From the Guidelines
Medications that can cause hyperkalemia include ACE inhibitors, ARBs, potassium-sparing diuretics, NSAIDs, trimethoprim, heparin, beta-blockers, calcineurin inhibitors, and potassium supplements, which can increase the risk of hyperkalemia through various mechanisms, as reported in the most recent study 1. These medications can cause hyperkalemia by:
- Decreasing aldosterone production, reducing potassium excretion (ACE inhibitors and ARBs)
- Directly blocking renal potassium secretion (potassium-sparing diuretics)
- Decreasing renal blood flow and glomerular filtration (NSAIDs)
- Blocking potassium channels in the collecting duct (trimethoprim)
- Suppressing aldosterone production (heparin)
- Impairing cellular potassium uptake (beta-blockers)
- Reducing potassium excretion (calcineurin inhibitors) Patients with kidney disease, diabetes, heart failure, or those taking multiple potassium-raising drugs are at highest risk, as noted in 1 and 1. Regular potassium monitoring is essential when starting these medications, particularly in high-risk patients, with levels checked within 1-2 weeks of initiation and after dose increases, as recommended in 1. Some specific medications that can cause hyperkalemia include:
- ACE inhibitors (like lisinopril, enalapril)
- ARBs (losartan, valsartan)
- Potassium-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene)
- NSAIDs (ibuprofen, naproxen)
- Trimethoprim (in Bactrim)
- Heparin
- Beta-blockers (especially non-selective ones like propranolol)
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Potassium supplements It is also important to note that certain patient populations have an increased risk of hyperkalemia-associated morbidity and mortality, including patients with advanced stages of CKD, HF, resistant hypertension, diabetes, myocardial infarction (MI), and/or combinations of these conditions, as reported in 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 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 ... hyperkalemia
Medications that can cause hyperkalemia include:
- Spironolactone
- Angiotensin converting enzyme inhibitors
- Angiotensin receptor blockers, such as losartan
- Potassium supplementation
- Potassium-containing salt substitutes
- Aliskiren (especially when used in combination with other RAS inhibitors) The risk of hyperkalemia is increased when these medications are used in combination or in patients with impaired renal function 2 3
From the Research
Medications Causing Hyperkalemia
Medications that can cause hyperkalemia include:
- Amino acids
- Beta-blockers
- Calcium channel blockers
- Suxamethonium
- Mannitol
- 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 4
Specific Medication Combinations
Certain medication combinations can increase the risk of hyperkalemia, such as:
- Combining potassium-sparing medications, which can result in profound hyperkalemia 5
- Using trimethoprim-sulfamethoxazole with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), which can increase the risk of hyperkalemia-associated hospitalization 6
Patient Risk Factors
Patient risk factors for hyperkalemia include:
- Age ≥ 75 years
- Diabetes
- Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2)
- Systolic blood pressure < median of 123 mm Hg 7
- Chronic kidney disease (CKD) stage 3-4 8
Medication Safety and Efficacy
The safety and efficacy of certain medications, such as eplerenone and spironolactone, have been studied in patients at high risk for hyperkalemia or worsening renal function:
- Eplerenone was found to be both efficacious and safe in patients with chronic heart failure and reduced ejection fraction, even in those at high risk of developing hyperkalemia or worsening renal function 7
- Spironolactone was found to retard CKD progression to end-stage renal disease, but increased the risk of hyperkalemia-associated hospitalization 8