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

# Trimethoprim

A dihydrofolate reductase inhibitor used alone for cystitis and as the partner in co-trimoxazole. It can raise potassium.

Updated 2026-11-01

- Class: [Sulfonamides and trimethoprim](https://durgical.com/en/pharmacology/classes/sulfonamides-and-trimethoprim/)
- Enzyme: Bacterial dihydrofolate reductase
- ATC code: J01EA01
- WHO Model List of Essential Medicines

✂**Bacterial dihydrofolate reductase**Trimethoprim

ⓘ The figure shows trimethoprim and the cofactor NADPH bound to dihydrofolate reductase of Staphylococcus aureus.

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

## Mechanism of action

Trimethoprim binds bacterial dihydrofolate reductase far more tightly than the human enzyme and stops dihydrofolate from becoming tetrahydrofolate. Without tetrahydrofolate the bacterium cannot make thymidine and purines, and growth stops.

- Absorbed and concentrated in the urine
- Binds bacterial dihydrofolate reductase
- Tetrahydrofolate is not made
- DNA synthesis and growth stop

## Pharmacokinetics

**Absorption**
Well absorbed by mouth.

**Elimination**
Kidney, by filtration and tubular secretion; high urinary levels.

**Half-life**
About 8–10 hours.

## Indications

- Uncomplicated urinary tract infections due to susceptible bacteria (WHO «Access» antibiotic) [Urinary tract infection (acute cystitis) →](https://durgical.com/en/conditions/urinary-tract-infection/)

## Adverse effects

### Common

- Itching and rash
- Nausea and stomach upset
- Altered taste

### Serious (rare, important)

- Hyperkalaemia, especially in older adults and kidney disease
- Megaloblastic anaemia, low platelets or white cells (folate antagonism)
- Severe skin reactions (rare)

## Contraindications

- Allergy to trimethoprim
- Megaloblastic anaemia due to folate deficiency

## Key interactions

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

**Phenytoin**
Phenytoin levels may rise.

**Serum methotrexate tests**
Trimethoprim can interfere with some methotrexate assays.

## What is monitored

- Potassium and creatinine in older adults and kidney disease
- Full blood count in long courses or folate deficiency

## Administration and safety

- Given by mouth
- Kidney function guides dose selection, especially in older adults

## Nursing care

- Teach to report sore throat, fever, pallor or bruising
- Check potassium in at-risk patients
- Ask about folate deficiency risks (pregnancy, alcohol use, malnutrition)

## Pregnancy and breastfeeding

It is a folate antagonist and was teratogenic in rats at high doses; it is used in pregnancy only if the benefit justifies the risk.

## Memory aid

«TMP = The Middle Path of folate»: it blocks the step in the middle, from DHF to THF.

## Test yourself

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

## Which enzyme does trimethoprim inhibit?

Bacterial dihydrofolate reductase.

## Which electrolyte disturbance can it cause?

Hyperkalaemia.

## In which anaemia is it contraindicated?

Megaloblastic anaemia due to folate deficiency.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/trimethoprim/)

## Related drugs

- [Sulfamethoxazole + trimethoprim (co-trimoxazole)](https://durgical.com/en/pharmacology/sulfamethoxazole-trimethoprim/)
- [Nitrofurantoin](https://durgical.com/en/pharmacology/nitrofurantoin/)

## Related conditions

- [Urinary tract infection (acute cystitis)](https://durgical.com/en/conditions/urinary-tract-infection/)

[← 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 - TRIMETHOPRIM tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=249e938d-f181-47c4-a082-372d65462f33) (DailyMed (U.S. National Library of Medicine), 2026); [Trimethoprim: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a684025.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/?query=trimethoprim) (World Health Organization, 2025); [S. aureus DHFR complexed with NADPH and TMP](https://www.rcsb.org/structure/3FRE) (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.

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