Sulfadoxinepyrimethamine

Sulfadoxine-pyrimethamine, commonly known as SP, is a fixed-dose combination antimalarial medication consisting of sulfadoxine and pyrimethamine. It has been used both to treat uncomplicated malaria and to prevent malaria in high-transmission areas.

Mechanism of action: Sulfadoxine inhibits dihydropteroate synthase, while pyrimethamine inhibits dihydrofolate reductase. The two actions block sequential steps in the parasite’s folate synthesis pathway, disrupting DNA synthesis and parasite replication. Their combined effect makes SP effective against Plasmodium species in regions with some sensitivity to the drug.

Indications and use: SP is used for treating uncomplicated Plasmodium falciparum malaria in areas where the parasite remains susceptible. It is also used for intermittent preventive treatment in pregnancy (IPTp) and infants (IPTi) in malaria-endemic regions, sometimes as part of broader preventive strategies. Because resistance to SP is widespread in many areas, SP is not always the first-line treatment for malaria and is often employed in combination with other antimalarials or in specific preventive regimens.

Administration and dosing: The medication is taken orally as fixed-dose tablets. Dosing regimens depend on the indication and regional guidelines; for IPTp, SP may be given as a single-dose regimen during the second or third trimester and repeated at intervals, according to local recommendations. SP can be used alongside other antimalarial therapies in treatment regimens where recommended.

Safety, contraindications, and resistance: Common side effects include gastrointestinal upset and rash; hypersensitivity to sulfonamides is a concern. Pyrimethamine can cause bone marrow suppression, so folate supplementation considerations may apply. SP is contraindicated in certain sulfonamide allergies and requires caution in pregnancy, certain blood disorders, and high-resistance areas. Widespread resistance due to mutations in the DHPS and DHFR enzymes has limited SP’s effectiveness as a frontline treatment, prompting continued use primarily in combination therapies and preventive programs in specific settings.