

Pyrimethamine

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Pyrimethamine, Daraprim

  • See Also
  1. Pyrimethamine Sulfadoxine
  • Indications
  1. Toxoplasmosis in immunocompetent patients (FDA approved)
    1. Has been used off label for Toxoplasmosis in HIV and Congenital Toxoplasmosis
  2. Previously used to treat Malaria
    1. Replaced by other agents due to Malaria resistance to Pyrimethamine
    2. Has also been used as an antimalarial in combination with Sulfadoxine (Fansidar)
  • Contraindications
  1. G6PD Deficiency
    1. Risk of Hemolytic Anemia
  • Mechanism
  1. Synthetic derivative of ethyl Pyrimidine with antiparasitic and antimalarial activity
  2. Competitive inhibitor of dihydrofolate reductase (DHFR).
    1. DHFR is a key enzyme in Tetrahydrofolate synthesis, and in turn DNA and Protein synthesis
  • Medications
  1. Tablet: 25 mg
    1. Only available directly from manufacturer
  1. Used in combination with leucovorin and Sulfadiazine
    1. Combined with leucovorin to prevent hematologic adverse effects
    2. Combined with Sulfadiazine to broaden coverage
  2. Dosing is for immunocompetent patients
    1. See other resources for HIV related ToxoplasmosisEncephalitis
    2. See other resources for Congenital Toxoplasmosis
  3. Adult
    1. Start 50 to 75 mg orally daily for 1 to 3 weeks (use lower dose in Seizure Disorder)
    2. Next decrease dose 50% daily for an additional 5 weeks
  4. Child
    1. Start 1 mg/kg/day orally twice daily for 2 to 4 days
    2. Next decrease dose 50% for an additional 4 weeks
  • Adverse Effects
  1. Hypersensitivity Reaction
    1. Most commonly presents as a Cutaneous Drug Eruption (esp. when combined with a Sulfonamide)
  2. Hematologic Effects
    1. Thrombocytopenia, Leukopenia, and Anemia may occur
    2. Hemolytic Anemia with G6PD
  3. Gastrointestinal
    1. Nausea
    2. Vomiting
    3. Diarrhea
  4. Folate Deficiency
    1. Dose dependent
  5. Neurologic
    1. Seizures
    2. Ataxia
    3. Tremor
  • Safety
  1. Pregnancy Category C
  2. Considered safe in Lactation
  • Resources
  1. Pyrimethamine Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5368616d-6520-6f6e-2053-686b72656c69