From the Guidelines
Drugs that can cause hyperkalemia include potassium-sparing diuretics, beta-blockers, NSAIDs, sacubitril/valsartan, renin-angiotensin-aldosterone inhibitors, and direct renin inhibitors, among others. According to a recent expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors 1, several medications can lead to hyperkalemia by decreasing potassium excretion or increasing potassium intake/administration.
Mechanisms of Hyperkalemia
The mechanisms by which these medications cause hyperkalemia include:
- Decreased potassium excretion:
- Potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride)
- Beta-blockers
- NSAIDs
- Sacubitril/valsartan
- Renin-angiotensin-aldosterone inhibitors (RAASi): ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists (MRAs)
- Direct renin inhibitors (aliskiren)
- Increased potassium intake/administration:
- Potassium supplements
- Salt substitute (e.g., DASH)
- Certain fruits and herbs
Clinical Implications
It is essential to monitor potassium levels regularly in patients taking these medications, especially those with kidney disease or other risk factors for hyperkalemia 1. If hyperkalemia develops, the medication may need to be adjusted or discontinued under medical supervision to prevent life-threatening complications. The treatment of hyperkalemia often involves a combination of calcium carbonate, hyperosmolar sodium, insulin, and beta adrenoceptor agonists, as well as potassium-lowering agents such as loop diuretics and potassium binders 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)]. The trimethoprim component of sulfamethoxazole and trimethoprim 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.
The following drugs can cause hyperkalemia:
- Spironolactone
- Trimethoprim-sulfamethoxazole
- Angiotensin converting enzyme inhibitors
- Angiotensin receptor blockers These drugs may increase the risk of hyperkalemia, especially in patients with impaired renal function or those taking concomitant potassium supplementation 2 3.
From the Research
Drugs that Cause Hyperkalemia
The following drugs can cause hyperkalemia:
- Potassium supplements
- Potassium-sparing diuretics
- Renin-angiotensin-aldosterone-system (RAAS) inhibitors
- Angiotensin-converting enzyme inhibitors
- Angiotensin-II receptor blockers
- Direct renin inhibitors
- Nonsteroidal anti-inflammatory drugs
- Calcineurin inhibitors
- Heparin and derivatives
- Aldosterone antagonists
- Trimethoprim
- Pentamidine
- Potassium-containing agents
- Sulfamethoxazole-trimethoprim (Co-trimoxazole)
- Beta-blockers
- Calcium channel blockers
- Suxamethonium
- Mannitol
- Amino acids
Mechanisms of Hyperkalemia
Drugs can cause hyperkalemia by:
- Promoting transcellular potassium shift
- Impairing renal potassium excretion
- Increasing potassium supply
- Inhibiting the renin-angiotensin-aldosterone system
Risk Factors for Hyperkalemia
The following are risk factors for hyperkalemia:
- Decreased renal function (eGFR <50 ml/min) 4
- Use of multiple potassium-influencing drugs concurrently 4, 5
- Advanced age 4
- Diabetes mellitus 4
- Congestive heart failure 4
- Use of heparin, digoxin, non-steroidal anti-inflammatory drugs, beta-blockers, calcineurin antagonists, and trimethoprim 4
Specific Drug Combinations that Increase the Risk of Hyperkalemia
The following drug combinations can increase the risk of hyperkalemia: