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Guidelines for the treatment of malaria – 2 edition

• Tablets containing 500 mg of sulfadoxine and 25 mg of pyrimethamine.
• Ampoules containing 500 mg of sulfadoxine and 25 mg of pyrimethamine in 2.5 ml
of injectable solution for intramuscular use.

Pharmacokinetics

Pyrimethamine is almost completely absorbed from the gastrointestinal tract and peak
plasma concentrations occur 2–6 h after an oral dose. It is mainly concentrated in the
kidneys, lungs, liver and spleen, and about 80–90% is bound to plasma proteins. It is
metabolized in the liver and slowly excreted via the kidneys. The plasma half-life is
around 4 days. Pyrimethamine crosses the blood-brain barrier and the placenta and is
detectable in breast milk. Absorption of the intramuscular preparation is incomplete and
insufficiently reliable for this formulation to be recommended (14).

Toxicity
Pyrimethamine is generally very well tolerated. Administration for prolonged periods may
cause depression of haematopoiesis due to interference with folic acid metabolism. Skin
rashes and hypersensitivity reactions also occur. Larger doses may cause gastrointestinal
symptoms such as atrophic glossitis, abdominal pain and vomiting, haematological effects
including megaloblastic anaemia, leukopenia, thrombocytopenia and pancytopenia, and
central nervous system effects such as headache and dizziness.

Acute overdosage of pyrimethamine can cause gastrointestinal effects and stimulation
of the central nervous system with vomiting, excitability and convulsions. Tachycardia,
respiratory depression, circulatory collapse and death may follow. Treatment of overdosage
is supportive.

Drug interactions
Administration of pyrimethamine with other folate antagonists such as cotrimoxazole,
trimethoprim, methotrexate or phenytoin may exacerbate bone marrow depression. Given
with some benzodiazepines, there is a risk of hepatotoxicity.