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
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.

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

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 →
Seasonal malaria chemoprevention in children, combined with amodiaquine Malaria →
Partner of artesunate in an artemisinin-based combination for treatment in some regions Malaria →

Adverse effects

Common

Nausea, vomiting, weakness and dizziness, mostly with the first dose
Rash

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.

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.

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Connections

← Back to the class: 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) (World Health Organization (WHO), 2014); Seasonal malaria chemoprevention with sulfadoxine–pyrimethamine plus amodiaquine in children: a field guide (World Health Organization (WHO), 2023); eEML - Electronic Essential Medicines List (World Health Organization (WHO), 2026); DailyMed - SULFADIAZINE tablet (DailyMed (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.