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[Pharmacology](https://durgical.com/en/pharmacology/) · [Sulfonamides and trimethoprim](https://durgical.com/en/pharmacology/classes/sulfonamides-and-trimethoprim/)

# Sulfamethoxazole + trimethoprim (co-trimoxazole)

Two antifolates in one tablet. Key for preventing and treating Pneumocystis, for urinary infections, toxoplasmosis and shigellosis.

Updated 2026-11-01

- Class: [Sulfonamides and trimethoprim](https://durgical.com/en/pharmacology/classes/sulfonamides-and-trimethoprim/)
- Enzyme: Dihydropteroate synthase (sulfamethoxazole) and dihydrofolate reductase (trimethoprim)
- ATC code: J01EE01
- WHO Model List of Essential Medicines

Also called: co-trimoxazole, TMP-SMX

✂**Dihydropteroate synthase (sulfamethoxazole) and dihydrofolate reductase (trimethoprim)**Sulfamethoxazole + trimethoprim (co-trimoxazole)

ⓘ The figure shows sulfamethoxazole in dihydropteroate synthase of Yersinia pestis, the first enzyme the pair blocks.

**Target in 3D:** Dihydropteroate synthase (sulfamethoxazole) and dihydrofolate reductase (trimethoprim). PDB structure 3TZF (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/3TZF) · Drag to rotate · pinch to zoom

## Mechanism of action

Sulfamethoxazole competes with para-aminobenzoic acid (PABA) at dihydropteroate synthase, so the bacterium makes less dihydrofolic acid. Trimethoprim then blocks bacterial dihydrofolate reductase, the step to tetrahydrofolic acid. Two consecutive blocks starve the cell of the folate it needs for thymidine and purines.

- Sulfamethoxazole competes with PABA at dihydropteroate synthase
- Less dihydrofolic acid is made
- Trimethoprim blocks dihydrofolate reductase
- No tetrahydrofolate: DNA building blocks run out

## Pharmacokinetics

**Absorption**
Both parts are well absorbed by mouth, peak in one to four hours; an IV form exists.

**Distribution**
Sputum, vaginal and middle-ear fluid; both cross the placenta and reach breast milk.

**Metabolism**
Sulfamethoxazole is acetylated and conjugated in the liver.

**Elimination**
Urine, by filtration and tubular secretion.

**Half-life**
About 10 hours (sulfamethoxazole) and 8–10 hours (trimethoprim).

## Indications

- Urinary tract infections caused by susceptible bacteria [Urinary tract infection (acute cystitis) →](https://durgical.com/en/conditions/urinary-tract-infection/)
- Prevention and treatment of Pneumocystis jirovecii pneumonia in people with HIV and other immunosuppressed patients [HIV infection and AIDS →](https://durgical.com/en/conditions/hiv-infection-and-aids/)
- Toxoplasmosis treatment and prevention (WHO list)
- Shigellosis and traveller's diarrhoea due to susceptible strains

## Adverse effects

### Common

- Nausea, vomiting and loss of appetite
- Rash and itching
- Photosensitivity

### Serious (rare, important)

- Stevens–Johnson syndrome, toxic epidermal necrolysis and DRESS
- Hyperkalaemia, especially with high doses, kidney failure or other potassium-raising drugs
- Bone-marrow suppression, thrombocytopenia and haemolysis in G6PD deficiency
- Crystalluria and kidney injury; hepatitis; C. difficile colitis

## Contraindications

- Allergy to sulfonamides or trimethoprim
- Megaloblastic anaemia due to folate deficiency; previous drug-induced immune thrombocytopenia
- Infants under 2 months
- Marked liver damage; severe kidney failure when kidney function cannot be monitored; use with dofetilide

## Key interactions

**Warfarin**
Prolongs the prothrombin time (CYP2C9); INR is checked.

**Phenytoin**
Its metabolism is slowed; levels rise.

**Methotrexate**
Higher free methotrexate and marrow toxicity; avoided.

**ACE inhibitors, ARBs, spironolactone**
Higher risk of hyperkalaemia.

**Dofetilide**
Contraindicated: dofetilide levels rise.

## What is monitored

- Potassium and creatinine, especially in older adults and kidney disease
- Full blood count in long courses
- Skin for rash; INR on warfarin

## Administration and safety

- Plenty of fluid is given to prevent crystals in the urine
- The IV form is diluted and infused slowly, never as a bolus or intramuscular injection
- Look-alike names: co-trimoxazole contains a sulfa drug, a common allergy

## Nursing care

- Ask about sulfa allergy
- Teach to stop and report any rash, mouth sores or skin peeling
- Encourage fluids
- Teach sun protection; check potassium

## Pregnancy and breastfeeding

Some studies link exposure in pregnancy with birth defects (neural tube, heart, urinary tract); it is used only when the benefit justifies the risk, as in Pneumocystis pneumonia.

## Memory aid

«Two locks on one door»: sulfa locks the first step of folate, trimethoprim the second, so the bacterium cannot get in.

## Test yourself

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

## Which two enzymes does co-trimoxazole block?

Dihydropteroate synthase (sulfamethoxazole) and dihydrofolate reductase (trimethoprim).

## Which electrolyte rises with co-trimoxazole?

Potassium, because trimethoprim reduces its excretion by the kidney.

## Which opportunistic infection does it prevent in advanced HIV?

Pneumocystis jirovecii pneumonia (and toxoplasmosis).

## Why is it avoided in infants under 2 months?

Sulfonamides displace bilirubin and can cause kernicterus.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/sulfamethoxazole-trimethoprim/)

## Related drugs

- [Trimethoprim](https://durgical.com/en/pharmacology/trimethoprim/)
- [Sulfadiazine](https://durgical.com/en/pharmacology/sulfadiazine/)

## Related conditions

- [Urinary tract infection (acute cystitis)](https://durgical.com/en/conditions/urinary-tract-infection/)
- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)

[← Back to the class: Sulfonamides and trimethoprim](https://durgical.com/en/pharmacology/classes/sulfonamides-and-trimethoprim/)

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 - SULFAMETHOXAZOLE AND TRIMETHOPRIM tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ef62512-0dc3-4821-9b60-6b375841c4c0) (DailyMed (U.S. National Library of Medicine), 2026); [Co-trimoxazole: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a684026.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/?query=trimethoprim) (World Health Organization, 2025); [Crystal Structure of the Yersinia pestis Dihydropteroate Synthase with Sulfonamide Drug Complex.](https://www.rcsb.org/structure/3TZF) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/sulfamethoxazole-trimethoprim/