When is spironolactone contraindicated (e.g., hyperkalaemia, estimated glomerular filtration rate < 30 mL/min/1.73 m², anuria, primary adrenal insufficiency, pregnancy especially first trimester, lactation, concurrent potassium‑sparing diuretics or angiotensin‑converting enzyme inhibitor/angiotensin receptor blocker therapy, severe hepatic failure with marked ascites)?

When to Avoid Spironolactone

Spironolactone is absolutely contraindicated in patients with hyperkalemia, Addison's disease, anuria, and when eGFR is <30 mL/min/1.73 m², and should be avoided when serum creatinine exceeds 2.5 mg/dL in men or 2.0 mg/dL in women, or when baseline potassium is >5.0 mEq/L. 1, 2

Absolute Contraindications

• Hyperkalemia (potassium >5.0 mEq/L at baseline) is an FDA-labeled absolute contraindication 2
• Addison's disease (primary adrenal insufficiency) is explicitly contraindicated per FDA labeling 2
• Anuria represents an absolute contraindication 1
• Concomitant use of eplerenone is contraindicated 2
• Severe renal impairment with eGFR <30 mL/min/1.73 m² makes spironolactone use potentially harmful due to life-threatening hyperkalemia risk 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 1
• Estimated creatinine clearance <30 mL/min 1, 3
• The risk of hyperkalemia increases progressively when serum creatinine exceeds 1.6 mg/dL, requiring enhanced surveillance 1

For patients with eGFR 30-50 mL/min/1.73 m², spironolactone may be used cautiously with reduced initial dosing (12.5 mg daily or every-other-day) and intensive monitoring 1, 3

High-Risk Clinical Scenarios Requiring Avoidance

Elderly patients (particularly those >74 years) face substantially higher hyperkalemia risk, with real-world studies showing 24-36% incidence compared to 2-5% in clinical trials 1, 4

Diabetes mellitus, especially insulin-requiring disease, significantly increases hyperkalemia susceptibility and warrants extreme caution 4, 5

Dehydration states from diarrhea, vomiting, or acute illness require immediate discontinuation of spironolactone 1, 4

Worsening heart failure precipitating acute renal dysfunction is a common trigger for life-threatening hyperkalemia in patients on spironolactone 4

Dangerous Drug Combinations to Avoid

Triple therapy with ACE inhibitor + ARB + aldosterone antagonist should never be used routinely due to dramatically increased hyperkalemia and renal dysfunction risk 1, 6

Concomitant medications requiring avoidance or extreme caution:

• NSAIDs and COX-2 inhibitors should be avoided entirely 1, 6
• Potassium supplements must be discontinued before initiating spironolactone 1, 6
• High-dose ACE inhibitors (captopril ≥75 mg daily; enalapril or lisinopril ≥10 mg daily) increase hyperkalemia risk 1
• Potassium-containing salt substitutes are contraindicated 6

Pregnancy and Lactation

Spironolactone is pregnancy category C, with animal studies demonstrating feminization of male fetuses early in gestation, making it inappropriate during pregnancy, especially the first trimester 1

Lactation represents a relative contraindication requiring careful risk-benefit assessment 1

Severe Hepatic Failure

Marked ascites with severe hepatic failure warrants avoidance due to unpredictable fluid and electrolyte shifts, though specific guideline-level evidence is limited for this population.

Real-World Safety Data Highlighting Risk

Population-based studies reveal a stark contrast between clinical trial safety and real-world practice 1, 3:

• Hyperkalemia occurred in only 2% of RALES trial patients but 15-24% in community practice
• Hospitalizations for hyperkalemia increased from 2.4 to 11 per 1,000 patients after widespread spironolactone adoption
• Associated mortality rose from 0.3 to 2 per 1,000 patients
• This disparity reflects inappropriate patient selection outside strict trial eligibility criteria 7

Common Pitfalls Leading to Inappropriate Use

Starting doses that are too high (>25 mg daily) in high-risk patients dramatically increases adverse event rates 4

Inadequate baseline assessment of renal function, particularly in elderly patients with low muscle mass where serum creatinine underestimates true renal dysfunction 1

Continuing potassium supplements after spironolactone initiation, which occurred in 23% of community-based patients despite being contraindicated 7

Prescribing to patients with relative contraindications such as baseline potassium 4.5-5.0 mEq/L or creatinine 2.0-2.5 mg/dL without enhanced monitoring protocols 7

Failure to educate patients about temporarily stopping spironolactone during acute illnesses causing dehydration 1, 4