Adult: In combination with a sulfonamide or another appropriate antibacterial: Initially, 100 mg for 1-2 days then 25-50 mg daily. Alternatively, 50-75 mg daily in combination with a sulfonamide and leucovorin calcium, for 1-3 weeks depending on patient response and tolerability. Dose may be reduced by 50% and continued for 4-5 weeks. Child: In combination with a sulfonamide or another appropriate antibacterial: 5-6 years Initially, 2mg/kg (Max: 50 mg), then 1mg/kg (Max: 25 mg) daily; >6 years Same as adult dose.
Administration
Should be taken with food.
Contraindications
Hypersensitivity. Megaloblastic anaemia secondary to folate deficiency. 1st trimester of pregnancy. Lactation.
Special Precautions
Patient with seizure disorders, G6PD deficiency, folate deficiency (e.g. malabsorption syndrome, alcoholism). Renal and hepatic impairment. Children. Pregnancy (2nd and 3rd trimester).
Adverse Reactions
Significant: Megaloblastic anaemia, leucopenia, thrombocytopenia, pancytopenia; crystalluria (with sulfonamides). Cardiac disorders: Cardiac arrhythmia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, glossitis. General disorders and administration site conditions: Fever. Immune system disorders: Anaphylaxis. Metabolism and nutrition disorders: Anorexia. Nervous system disorders: Headache, dizziness. Skin and subcutaneous tissue disorders: Rash, abnormal skin pigmentation, dermatitis.
Monitor CBC and platelets twice weekly in high dose therapy; hepatic and renal function.
Overdosage
Symptoms: Severe and repeated vomiting, nausea, abdominal pain, convulsions, ataxia, tremor, and respiratory depression. Management: Symptomatic and supportive treatment. Maintain the airways and perform gastric lavage. May administer diazepam to control convulsions; calcium folinate for possible folinate deficiency.
Drug Interactions
May cause convulsion with methotrexate in patient with CNS leukaemia, and seizures with antimalarial drugs. Further depression of folate metabolism with co-trimoxazole, proguanil, zidovudine, or cytostatic agents (e.g. methotrexate). Decreased absorption with antacids and kaolin. Increased risk of hepatotoxicity with lorazepam. Potentially Fatal: May cause bone marrow aplasia with daunorubicin, cytosine arabinoside in patient with acute myeloid leukaemia.
Action
Description: Pyrimethamine is an antiparasitic agent. It impairs the protein synthesis and nuclear division of susceptible parasites through the inhibition of the dihydrofolate reductase enzyme. Pharmacokinetics: Absorption: Almost completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: 2-6 hours. Distribution: Mainly distributed in the kidneys, lungs, liver, and spleen. Crosses placenta and enters breast milk. Volume of distribution: 2.9 L/kg. Plasma protein binding: Approx 80-90%. Metabolism: Metabolised in the liver. Excretion: Via urine (16-32%). Elimination half-life: Approx 96 hours.
Chemical Structure
Pyrimethamine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4993, Pyrimethamine. https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimethamine. Accessed Oct. 27, 2020.
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