What medications are associated with hyperkalemia (elevated potassium levels)?

From the Guidelines

Medications most commonly associated with hyperkalemia include renin-angiotensin-aldosterone inhibitors, potassium-sparing diuretics, NSAIDs, beta-blockers, and certain antibiotics like trimethoprim-sulfamethoxazole, as outlined in a 2018 expert consensus document 1.

Medication Classes Associated with Hyperkalemia

The following classes of medications are known to contribute to hyperkalemia:

• Renin-angiotensin-aldosterone inhibitors (RAASi), including ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists, which are crucial in the management of cardiovascular diseases but can increase potassium levels 1.
• Potassium-sparing diuretics, such as spironolactone and triamterene, that directly reduce potassium excretion in the kidneys.
• NSAIDs, which can decrease renal blood flow and reduce renin release, leading to increased potassium levels.
• Beta-blockers, which can inhibit cellular potassium uptake.
• Certain antibiotics, notably trimethoprim-sulfamethoxazole, that can block potassium excretion channels in the renal tubules.

Management and Prevention

It's essential to monitor potassium levels regularly, especially in patients with risk factors such as renal impairment, diabetes, or heart failure, when these medications are prescribed, particularly in combination 1. The management of hyperkalemia may involve the use of loop diuretics, potassium binders, or other agents to lower potassium levels and prevent complications.

Clinical Considerations

Given the potential for hyperkalemia with these medications, clinicians should carefully weigh the benefits and risks, especially in patients with predisposing factors, and consider alternative treatments or closer monitoring of potassium levels 1. Regular assessment and adjustment of medication regimens can help mitigate the risk of hyperkalemia and its consequences on morbidity, mortality, and quality of life.

From the FDA Drug Label

Drugs and Supplements Increasing Serum Potassium: Concomitant administration of spironolactone with potassium supplementation, salt substitutes containing potassium, a diet rich in potassium, or drugs that can increase potassium, including ACE inhibitors, angiotensin II antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), heparin and low molecular weight heparin, may lead to severe hyperkalemia

• Medications associated with hyperkalemia when used with spironolactone include:
  • Potassium supplementation
  • Salt substitutes containing potassium
  • ACE inhibitors
  • Angiotensin II antagonists
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Heparin
  • Low molecular weight heparin 2

From the Research

Medications Associated with Hyperkalemia

• The following medications can cause hyperkalemia by interfering with potassium homeostasis, either by promoting transcellular potassium shift or by impairing renal potassium excretion 3:
  • Amino acids
  • Beta-blockers
  • Calcium channel blockers
  • Suxamethonium
  • Mannitol
• Medications that impair renal potassium excretion include 3:
  • Angiotensin-converting enzyme inhibitors
  • Angiotensin-II receptor blockers
  • Direct renin inhibitors
  • Nonsteroidal anti-inflammatory drugs
  • Calcineurin inhibitors
  • Heparin and derivatives
  • Aldosterone antagonists
  • Potassium-sparing diuretics
  • Trimethoprim
  • Pentamidine
• Potassium-containing agents can also cause hyperkalemia 3
• The combination of angiotensin-converting enzyme inhibitors and spironolactone can increase the risk of hyperkalemia, particularly in patients with renal insufficiency, diabetes, older age, worsening heart failure, and those at risk for dehydration 4
• Potassium-sparing diuretics, such as spironolactone, triamterene, and amiloride, can cause hyperkalemia, especially when used in combination with other medications that may increase potassium levels 5, 6

Specific Medications and Hyperkalemia Risk

• Spironolactone has been shown to have a higher antihypertensive potency than amiloride and eplerenone, but also carries a higher risk of hyperkalemia 6
• The dose equivalencies of potassium-sparing diuretics are: eplerenone-spironolactone 4.5-to-1, amiloride-spironolactone 3.3-to-1, and eplerenone-amiloride 1.4-to-1 6
• Doubling the dose of amiloride, eplerenone, and spironolactone can reduce systolic blood pressure, but also increases the risk of hyperkalemia 6