Pharmacology · Sulfonamides and trimethoprim

Sulfadiazine !

A sulfonamide that reaches the brain well; with pyrimethamine it is the classic treatment of toxoplasmosis, including in HIV.

Updated 2026-11-01

Class: Sulfonamides and trimethoprim
Enzyme: Dihydropteroate synthase (bacterial and Toxoplasma folate pathway)
ATC code: J01EC02
WHO Model List of Essential Medicines

Dihydropteroate synthase (bacterial and Toxoplasma folate pathway)Sulfadiazine

The figure shows sulfamethoxazole, a closely related sulfonamide that occupies the same PABA pocket, in dihydropteroate synthase of Yersinia pestis.

Target in 3D: Dihydropteroate synthase (bacterial and Toxoplasma folate pathway). PDB structure 3TZF (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Sulfadiazine competes with para-aminobenzoic acid at dihydropteroate synthase, so the microbe makes less dihydrofolate. Pyrimethamine blocks the next enzyme, dihydrofolate reductase, in Toxoplasma, giving a sequential block of folate synthesis.

Diffuses into tissues and the cerebrospinal fluid
Competes with PABA at dihydropteroate synthase
Folate synthesis falls (more with pyrimethamine)
The parasite or bacterium cannot make DNA

Pharmacokinetics

Absorption: Well absorbed by mouth.
Distribution: Enters the cerebrospinal fluid well; crosses the placenta and reaches breast milk.
Elimination: Urine; crystals can form in acid, concentrated urine.

Indications

Toxoplasmic encephalitis in people with and without HIV, with pyrimethamine HIV infection and AIDS →
Prevention of rheumatic fever recurrences as an alternative to penicillin Rheumatic heart disease →
Congenital toxoplasmosis, with pyrimethamine

Adverse effects

Common

Nausea, vomiting and loss of appetite
Rash and fever
Photosensitivity

Contraindications

Allergy to sulfonamides
Infants under 2 months, except with pyrimethamine for congenital toxoplasmosis
Pregnancy at term and breastfeeding (kernicterus risk)

Key interactions

Pyrimethamine: Synergy against Toxoplasma, but more folate depletion and marrow suppression.
Oral anticoagulants and methotrexate: Their effects may increase, as the sulfonamide displaces them from albumin.

What is monitored

Urine output and urinalysis for crystals
Full blood count
Skin for rash

Administration and safety

Plenty of fluid is given to keep urine output high and avoid crystals
Given by mouth

Nursing care

Encourage fluids and measure urine output
Teach to report rash, sore throat, fever or blood in the urine
Ask about sulfa allergy

Pregnancy and breastfeeding

Its safe use in pregnancy is not established, and it is avoided at term because it can cause kernicterus.

Test yourself

Think of the answer, then tap the question to see it.

Which drug is sulfadiazine combined with for toxoplasmosis?

Pyrimethamine.

Why is high fluid intake important with sulfadiazine?

It can crystallise in concentrated urine and cause stones and kidney injury.

Why is it avoided at term?

Sulfonamides displace bilirubin and can cause kernicterus in the newborn.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - SULFADIAZINE tablet (DailyMed (U.S. National Library of Medicine), 2026); Sulfadiazine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).

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Representative model, for educational purposes only.