[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Antimalarials](https://durgical.com/en/pharmacology/classes/antimalarials/) › Sulfadoxine–pyrimethamine # Sulfadoxine–pyrimethamine ## Antimalarials? Antimalarials ## Pregnancy: avoid? Avoid in the first trimester. From the second trimester WHO recommends it for preventive treatment in moderate- to high-transmission areas of Africa, and the last dose can be… Fixed folate-blocking antimalarial combination, now used mostly to prevent malaria in pregnancy and in children in Africa, not for treatment. Updated Nov 12, 2026 Also called: SP ## Quick facts **Group** [Antimalarials](https://durgical.com/en/pharmacology/classes/antimalarials/) **Target** Plasmodium dihydropteroate synthase (sulfadoxine) and dihydrofolate reductase (pyrimethamine) **Used for** Intermittent preventive treatment **Key effects** Nausea · Rash **Monitor** Rash · In pregnancy **ATC** P01BD51 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Clinical What the labels mean - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ✂**Plasmodium dihydropteroate synthase (sulfadoxine) and dihydrofolate reductase (pyrimethamine)**Sulfadoxine–pyrimethamine ⓘ The figure shows pyrimethamine bound to dihydrofolate reductase of Plasmodium vivax; sulfadoxine acts one step earlier, on dihydropteroate synthase. **Target in 3D:** Plasmodium dihydropteroate synthase (sulfadoxine) and dihydrofolate reductase (pyrimethamine). PDB structure 2BL9 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/2BL9) · Drag to rotate · pinch to zoom The parasite must make its own folate to build DNA. Sulfadoxine, a long-acting sulfonamide, competes with para-aminobenzoic acid at dihydropteroate synthase; pyrimethamine blocks the parasite's dihydrofolate reductase much more than the human enzyme. Blocking two steps of the same pathway in sequence gives a synergistic effect. Mutations in both enzymes have spread widely, which is why the combination is no longer used to treat malaria on its own. - Sulfadoxine blocks dihydropteroate synthase (competes with PABA) - Pyrimethamine blocks the parasite's dihydrofolate reductase - Two steps of folate synthesis stop in sequence - Without folate the parasite cannot copy its DNA ## Indications - Intermittent preventive treatment of malaria in pregnancy (IPTp) in areas of moderate to high transmission in Africa, from the second trimester [Malaria →](https://durgical.com/en/conditions/malaria/) - Seasonal malaria chemoprevention in children, combined with amodiaquine [Malaria →](https://durgical.com/en/conditions/malaria/) - Partner of artesunate in an artemisinin-based combination for treatment in some regions [Malaria →](https://durgical.com/en/conditions/malaria/) ## Adverse effects ### Common - Nausea, vomiting, weakness and dizziness, mostly with the first dose - Rash ### Serious (rare, important) - Severe skin reactions (Stevens–Johnson syndrome, toxic epidermal necrolysis), as with other sulfonamides: rare, and deaths from sulfonamide hypersensitivity have been reported ## Contraindications - Allergy to sulfonamides or pyrimethamine - Women already receiving co-trimoxazole prophylaxis (as in HIV): IPTp-SP is not given - First trimester of pregnancy ## Key interactions **Co-trimoxazole (sulfamethoxazole–trimethoprim)** The same two-step folate blockade: no added benefit and worse adverse reactions, so they are not given together. **High-dose folic acid** Counteracts the antimalarial effect; only the low daily dose used in routine antenatal care is combined with SP. ## What is monitored - Rash, blisters or mouth sores, which mean stopping at once - New skin lesions at any time after a dose - In pregnancy, attendance at each antenatal visit and the interval between doses ## Administration and safety - Oral, ideally as directly observed treatment at the antenatal or community visit - Doses for IPTp are spaced at least one month apart - Not given in the first trimester, nor with co-trimoxazole prophylaxis ## Pregnancy and breastfeeding Avoid in the first trimester. From the second trimester WHO recommends it for preventive treatment in moderate- to high-transmission areas of Africa, and the last dose can be given up to delivery. ## Nursing care - Ask about sulfonamide allergy and co-trimoxazole use before each dose - Check the gestational age (from the second trimester only) - Give the low-dose folic acid of routine care, not high-dose folic acid - Teach to report rash, blisters or mouth sores immediately - Promote insecticide-treated nets: SP does not replace them ## Pharmacokinetics **Absorption** Oral; it can be taken with or without food. **Elimination** Both components are long-acting, which allows single, spaced doses for prevention. ## Memory aid «Two locks on one door»: sulfadoxine locks the first folate step, pyrimethamine the next; adding co-trimoxazole only adds a third copy of the same lock (and its toxicity). ## Test yourself Think of the answer, then tap the question to see it. ## Which two enzymes of the parasite's folate pathway does sulfadoxine–pyrimethamine block? Dihydropteroate synthase (sulfadoxine) and dihydrofolate reductase (pyrimethamine). ## What is the main current use of sulfadoxine–pyrimethamine? Prevention: intermittent preventive treatment in pregnancy in Africa and, with amodiaquine, seasonal chemoprevention in children. ## Why should a pregnant woman with HIV on co-trimoxazole prophylaxis not receive IPTp-SP? Both block the same folate steps, so there is no extra benefit and adverse reactions worsen. ## Which folic acid supplement can be combined with SP in pregnancy? Only the low daily dose of routine antenatal care; high doses counteract the antimalarial effect. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/sulfadoxine-pyrimethamine/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## What the labels mean **Pregnancy: avoid** Avoid in the first trimester. From the second trimester WHO recommends it for preventive treatment in moderate- to high-transmission areas of Africa, and the last dose can be… ## Connections ## Related drugs 4 - [Pyrimethamine](https://durgical.com/en/pharmacology/pyrimethamine/) - [Sulfadiazine](https://durgical.com/en/pharmacology/sulfadiazine/) - [Sulfamethoxazole + trimethoprim (co-trimoxazole)](https://durgical.com/en/pharmacology/sulfamethoxazole-trimethoprim/) - [Artesunate](https://durgical.com/en/pharmacology/artesunate/) ## Related conditions 1 - [Malaria](https://durgical.com/en/conditions/malaria/) [← Back to the class: Antimalarials](https://durgical.com/en/pharmacology/classes/antimalarials/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [WHO policy brief for the implementation of intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP)](https://www.afro.who.int/sites/default/files/2017-06/iptp-sp-updated-policy-brief-24jan2014.pdf) (World Health Organization (WHO), 2014); [Seasonal malaria chemoprevention with sulfadoxine–pyrimethamine plus amodiaquine in children: a field guide](https://www.who.int/publications/i/item/9789240073692) (World Health Organization (WHO), 2023); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/?query=sulfadoxine) (World Health Organization (WHO), 2026); [DailyMed - SULFADIAZINE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8993651b-fff6-4e3f-9b60-78587bc9bcee) (DailyMed (U.S. National Library of Medicine), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/sulfadoxine-pyrimethamine/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/sulfadoxine-pyrimethamine/