Pharmacology · 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
Also called: co-trimoxazole, TMP-SMX
The figure shows sulfamethoxazole in dihydropteroate synthase of Yersinia pestis, the first enzyme the pair blocks.
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) →
- Prevention and treatment of Pneumocystis jirovecii pneumonia in people with HIV and other immunosuppressed patients 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
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.
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.
Related drugs
Related conditions
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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 - SULFAMETHOXAZOLE AND TRIMETHOPRIM tablet (DailyMed (U.S. National Library of Medicine), 2026); Co-trimoxazole: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025); Crystal Structure of the Yersinia pestis Dihydropteroate Synthase with Sulfonamide Drug Complex. (RCSB Protein Data Bank, 2026).
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Representative model, for educational purposes only.