What is the significance of hyperkalemia when using Angiotensin-Converting Enzyme (ACE) inhibitors and Trimethoprim/Sulfamethoxazole (Bactrim)?

From the Guidelines

The combination of ACE inhibitors and Bactrim (trimethoprim-sulfamethoxazole) significantly increases the risk of hyperkalemia, and therefore, their co-administration should be approached with caution and close monitoring of potassium levels, as recommended by recent guidelines 1. When considering the use of ACE inhibitors and Bactrim together, it is essential to understand the mechanisms by which they can raise potassium levels. ACE inhibitors decrease aldosterone production, reducing potassium excretion in the kidneys, while trimethoprim blocks sodium channels in the distal tubule, impairing potassium secretion similar to potassium-sparing diuretics 1.

Key Considerations

• The risk of hyperkalemia is particularly high in patients with other risk factors such as diabetes, renal impairment, or advanced age.
• Baseline potassium should be checked before starting the combination, followed by monitoring within 3-5 days of initiating therapy.
• Patients should be educated about symptoms of hyperkalemia including muscle weakness, palpitations, and numbness.
• In high-risk patients, consider alternative antibiotics when possible or temporary ACE inhibitor dose reduction during the antibiotic course.

Management of Hyperkalemia

According to the latest clinical management guidelines, monitoring serum K+ should be individualized, with increased frequency of monitoring considered for patients with chronic kidney disease, diabetes, heart failure, or a history of hyperkalemia and for those receiving RAASi therapy 1.

• Recent clinical studies suggest that the newer K+ binders (patiromer sorbitex calcium and sodium zirconium cyclosilicate) may facilitate optimization of RAASi therapy.
• Enhancing the knowledge of primary care physicians and internists with respect to the safety profiles of these newer K+ binders may increase confidence in managing patients with hyperkalemia.

From the FDA Drug Label

In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of sulfamethoxazole and trimethoprim oral suspension and an angiotensin converting enzyme inhibitor. The trimethoprim component of sulfamethoxazole and trimethoprim oral suspension may cause hyperkalemia when administered to patients with underlying disorders of potassium metabolism, with renal insufficiency or when given concomitantly with drugs known to induce hyperkalemia, such as angiotensin converting enzyme inhibitors. Close monitoring of serum potassium is warranted in these patients

The concomitant use of ace inhibitors and Bactrim (sulfamethoxazole/trimethoprim) may increase the risk of hyperkalemia, particularly in elderly patients or those with underlying disorders of potassium metabolism or renal insufficiency.

• Key points:
  • Close monitoring of serum potassium is recommended
  • Discontinuation of sulfamethoxazole and trimethoprim oral suspension treatment may be necessary to help lower potassium serum levels
  • The risk of hyperkalemia is increased when Bactrim is given concomitantly with drugs known to induce hyperkalemia, such as angiotensin converting enzyme inhibitors 2 2

From the Research

ACE Inhibitors and Hyperkalemia

• ACE inhibitors can increase serum potassium levels, especially when combined with potassium-sparing diuretics, leading to hyperkalemia, particularly in patients with renal insufficiency 3.
• The use of ACE inhibitors can lead to hyperkalemia due to the blockade of the angiotensin-converting enzyme, which can be mitigated by attention to the clinical condition and concomitant therapy 4.

Bactrim (Trimethoprim-Sulfamethoxazole) and Hyperkalemia

• Trimethoprim-sulfamethoxazole can cause hyperkalemia, especially in patients receiving inhibitors of the renin-angiotensin system, such as ACE inhibitors or angiotensin receptor blockers 5.
• The mechanism of trimethoprim-induced hyperkalemia is through the competitive inhibition of epithelial sodium channels in the distal nephron, similar to the potassium-sparing diuretic amiloride 6.
• The risk of hyperkalemia with trimethoprim treatment is increased in patients with higher dosages and underlying renal impairment, as well as those with disturbances in potassium homeostasis, such as hypoaldosteronism 6.

Combination of ACE Inhibitors and Bactrim

• The combination of ACE inhibitors and trimethoprim-sulfamethoxazole can increase the risk of hyperkalemia-associated hospitalization, especially in elderly patients with renal insufficiency or those receiving other medications that impair renal potassium excretion 5.
• The use of alternate antibiotic therapy should be considered in patients treated with ACE inhibitors or angiotensin receptor blockers when clinically appropriate to minimize the risk of hyperkalemia 5.