sulfadoxine

Sulfadoxine is a long-acting sulfonamide antimicrobial agent used primarily in combination with pyrimethamine for the treatment and prevention of malaria. It inhibits dihydropteroate synthase, an enzyme in the parasite folate synthesis pathway, thereby blocking DNA synthesis. When paired with pyrimethamine, which inhibits dihydrofolate reductase, the combination produces a synergistic blockade of folate metabolism in Plasmodium species.

Clinical use centers on malaria treatment in regions with susceptible parasite strains and on malaria prevention strategies. Sulfadoxine-pyrimethamine (SP) has been used to treat uncomplicated Plasmodium falciparum malaria and, in some areas, P. vivax malaria. Its effectiveness is limited by widespread resistance due to mutations in parasite dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR). SP remains a component of intermittent preventive treatment in pregnancy (IPTp) and, in certain guidelines, intermittent preventive treatment in infants (IPTi), often as a single-dose regimen administered during routine antenatal visits or vaccination campaigns. In many settings, SP is no longer preferred for treating malaria due to resistance and is restricted to preventive uses in others.

Pharmacokinetics and administration are oral, with a long half-life that supports single-dose preventive regimens but can contribute to selection of resistant parasites. It is usually given in fixed-dose combinations with pyrimethamine. Metabolism occurs in the liver with renal excretion.

Safety and resistance: adverse effects can include hypersensitivity reactions, rash, and hematologic effects such as megaloblastic anemia related to folate deficiency; severe reactions are rare but possible. Folate supplementation can diminish the efficacy of SP, and caution is advised in pregnancy, sulfonamide allergy, or folate-deficient individuals. Regulatory status varies by country, with many guidelines limiting SP to preventive use in malaria-endemic areas and preferring other therapies for treatment where resistance is high.