Can Aldactone (spironolactone) cause hyperkalemia?

Hyperkalemia Risk with Aldactone (Spironolactone)

Yes, Aldactone (spironolactone) can cause hyperkalemia, which is its major risk and potentially life-threatening side effect due to its mechanism of inhibiting potassium excretion. 1, 2

Mechanism and Risk

Spironolactone is a potassium-sparing diuretic that functions as an aldosterone antagonist, binding to the distal tubule in the kidney as a competitive inhibitor of aldosterone. This mechanism:

• Slows the exchange of sodium and potassium in the distal tubule
• Inhibits potassium excretion, leading to potassium retention
• Can aggravate renal dysfunction, further impairing potassium excretion 1

Incidence of Hyperkalemia

The incidence of hyperkalemia with spironolactone varies significantly:

• 2% in controlled clinical trials 1
• Up to 24% in real-world clinical practice 1
• As high as 50.4% in patients with chronic kidney disease after 4 weeks of treatment 3

In one population-based analysis in Ontario, Canada, after increased spironolactone prescriptions:

• Hospitalizations for hyperkalemia increased from 2.4 to 11 patients per thousand
• Associated mortality increased from 0.3 to 2 per thousand 1

Risk Factors for Hyperkalemia

The following factors increase the risk of developing hyperkalemia with spironolactone:

1. Impaired renal function: Risk increases progressively when serum creatinine exceeds 1.6 mg/dL 1
2. Baseline serum potassium >5.0 mEq/L 1
3. Concomitant medications:
   • Higher doses of ACE inhibitors (captopril ≥75 mg daily; enalapril or lisinopril ≥10 mg daily) 1
   • ARBs (angiotensin receptor blockers) 2
   • NSAIDs and COX-2 inhibitors 1
   • Potassium supplements 1, 2
   • Other potassium-sparing diuretics 2
4. Medical conditions:
   • Diabetes mellitus 2, 4, 5
   • Older age 4, 5
   • Worsening heart failure 4
   • Dehydration or volume depletion 1, 4

Monitoring Recommendations

To minimize the risk of hyperkalemia:

1. Before starting spironolactone:

   • Check baseline serum potassium and renal function
   • Do not start if potassium >5.0 mEq/L or severe renal impairment

2. After initiation:

   • Check potassium and renal function within 3 days
   • Recheck at 1 week after initiation
   • Monitor monthly for the first 3 months
   • Continue monitoring every 3 months thereafter 1

3. Additional monitoring cycles should be initiated when:

   • ACE inhibitors or ARBs are added or increased in dose
   • Dehydration occurs (e.g., diarrhea, gastroenteritis)
   • Other conditions that may affect potassium levels develop 1

Dosing Considerations

• Start with lower doses: 12.5 mg daily or on alternate days 1
• For patients with reduced renal function (eGFR 30-50 mL/min), start with 12.5 mg daily 1
• Avoid use when eGFR <30 mL/min 1
• Do not exceed 25 mg daily in high-risk patients 4

Management of Hyperkalemia

If hyperkalemia develops (potassium >5.5 mEq/L):

• Discontinue or reduce the dose of spironolactone
• Stop any potassium supplements
• Evaluate the entire medication regimen
• Treat the hyperkalemia according to its severity

Common Pitfalls to Avoid

1. Triple therapy combination: Routine combination of ACE inhibitors, ARBs, and aldosterone antagonists should be avoided due to high hyperkalemia risk 1

2. Inadequate monitoring: Failure to check potassium levels as recommended is a common cause of preventable hyperkalemia

3. Failure to adjust for real-world factors: Clinical trial populations are highly selected; real-world patients often have more comorbidities and higher risk of toxicity 1

4. Overlooking volume depletion: Dehydration significantly increases hyperkalemia risk and should be addressed urgently 1

5. Ignoring drug interactions: Adding NSAIDs or other medications that affect potassium without appropriate monitoring 1, 2