What medications can cause hyperkalemia (elevated potassium levels)?

From the Guidelines

Medications that can cause hyperkalemia include ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, certain antibiotics, heparin, and immunosuppressants, which can increase potassium levels by blocking its excretion, shifting it from cells to the bloodstream, or directly adding potassium to the body. These medications are commonly used to treat high blood pressure, heart failure, and other conditions, but can have serious consequences if potassium levels become too high. According to the most recent study 1, treatment with ACE inhibitors and ARBs or MRAs can cause AKI and hyperkalemia, while diuretics can cause AKI and either hypokalemia or hyperkalemia. Some key medications that can cause hyperkalemia include:

• ACE inhibitors (like lisinopril, enalapril, and ramipril)
• ARBs (such as losartan, valsartan, and candesartan)
• Potassium-sparing diuretics (including spironolactone, eplerenone, and triamterene)
• NSAIDs (like ibuprofen and naproxen)
• Certain antibiotics (trimethoprim-sulfamethoxazole)
• Heparin (blood thinner)
• Immunosuppressants (cyclosporine, tacrolimus)
• Potassium supplements and salt substitutes containing potassium chloride It is essential to monitor potassium levels regularly, especially in patients with kidney disease, diabetes, or heart failure, as these conditions already predispose to potassium abnormalities 1.

From the FDA Drug Label

Spironolactone can cause hyperkalemia. This risk is increased by impaired renal function or concomitant potassium supplementation, potassium-containing salt substitutes or drugs that increase potassium, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers [see Drug Interactions (7. 1)] 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 Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy

The medications that can cause hyperkalemia (elevated potassium levels) include:

• Spironolactone
• ACE inhibitors
• Angiotensin II antagonists (such as losartan)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Heparin and low molecular weight heparin
• Aliskiren
• Potassium supplementation
• Salt substitutes containing potassium
• Drugs that increase potassium 2, 2, 3

From the Research

Medications that Can Cause Hyperkalemia

The following medications can cause hyperkalemia by interfering with potassium homeostasis:

• Medications that alter transmembrane potassium movement:
  • Amino acids
  • Beta-blockers
  • Calcium channel blockers
  • Suxamethonium
  • Mannitol 4
• Medications that impair renal potassium excretion:
  • 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 4
• Potassium-containing agents 4

Specific Medication Combinations and Hyperkalemia Risk

Certain medication combinations can increase the risk of hyperkalemia:

• Combined use of ACE-inhibitors and potassium-sparing agents, such as spironolactone, can increase the risk of severe hyperkalemia 5
• The combination of an ACE-inhibitor and spironolactone is indicated in patients with cardiac insufficiency NYHA-class II-IV and an ejection fraction of ≤ 35%, but close monitoring of serum potassium and renal function is mandatory 5

Prevalence of Hyperkalemia with Antihypertensive Medications

The prevalence of hyperkalemia has been evaluated in patients taking antihypertensive medications:

• Angiotensin-converting enzyme inhibitors were the antihypertensive medication class most strongly associated with hyperkalemia 6
• Hyperkalemia is common, and future research may enable optimal renin-angiotensin-aldosterone system inhibitor use with improved management of hyperkalemia 6

Safety of Combining ACE Inhibitors and Potassium-Sparing Diuretics

The safety of combining ACE inhibitors and potassium-sparing diuretics has been assessed:

• A retrospective study found that combining an ACE inhibitor with a potassium-sparing diuretic did not result in clinically relevant hyperkalemia, as long as renal function was normal and serum potassium concentration was monitored closely 7