A fixed-dose combination of a dihydrofolate reductase inhibitor (Pyrimethamine) and a long-acting sulfonamide (Sulphadoxine). It acts synergistically to inhibit folate metabolism in susceptible protozoa, primarily used for the prophylaxis and treatment of chloroquine-resistant Plasmodium falciparum malaria. In India, its use is now largely restricted due to widespread resistance and the availability of more effective artemisinin-based combination therapies (ACTs).
Adult: For Malaria Treatment: A single dose of 3 tablets (75mg Pyrimethamine + 2250mg Sulphadoxine). For Malaria Prophylaxis: 1 tablet (25mg+750mg) once weekly, starting 1-2 weeks before travel, during stay, and for 4-6 weeks after leaving the endemic area. For Toxoplasmosis: Pyrimethamine 25-50 mg daily + Sulphadoxine 1-1.5g daily (as per specific regimen, often with folinic acid).
Note: Administer orally after meals with a full glass of water to minimize GI upset. For prophylaxis, take on the same day each week. Folinic acid (leucovorin) 5-15 mg daily is often co-adminered during prolonged therapy (e.g., for toxoplasmosis) to prevent hematological toxicity.
Synergistic sequential blockade of the folate biosynthesis pathway in protozoa. Sulphadoxine competitively inhibits dihydropteroate synthase (DHPS), preventing the conversion of PABA to dihydrofolic acid. Pyrimethamine selectively and potently inhibits protozoal dihydrofolate reductase (DHFR), preventing the conversion of dihydrofolic acid to tetrahydrofolic acid. This dual blockade depletes tetrahydrofolate, a cofactor essential for DNA and RNA synthesis, leading to parasitic death.
Pregnancy: Category C (US FDA). Pyrimethamine is a known teratogen in animals at high doses. Sulphadoxine may cause kernicterus in the newborn if used near term. Use only if the potential benefit justifies the potential risk to the fetus, such as in life-threatening chloroquine-resistant malaria or toxoplasmosis. Must be supplemented with folinic acid.
Driving: May cause dizziness or blurred vision. Patients should be cautioned about driving or operating machinery until their response is known.
| Warfarin | Sulphadoxine may displace warfarin from protein binding sites, potentiating anticoagulant effect and increasing INR risk. | Major |
| Phenytoin | Sulphadoxine may inhibit metabolism and displace phenytoin, increasing risk of phenytoin toxicity (ataxia, nystagmus). | Major |
| Methotrexate | Additive antifolate effect; dramatically increases risk of severe bone marrow suppression and hepatotoxicity. | Contraindicated |
| Zidovudine (AZT) | Increased risk of hematological toxicity (anemia, neutropenia). | Major |
| Cyclosporine | Increased risk of nephrotoxicity. | Moderate |
| Oral Hypoglycemics (Sulfonylureas) | Sulphadoxine may potentiate hypoglycemic effect via displacement from proteins. | Moderate |
| Probenecid | May decrease renal excretion of sulphadoxine, increasing its concentration and toxicity risk. | Moderate |
| Folic Acid (high dose) | May antagonize the antiprotozoal effect of pyrimethamine. Use folinic acid (leucovorin) instead for rescue therapy. | Moderate |
Same composition (Pyrimethamine (25mg) + Sulphadoxine (750mg)), different brands: