When we think about medications that cause hyperkalemia (elevated potassium), ACE inhibitors, ARBs, and spironolactone usually come to mind. However, several other medications can increase potassium levels and are easy to overlook in clinical practice.
Here are three important medications to remember.
1. Trimethoprim in Bactrim
Bactrim (sulfamethoxazole/trimethoprim) is a commonly prescribed antibiotic that can cause clinically significant hyperkalemia (excellent board exam nugget).
Trimethoprim acts similarly to amiloride by blocking epithelial sodium channels in the distal nephron. This reduces sodium reabsorption and decreases the electrical gradient that promotes potassium excretion into the urine.
Important clinical pearls:
- Hyperkalemia risk increases in patients with chronic kidney disease, diabetes, or older age.
- Combining trimethoprim with an ACE inhibitor, ARB, or spironolactone can significantly increase the risk.
- Hyperkalemia can develop even with standard doses, particularly in susceptible patients.
- Consider monitoring potassium and renal function in high-risk patients, especially when treatment extends beyond a short course.
Here was a wonderful case that was donated many years ago that is still a great lesson for today!
2. Finerenone (Kerendia)
Finerenone is a newer, nonsteroidal mineralocorticoid receptor antagonist used in selected patients with chronic kidney disease associated with type 2 diabetes and in certain patients with heart failure. Like spironolactone and eplerenone, finerenone blocks mineralocorticoid receptors. This reduces aldosterone-mediated effects and decreases potassium excretion by the kidneys.
Important clinical pearls:
- Patients with reduced kidney function and higher baseline potassium levels are at increased risk.
- Potassium and estimated glomerular filtration rate (eGFR) should be assessed before initiation, with follow-up potassium monitoring after starting treatment and after dose changes, according to prescribing guidance.
- Strong CYP3A4 inhibitors can increase finerenone exposure and are contraindicated with finerenone.
3. Tacrolimus
Tacrolimus is an immunosuppressant commonly used after organ transplantation and in selected other conditions. Although it is not usually the first medication clinicians think of when reviewing hyperkalemia, it can be an important contributor. Tacrolimus can impair renal potassium excretion through effects on kidney tubular function and aldosterone-related pathways. It can also contribute to renal dysfunction, further increasing the risk of elevated potassium.
Important clinical pearls:
- Hyperkalemia can occur even when tacrolimus concentrations are within the therapeutic range.
- Risk increases with impaired kidney function and concurrent medications that raise potassium.
- ACE inhibitors, ARBs, potassium supplements, and potassium-sparing diuretics can add to the risk.
- Monitor potassium and renal function in patients receiving tacrolimus, particularly after medication changes or when kidney function worsens.
If you are looking for more on tacrolimus, check out this podcast episode.
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