Spironolactone Contraindications
Spironolactone is absolutely contraindicated in patients with hyperkalemia, Addison's disease, and those taking eplerenone concurrently. 1
Absolute Contraindications
- Hyperkalemia (potassium >5.0 mEq/L at baseline) 1, 2
- Addison's disease 1
- Concomitant use of eplerenone 1
Critical Renal Function Thresholds
Do not initiate spironolactone when:
- Serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women 2
- Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² 2
The risk of life-threatening hyperkalemia increases progressively when serum creatinine exceeds 1.6 mg/dL, making careful patient selection essential 2.
High-Risk Populations Requiring Extreme Caution
Avoid or use with intensive monitoring in:
- Elderly patients - particularly those with low muscle mass where creatinine may not accurately reflect true renal function 2
- Diabetic patients - significantly increased risk of hyperkalemia 2, 3
- Patients with liver disorders 2
- Patients with kidney disorders beyond the absolute contraindication thresholds 2
Dangerous Drug Combinations (Relative Contraindications)
Spironolactone should not be combined with:
- Potassium supplements - dramatically increases hyperkalemia risk 2
- Other potassium-sparing diuretics - additive hyperkalemia risk 2
- Potent CYP3A4 inhibitors - increases spironolactone levels 2
- Combined ACE inhibitor + ARB therapy - the triple combination of ACE inhibitor, ARB, and aldosterone antagonist should be avoided due to excessive hyperkalemia risk 2
- NSAIDs and COX-2 inhibitors - can precipitate worsening renal function and hyperkalemia 2
- High-dose ACE inhibitors (captopril ≥75 mg daily; enalapril or lisinopril ≥10 mg daily) - increases hyperkalemia risk 2
Clinical Context: Real-World Hyperkalemia Risk
Population-based data from Ontario demonstrated that after widespread adoption of spironolactone, hospitalizations for hyperkalemia increased from 2.4 to 11 per thousand patients, with associated mortality rising from 0.3 to 2 per thousand 2. This stark contrast to the 2% incidence in controlled trials underscores that clinical trial populations are highly selected and real-world toxicity is substantially higher 2.
In one series, hyperkalemia occurred in 24% of patients receiving spironolactone in routine practice, with half having potassium levels exceeding 6 mEq/L 2. Life-threatening hyperkalemia requiring hemodialysis occurred in 68% of affected patients, with a mean hospitalization of 12 days 3.
Specific Clinical Scenarios Requiring Avoidance
Do not use spironolactone in patients with:
- Risk for dehydration - conditions causing volume depletion (gastroenteritis, diarrhea) can precipitate acute hyperkalemia even in previously stable patients 2, 3
- Worsening heart failure - acute decompensation increases hyperkalemia risk 3
- Pregnancy - teratogenic effects make this an absolute contraindication 4
Special Consideration: Men and Hormonal Effects
While not an absolute contraindication, men should be counseled about feminization risks including gynecomastia (10% incidence), breast discomfort, and decreased libido 2, 4. Eplerenone is preferred in men who develop these symptoms 2.
End-Stage Renal Disease Exception
Patients on hemodialysis may represent a unique exception - small pilot studies suggest spironolactone may be safer in ESRD patients on regular hemodialysis than in those with moderate-severe CKD not on dialysis, though this remains investigational and requires larger confirmatory studies 5, 6.