A fixed-dose combination of a dihydrofolate reductase inhibitor (Pyrimethamine) and a long-acting sulfonamide (Sulphadoxine) used primarily for the prophylaxis and treatment of chloroquine-resistant Plasmodium falciparum malaria. It is also used for the treatment of Toxoplasmosis. The combination acts synergistically by sequential blockade of the folate synthesis pathway in protozoan parasites.
Adult: For Malaria Prophylaxis: One tablet (12.5mg/250mg) once weekly. Start 1-2 weeks before entering endemic area, continue weekly during stay, and for 4-6 weeks after leaving. For Malaria Treatment (if susceptible): A single dose of 3 tablets (total Pyrimethamine 37.5mg + Sulphadoxine 750mg) as a single dose. NOTE: ACTs are first-line for treatment in India.
Note: Administer orally with a full glass of water after meals to minimize GI upset. For weekly prophylaxis, take on the same day each week. Maintain adequate fluid intake to prevent crystalluria. Folinic acid (leucovorin) 5-15 mg daily may be co-administered during prolonged therapy to mitigate hematological toxicity.
The combination provides a sequential, synergistic blockade of the folate synthesis pathway in susceptible protozoa. Sulphadoxine competitively inhibits dihydropteroate synthase (DHPS), preventing the conversion of para-aminobenzoic acid (PABA) to dihydropteroate. Pyrimethamine selectively and potently inhibits parasite dihydrofolate reductase (DHFR), preventing the conversion of dihydrofolate to tetrahydrofolate. This dual blockade depletes tetrahydrofolate, a cofactor essential for the synthesis of purines, pyrimidines, and certain amino acids, leading to inhibition of DNA/RNA synthesis and parasite death.
Pregnancy: Category C (US FDA). Pyrimethamine is teratogenic in animals at high doses. Sulfadoxine may cause kernicterus in the newborn. Use during pregnancy, especially first trimester, is contraindicated unless the potential benefit justifies the potential risk to the fetus (e.g., life-threatening toxoplasmosis). Folinic acid supplementation is essential.
Driving: May cause dizziness, headache, or visual disturbances. Patients should be cautioned about operating machinery or driving until their response is known.
| Warfarin/Acenocoumarol | Sulfadoxine may displace warfarin from protein binding, increasing anticoagulant effect and risk of bleeding. | Major |
| Phenytoin | Sulfadoxine may inhibit metabolism, increasing phenytoin levels and risk of toxicity (nystagmus, ataxia). | Major |
| Methotrexate | Additive antifolate effect; dramatically increases risk of bone marrow suppression and hepatotoxicity. | Contraindicated |
| Zidovudine (AZT) | Increased risk of hematological toxicity (anemia, neutropenia). | Major |
| Cyclosporine | Sulfadoxine may reduce cyclosporine levels, risking transplant rejection. | Moderate |
| Oral Hypoglycemics (Sulfonylureas) | Sulfadoxine may potentiate hypoglycemic effect. | Moderate |
| Probenecid | May decrease renal excretion of sulfadoxine, increasing its blood levels and toxicity risk. | Moderate |
| Folic Acid | May antagonize the antiprotozoal effect of pyrimethamine. Use folinic acid (leucovorin) instead for rescue therapy. | Major |
Same composition (Pyrimethamine (12.5mg) + Sulphadoxine (250mg)), different brands: