Sulphonamide + Folate Synthesis Inhibitor Combination Pregnancy: Avoid — trimethoprim is a folate antagonist (neural tube defects risk in first trimester); sulphonamide causes neonatal haemolysis and kernicterus in third trimester. Use in second trimester only if essential with high-dose folic acid 5mg OD.

Co-trimoxazole (Trimethoprim + Sulfamethoxazole)

Brand names: Septrin

Adult dose

Dose: UTI (acute): 960mg (2 standard tablets) BD for 7 days (check local resistance — E. coli resistance >20% in many areas). Pneumocystis jirovecii pneumonia (PCP) treatment: 120mg/kg/day IV/oral in 2–4 divided doses for 21 days. PCP prophylaxis (HIV, immunocompromised): 960mg OD or 960mg 3 times per week. Toxoplasmosis prophylaxis: 960mg OD.

Route: Oral / IV

Frequency: Twice daily (most indications); once daily or alternate days (prophylaxis)

Max: 4320mg daily (PCP treatment — high dose)

Standard tablet: trimethoprim 80mg + sulfamethoxazole 400mg = 480mg. Double-strength tablet: 960mg. Folate antagonism — avoid prolonged use without folinic acid supplementation. Not for use as first-line UTI treatment in pregnancy (congenital anomalies — trimethoprim is folate antagonist) or in third trimester (neonatal haemolysis — sulphonamide).

Paediatric dose

Dose: 6 mg/kg

Route: Oral / IV

Frequency: Twice daily

Max: 960mg BD (standard dosing)

BNFc: 6 weeks–5 months: 120mg BD. 6 months–5 years: 240mg BD. 6–11 years: 480mg BD. 12–17 years: 960mg BD. PCP treatment and prophylaxis: doses higher — seek specialist paediatric infectious disease opinion.

Dose adjustments

Renal

eGFR 15–30: standard dose for 3 days, then half dose. eGFR <15: avoid (sulphonamide accumulation).

Hepatic

Severe hepatic impairment: avoid.

Paediatric weight-based calculator

Patient weight (kg)

Clinical pearls

Hyperkalaemia: trimethoprim blocks renal tubular potassium secretion (structurally similar to amiloride) — monitor potassium in patients on ACE inhibitors, ARBs, or potassium supplements; can cause life-threatening hyperkalaemia
PCP prophylaxis: most important indication today — all HIV patients with CD4 <200 cells/microL should receive PCP prophylaxis (co-trimoxazole 960mg OD or 3×/week); also for immunosuppressed transplant and oncology patients
SJS/TEN risk: highest in HIV-positive patients (up to 50× higher than immunocompetent) — monitor closely; any rash: stop immediately
Local resistance: check local antibiogram before using for UTI — E. coli resistance is high (>20%) in many UK areas; trimethoprim alone or nitrofurantoin preferred if resistance rates are high

Contraindications

Sulphonamide or trimethoprim hypersensitivity
Severe renal impairment (eGFR <15)
Severe hepatic impairment
Blood dyscrasias
First trimester and third trimester of pregnancy

Side effects

Nausea, vomiting, diarrhoea
Rash — including Stevens-Johnson syndrome / TEN (rare — particularly with HIV)
Folate deficiency, megaloblastic anaemia (prolonged use)
Hyperkalaemia (trimethoprim blocks potassium excretion — as an aldosterone antagonist-like effect)
Nephrotoxicity (crystalluria)
Thrombocytopenia, agranulocytosis (rare)
Photosensitivity

Interactions

Warfarin — markedly increases INR (CYP2C9 inhibition); reduce warfarin dose and monitor INR
Methotrexate — additive folate antagonism; severe toxicity risk — avoid combination
ACE inhibitors / potassium-sparing diuretics — additive hyperkalaemia (trimethoprim's potassium-sparing effect)
Phenytoin — increases phenytoin levels (CYP2C9 inhibition)

Monitoring

FBC (agranulocytosis, thrombocytopenia — particularly if prolonged use)
U&E and potassium (hyperkalaemia — particularly with ACE inhibitors)
Renal function
Rash surveillance

Reference: BNFc; BNF 90; BHIVA HIV Guidelines 2023; NICE NG112 (UTI); NICE HIV Management Guidelines. Verify against your local formulary and the latest BNF before prescribing.

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