Pyrimethamine

Indications
Oral
Acute malaria
Adult: As a single dose, in combination with a sulfonamide: 75 mg pyrimethamine with 1.5 g sulfadoxine.
Child: 7-13 yr: 50 mg pyrimethamine with 1 g sulfadoxine; 1-6 yr: 25 mg pyrimethamine with 500 mg sulfadoxine; 5-11 mth: 12.5 mg pyrimethamine and 250 mg sulfadoxine. To be taken as a single dose, in combination with a sulfonamide.
Oral
Prophylaxis of malaria
Adult: Pyrimethamine 25 mg as single dose once wkly. 1st dose should be taken 1-2 days before arrival in the endemic area, continue admin during stay and for 4-6 wk after leaving the area.
Child: <4 yr: 6.25 mg once wkly; 4-10 yr: 12.5 mg once wkly; >10 yr: 25 mg once wkly. 1st dose should be taken 1-2 days before arrival in the endemic area, continue admin during stay and for 4-6 wk after leaving the area.
Oral
Toxoplasmosis
Adult: 50-75 mg pyrimethamine daily with 1-4 g sulfadiazine daily. Continue at this dosage for 1-3 wk, depending on the patient's response and tolerance, then half the dosage and continue for another 4-5 wk.
Child: 1 mg/kg daily 2-4 days then 0.5 mg/kg daily for another 4 wk with usual paediatric dose of sulfadiazine.
Contraindications
Hypersensitivity, resistant malaria, megaloblastic anaemia secondary to folate deficiency. Pregnancy and lactation.
Warnings / Precautions
Renal or hepatic impairment; folate deficiency; monitor blood and platelet counts every 2 wk with prolonged treatment and large doses. Discontinue use if skin reactions, sore throats or shortness of breath occurs.
Adverse Reactions
Rashes, macrocytic anaemia (high dose), leucopenia, thrombocytopenia, megaloblastic anaemia, pancytopenia, abdominal pain, vomiting, atrophic glossitis.
Potentially Fatal: Cutaneous reactions e.g. erythema multiforme and Stevens-Johnson syndrome and toxic epidermal necrolysis with sulfadoxine at large doses.
Drug Interactions
Lorazepam may induce hepatotoxicity. Increased risk of bone marrow suppression when used with agents that have myelosuppressive properties e.g. proguanil, sulfonamides, zidovudine and cytostatic agents. Increased risk of serious pancytopenia and megaloblastic anaemia when used with co-trimoxazole or other sulfonamides.
See Below for More pyrimethamine Drug Interactions
Mechanism of Actions
Pyrimethamine is a folic acid antagonist structurally similar to trimethoprim. It inhibits parasitic dihydrofolate reductase, thus inhibiting vital tetrahydrofolic acid synthesis. It is active against pre-erythrocytic forms and is also a slow-acting schizontocide.
Onset: Approx 1 hr.
Absorption: Almost completely absorbed.
Distribution: 80-90% bound to plasma proteins. Crosses the placenta and passes into the breast milk.
Metabolism: Metabolised in the liver.
Excretion: Excreted via kidney. Half-life is about 4 days.
Administration
Should be taken with food.
ATC Classification
P01BD01 - pyrimethamine ; Belongs to the class of diaminopyrimidine antimalarials.
Available As
  • Pyrimethamine 12.5 mg
  • Pyrimethamine 18.75 mg
  • Pyrimethamine 20 mg
  • Pyrimethamine 25 mg
  • Pyrimethamine 37.5 mg
  • Pyrimethamine 50 mg
  • Pyrimethamine 75 mg
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