NutriStack
Potassium and Trimethoprim-Sulfamethoxazole, a caution.
Trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, acting similarly to potassium-sparing diuretics like amiloride. Co-administration with potassium supplements can cause clinically significant hyperkalemia, particularly in older adults, patients with renal impairment, or those on ACE inhibitors, ARBs, or spironolactone. Severe hyperkalemia can cause cardiac arrhythmias and sudden death.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
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At a glance
- Substances
- Potassium and Trimethoprim-Sulfamethoxazole
- Pair type
- Caution
- Evidence (highest tier)
- Strong
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Strong evidence
Caution
What is happening. Trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, acting similarly to potassium-sparing diuretics like amiloride. Co-administration with potassium supplements can cause clinically significant hyperkalemia, particularly in older adults, patients with renal impairment, or those on ACE inhibitors, ARBs, or spironolactone. Severe hyperkalemia can cause cardiac arrhythmias and sudden death.
Mechanism. Trimethoprim blocks the amiloride-sensitive epithelial sodium channel (ENaC) in the collecting duct, reducing sodium reabsorption and decreasing the electrochemical gradient that drives potassium secretion. The net effect is potassium retention.
Recommendation. Avoid routine potassium supplementation during trimethoprim-sulfamethoxazole therapy unless directed by a clinician. If supplementation is necessary, monitor serum potassium closely, particularly in older adults or patients with kidney disease.
Sources (3)
- Chan WY, Clark AB, Wilson AM, Loke YK, TIPAC investigators. The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial. Br J Clin Pharmacol. 2017;83(8):1808-1814. PMID 28192629
- Antoniou T, Hollands S, Macdonald EM, Gomes T, Mamdani MM, Juurlink DN. Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ. 2015;187(4):E138-E143. PMID 25646289
- Crellin E, Mansfield KE, Leyrat C, et al. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study. BMJ. 2018;360:k341. PMID 29438980
Stack Score
How this pair moves the number.
Effect on the composite score
If both Potassium and Trimethoprim-Sulfamethoxazole are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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