Pharmacology · 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
Enzyme: Bacterial dihydrofolate reductase
ATC code: J01EA01
WHO Model List of Essential Medicines

Bacterial dihydrofolate reductaseTrimethoprim

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

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) →

Adverse effects

Common

Itching and rash
Nausea and stomach upset
Altered taste

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.

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)

Urinary tract infection (acute cystitis)

← Back to the class: 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 (DailyMed (U.S. National Library of Medicine), 2026); Trimethoprim: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025); S. aureus DHFR complexed with NADPH and TMP (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.