II. 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)

III. Contraindications

IV. 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

V. Medications

  1. Tablet: 25 mg
    1. Only available directly from manufacturer

VI. Dosing: Toxoplasmosis in Immunocompetent Patients

  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

VII. 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

VIII. Safety

  1. Pregnancy Category C
  2. Considered safe in Lactation

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Pyrimethamine (C0034283)

Definition (NCI) A synthetic derivative of ethyl-pyrimidine with potent antimalarial properties. Pyrimethamine is a competitive inhibitor of dihydrofolate reductase (DHFR). DHFR is a key enzyme in the redox cycle for production of tetrahydrofolate, a cofactor that is required for the synthesis of DNA and proteins. This agent is often used in combination with other antimalarials for the treatment of uncomplicated falciparum malaria. (NCI04)
Definition (MSH) One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.
Definition (PDQ) A synthetic derivative of ethyl-pyrimidine with potent antimalarial properties. Pyrimethamine is a competitive inhibitor of dihydrofolate reductase (DHFR). DHFR is a key enzyme in the redox cycle for production of tetrahydrofolate, a cofactor that is required for the synthesis of DNA and proteins. This agent is often used in combination with other antimalarials for the treatment of uncomplicated falciparum malaria. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39578&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39578&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C788" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D011739
SnomedCT 373769001, 59589008
LNC LP32679-0, MTHU016256
English Pyrimethamine, pyrimethamine, 2,4-Pyrimidinediamine, 5-(4-chlorophenyl)-6-ethyl-, pyrimethamine (medication), PYRIMETHAMINE, Pyrimethamine [Chemical/Ingredient], Pyrimethamine product, Pyrimethamine (product), Pyrimethamine (substance)
Swedish Pyrimetamin
Czech pyrimethamin
Finnish Pyrimetamiini
Russian PIRIMETAMIN, KHLORIDIN, ПИРИМЕТАМИН, ХЛОРИДИН
Japanese ピリメタミン
Polish Pirymetamina, Daraprim
Spanish pirimetamina (producto), pirimetamina (sustancia), pirimetamina, Pirimetamina
French Pyriméthamine
German Pyrimethamin
Italian Pirimetamina
Portuguese Pirimetamina

Ontology: Daraprim (C0591326)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D011739
English Daraprim, Glaxo Wellcome Brand of Pyrimethamine, GlaxoSmithKline Brand of Pyrimethamine, Wellcome Brand of Pyrimethamine