Sulfonamide antibacterials · Anti-infectives
Trimethoprim-sulfamethoxazole
co-trimoxazole · TMP-SMX · Septra · Bactrim · Bactrim® · Septra®(brand names vary by market)
Two folate blocks in sequence, and a potassium you must not ignore.
Also: oral liquid, infusion
Mechanism
Sulfamethoxazole blocks dihydropteroate synthase and trimethoprim blocks dihydrofolate reductase: sequential blockade of the same pathway, which converts two bacteriostatic drugs into a bactericidal pair.
Indications
- Urinary tract infection
- Pneumocystis jirovecii pneumonia, treatment and prophylaxis
- Community-acquired MRSA skin infection
- Nocardiosis
- Stenotrophomonas infection
Formulations
Dosing concepts
Two very different dose bands
Urinary doses and Pneumocystis doses differ several-fold. The Pneumocystis regimen is weight-based and toxic in ways the urinary dose is not.
Renal impairment
Dose-adjusted, and the hyperkalemia risk rises steeply as clearance falls.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- ~90%
- Half-life
- Trimethoprim 8 to 10 h; sulfamethoxazole 9 to 11 h
- Elimination
- mixed: Both renally cleared with hepatic metabolism of the sulfonamide
- Protein binding
- ~44% and ~70% respectively
Adverse effects
- Rashcommon & seriousRanges from trivial to Stevens-Johnson syndrome; any mucosal involvement or blistering is an emergency.
- Hyperkalemiacommon & seriousTrimethoprim blocks the epithelial sodium channel like amiloride. Dangerous alongside RAAS blockade or spironolactone.
- Creatinine rise without true GFR changecommonTrimethoprim blocks tubular creatinine secretion. Recognising this prevents a needless AKI workup.
- Bone marrow suppressionserious
- Hyponatremiaserious
Contraindications & precautions
Contraindications
- Sulfonamide hypersensitivity
- Third trimester of pregnancy and infants under 2 months
- Severe hepatic or renal impairment
- Megaloblastic anemia from folate deficiency
Precautions
- Concurrent RAAS blockade, spironolactone or potassium supplements
- Warfarin
- G6PD deficiency
- Older adults
Interactions
- Warfarin + Trimethoprim-sulfamethoxazoleavoidOne of the highest-risk warfarin combinations: INRs of 6+ and hospitalization-grade bleeding are well documented.
- ACE inhibitors / ARBs + Potassium-sparing diuretics, K supplements, salt substitutescautionAdditive hyperkalemia, worst with renal impairment layered on top.
- Broad-spectrum antibiotics (any) + WarfarinmonitorModest INR rise, additive with any CYP effect of the specific agent.
Monitoring
Potassium
The most consequential and most missed effect · Within a few days in anyone on RAAS blockade or with CKD
Creatinine, interpreted knowing about the secretion block
To avoid mistaking an artefact for injury
INR in warfarin patients
One of the strongest warfarin interactions there is
Rash
Severe cutaneous reactions
Counselling points
- Drink plenty of fluids while taking it.
- Report any rash immediately, especially with mouth or eye soreness.
- If you take a blood thinner, we will check your levels during and after the course.
- Avoid potassium salt substitutes.
Clinical pearls
- An older patient on an ACE inhibitor who is given this for a urinary infection can arrive days later with a potassium of six and a raised creatinine. Both are predictable and both are this drug.
- The creatinine rise from blocked tubular secretion is not kidney injury. Urea, electrolytes and urine output are unchanged, and it reverses within days of stopping.
References & review
- Trimethoprim-sulfamethoxazole product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.