PYRIMETHAMINE

Folate antagonist antimicrobial agent

Dosage Forms

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Tablet

25 mg

Uses

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  • Toxoplasmosis (with sulfadiazine)
  • Malaria (with sulfadoxine)

Dose and Duration

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Prevention of congenital transmission of toxoplasmosis (in 2ⁿᵈ and 3ʳᵈ trimesters of pregnancy)

Adult: by mouth, 25 mg daily for 3–4 weeks

Treatment of toxoplasmosis in neonates

Neonate: by mouth, 1 mg/kg daily. Continue treatment for 6 months in overt disease or treat for 4 weeks if born to mother infected during pregnancy, followed by further courses if infection is confirmed

Treatment of toxoplasmosis in immunodeficiency

Adult: by mouth, 200 mg in divided doses on day 1, followed by 75–100 mg daily for at least 6 weeks. Continue treatment with a suppressive dose of 25–50 mg daily

Chorioretinitis

Adult: by mouth, 75 mg daily for 3 days, then 25 mg daily for 4 weeks. If patient is unresponsive, give 50 mg daily for a further 4 weeks

Treatment of malaria (with sulfadoxine)

Sulfadoxine 500 mg and pyrimethamine 25 mg

3 tablets taken at once, 2 times during pregnancy

→ First dose: Between weeks 16–24

→ Second dose: Between weeks 28–36

Contra-indications

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  • History of pyrimethamine sensitivity

Side Effects

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  • Leucopoenia, thrombocytopenia, megaloblastic anaemia
  • Headache, dizziness
  • Vomiting, nausea, diarrhoea
  • Rash

Interactions

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  • Artemether + lumefantrine (avoid concomitant use)
  • Citalopram (risk of ventricular arrhythmias)
  • Methotrexate (antifolate effect of methotrexate increased)
  • Phenytoin (antagonism of anticonvulsant effect; increased antifolate effect)
  • Silver sulfadiazine, sulfadiazine, sulfamethoxazole + trimethoprim, trimethoprim (increased antifolate effect)

Pregnancy

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  • Do not use in 1ˢᵗ trimester

Breast-feeding

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  • Can be used

⚠️ Caution

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  • Use with caution in hepatic and renal impairment
  • Pyrimethamine is present in significant amounts in breast milk. Avoid administration of other folate antagonists to infant. Avoid breast-feeding in toxoplasmosis treatment
  • In prolonged treatment, give folate throughout and carry out blood counts weekly (twice weekly in immunocompromised) and for a further 2 weeks after stopping treatment. Discontinue treatment if signs of folate deficiency develop and give high dose calcium folinate
  • Avoid large loading doses in patients with a history of seizures