Drugs That Cause Hyperkalemia
Numerous medications can cause hyperkalemia by decreasing potassium excretion or increasing potassium intake, with renin-angiotensin-aldosterone system inhibitors and potassium-sparing diuretics being the most common culprits. 1
Medications That Decrease Potassium Excretion
Renin-Angiotensin-Aldosterone System Inhibitors
- ACE inhibitors (e.g., lisinopril, enalapril) 1
- Angiotensin receptor blockers (ARBs) (e.g., losartan, valsartan) 1, 2
- Mineralocorticoid receptor antagonists (MRAs) (e.g., spironolactone, eplerenone) 1, 3
- Direct renin inhibitors (e.g., aliskiren) 1
- Sacubitril/valsartan 1
Potassium-Sparing Diuretics
- Spironolactone - can cause severe hyperkalemia, especially when combined with ACE inhibitors 3, 4
- Triamterene 1
- Amiloride 1
Other Medications
- Beta-blockers (e.g., metoprolol, propranolol) 1, 5
- NSAIDs (e.g., ibuprofen, naproxen) 1, 6
- Calcineurin inhibitors (e.g., cyclosporine, tacrolimus) 1
- Heparin and low molecular weight heparin 1, 3
- Trimethoprim-sulfamethoxazole 1
- Pentamidine 1, 5
- Digitalis 1
- Mannitol 1
- Penicillin G (in high doses) 1
Medications That Increase Potassium Intake/Administration
- Potassium supplements 1
- Salt substitutes (e.g., those used in DASH diet) 1
- Stored blood products 1
- Herbal supplements including:
- Alfalfa, dandelion, dried toad skin, hawthorne berry, horsetail, lily of the valley, milkweed, nettle, noni juice, Siberian ginseng 1
- Amino acids (aminocaproic acid, arginine, lysine) 1
Risk Factors for Drug-Induced Hyperkalemia
Certain patient factors significantly increase the risk of developing hyperkalemia when taking these medications:
- Renal impairment (creatinine >1.5 mg/dL) 7, 4
- Diabetes mellitus 8, 4
- Advanced age (>70 years) 7, 4
- Heart failure 7, 1
- Volume depletion or dehydration 4, 8
- Concurrent use of multiple medications that can cause hyperkalemia 4, 5
Monitoring Recommendations
- Monitor serum potassium within 1 week of initiation or titration of medications known to cause hyperkalemia 3, 2
- More frequent monitoring is needed when combining drugs that cause hyperkalemia or in patients with impaired renal function 3, 4
- Regular monitoring of renal function is essential when using these medications 2, 6
- Consider reducing doses or discontinuing medications if hyperkalemia develops 3, 2
Dangerous Drug Combinations
Certain drug combinations pose particularly high risks for hyperkalemia:
- ACE inhibitors + spironolactone (especially at doses >25 mg daily) 4, 6
- Multiple RAAS inhibitors used concurrently 1, 5
- RAAS inhibitors + potassium-sparing diuretics 3, 6
- RAAS inhibitors + trimethoprim-sulfamethoxazole 1, 5
- RAAS inhibitors + NSAIDs, especially in patients with renal impairment 6, 5
Prevention Strategies
- Use the lowest effective dose of medications known to cause hyperkalemia 4, 3
- Consider using loop or thiazide diuretics concurrently with RAAS inhibitors to reduce hyperkalemia risk 7, 1
- Avoid potassium supplements and salt substitutes in patients taking medications that can cause hyperkalemia 3
- Educate patients about dietary sources of potassium that should be limited 1
- Review all medications regularly to identify potential interactions 9, 5