Causality assessment · Causality: well established

Trimethoprim (and co-trimoxazole) and Hyperkalaemia: is the FAERS signal real?

n=213 co-reports · PRR 11.0 · ROR 11.2

Trimethoprim (and co-trimoxazole) side-effect profile All assessments See in the full list

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Causality: well established

Trimethoprim (and co-trimoxazole) ↔ Hyperkalaemia

n=213 co-reports · PRR 11.0 · ROR 11.2

Trimethoprim blocks the epithelial sodium channel in the distal nephron in a way that resembles the potassium-sparing diuretics amiloride and triamterene, so it reduces urinary potassium excretion and can raise serum potassium — an effect that is easy to overlook because trimethoprim is prescribed mainly as an antibiotic. The risk is greatest at higher doses, in older patients, in renal impairment, and with coexisting ACE inhibitors, ARBs, or spironolactone. The 213 co-reports (PRR 11.0) reflect both a genuine effect and the drug's very wide short-course use.

Regulatory basis: trimethoprim/co-trimoxazole prescribing information (hyperkalaemia caution, especially with RAAS blockade).

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Potassium rises during treatment and falls after withdrawal
Strength	met	PRR 11 on a modest co-report count
Consistency	met	Reproduced in controlled studies and cohort data, notably in older patients on RAAS blockade
Specificity	met	A fairly distinctive effect of trimethoprim among antibacterials
Biological gradient	met	Dose-related and worse with renal impairment, age, and RAAS-blocking drugs
Plausibility	met	Distal-nephron sodium-channel blockade mimics potassium-sparing diuretics
Coherence	met	Coheres with the labelled hyperkalaemia caution and electrolyte monitoring
Experiment	partial	Controlled studies of co-trimoxazole versus other antibiotics support it; no large dedicated RCT
Analogy	met	Analogous to amiloride/triamterene potassium retention

This page's own qualitative read, not an automated/citation-gated assessment.

✗ No ClinicalTrials.gov results-posting trial in the top search hits for trimethoprim captured hyperkalaemia; the effect is a monitored biochemistry finding rather than a coded trial endpoint, and is established from prescribing information, controlled studies, and cohorts.