pyrimethamine: clinical use

Prescribing considerations

• Use only as combination therapy for licensed toxoplasmosis indications.
• Co-prescribe calcium folinate; folic acid does not reliably reverse folate deficiency caused by dihydrofolate-reductase inhibition.
• Review the companion anti-infective's contraindications, cautions and interactions.
• Ensure adequate hydration when a sulfonamide is used.
• Use cautiously in hepatic or renal impairment and in people with a seizure history.

Contraindications and cautions

• Hypersensitivity to pyrimethamine or a formulation excipient
• Generally avoid during the first trimester unless the expected benefit outweighs the risk
• Avoid breastfeeding during toxoplasmosis treatment
• Contains lactose and is unsuitable for specified rare hereditary disorders of galactose metabolism

Monitoring

• Obtain and monitor full blood counts during treatment and after it ends.
• More frequent blood counts are required in immunosuppressed patients.
• Stop treatment and provide calcium folinate if clinical or laboratory evidence of folate deficiency develops.
• Monitor for rash, infection, bleeding, anaemia and neurological effects.

Clinical pharmacology

Pyrimethamine competitively inhibits protozoal dihydrofolate reductase. It is almost completely absorbed orally, is highly protein-bound, undergoes predominantly hepatic metabolism and has a long elimination half-life. It crosses the placenta and is distributed into breast milk.

Formulation and product differences

• The selected product is an oral, white, round tablet supplied in child-resistant blister packaging.
• It contains lactose and is essentially sodium-free.
• No alternative pyrimethamine formulation is represented by the selected SmPC.