What medications can cause hyperkalemia?

Medications That Cause Hyperkalemia

Medications that most commonly cause hyperkalemia include potassium-sparing diuretics, ACE inhibitors, ARBs, direct renin inhibitors, and beta-blockers, which should be used with caution in patients with renal impairment or when used in combination. 1

Primary Medications That Cause Hyperkalemia

1. Medications That Decrease Potassium Excretion

• Potassium-sparing diuretics

  • Spironolactone (25-100 mg daily) 1, 2
  • Eplerenone (50-100 mg daily) 1
  • Triamterene 1
  • Amiloride 1

• Renin-Angiotensin-Aldosterone System Inhibitors

  • ACE inhibitors (e.g., lisinopril) 3
  • Angiotensin receptor blockers (ARBs) 1
  • Direct renin inhibitors (e.g., aliskiren) 1
  • Sacubitril/valsartan 1

• Other medications that impair renal potassium excretion

  • NSAIDs 1, 4
  • Beta-blockers 1, 4
  • Trimethoprim-sulfamethoxazole 1
  • Calcineurin inhibitors (cyclosporine, tacrolimus) 1, 4
  • Heparin and low molecular weight heparin 1, 4
  • Pentamidine 1
  • Digitalis 1
  • Mannitol 1
  • Penicillin G (high doses) 1

2. Medications That Increase Potassium Supply

• Potassium supplements 1
• Salt substitutes containing potassium 1
• Stored blood products 1

Risk Factors for Medication-Induced Hyperkalemia

1. Renal impairment (especially GFR <45 mL/min) 1, 5
2. Diabetes mellitus 5
3. Advanced age (particularly >70 years) 5
4. Combination therapy (especially ACE inhibitors with potassium-sparing diuretics) 5, 6
5. Volume depletion or dehydration 5
6. Heart failure 5

High-Risk Medication Combinations

The most dangerous combinations that can lead to severe hyperkalemia include:

1. ACE inhibitors + potassium-sparing diuretics 3, 5

   • This combination can cause life-threatening hyperkalemia, especially in patients with renal impairment
   • In one study, patients developed severe hyperkalemia (mean 7.7 mmol/L) requiring hospitalization 5

2. Dual RAAS blockade 7

   • Combining ACE inhibitors, ARBs, and/or direct renin inhibitors significantly increases hyperkalemia risk
   • Avoid using aliskiren with ACE inhibitors or ARBs, especially in patients with diabetes or renal impairment 1

3. Triple therapy with NSAID + ACE inhibitor/ARB + diuretic 8, 4

   • This combination can cause both hyperkalemia and acute kidney injury

Monitoring Recommendations

For patients on medications that can cause hyperkalemia:

• Check serum potassium and renal function:

  • Within 1 week of starting spironolactone or other potassium-sparing diuretics 2
  • 1-4 weeks after starting ACE inhibitors or ARBs 3
  • More frequently in high-risk patients (elderly, diabetics, renal impairment) 2

• For patients on spironolactone:

  • Monitor potassium at 1,4,8, and 12 weeks after initiation and after any dose increase 1
  • Then monitor every 6 months for maintenance therapy 1

Management of Medication-Induced Hyperkalemia

• Mild hyperkalemia (K+ 5.0-5.5 mmol/L):

  • Consider dose reduction of offending medication
  • More frequent monitoring

• Moderate hyperkalemia (K+ 5.6-6.0 mmol/L):

  • Reduce dose or discontinue medication
  • Consider alternative medications
  • For spironolactone: halve the dose and monitor closely 1

• Severe hyperkalemia (K+ >6.0 mmol/L):

  • Immediately discontinue offending medication 1, 2
  • Urgent medical treatment for hyperkalemia
  • Consider hemodialysis in severe cases 5

Practical Considerations

• When using ACE inhibitors with spironolactone in heart failure:

  • Limit spironolactone dose to 25 mg daily 5, 6
  • Avoid in patients with GFR <30 mL/min 5
  • Avoid additional potassium supplements 2

• For patients requiring RAAS inhibitors who develop hyperkalemia:

  • Consider newer potassium binders to maintain RAAS inhibitor therapy
  • Adjust doses of medications rather than discontinuing beneficial therapies

• Beta-blockers can cause hyperkalemia through inhibition of Na+/K+-ATPase, especially non-selective agents like propranolol 4

Remember that medication-induced hyperkalemia can be asymptomatic but potentially life-threatening, with risk of cardiac arrhythmias and sudden death. Careful medication selection, appropriate dosing, and regular monitoring are essential for prevention.