Recommended Dosing for Spironolactone and Furosemide Combination Therapy
The optimal dosing ratio is spironolactone 100 mg to furosemide 40 mg given as a single morning dose, which can be increased simultaneously every 3-5 days if response is inadequate, up to maximum doses of spironolactone 400 mg/day and furosemide 160 mg/day. 1
Clinical Context Determines Starting Dose
For Cirrhotic Ascites
- Start with spironolactone 100 mg plus furosemide 40 mg as a single morning dose 1, 2
- This 100:40 ratio maintains adequate serum potassium levels and should be preserved when escalating doses 1
- Initiate therapy in a hospital setting for cirrhotic patients and titrate slowly 3
- Combination therapy from the outset is superior to sequential monotherapy for recurrent or persistent ascites 1
For Heart Failure
- Start with lower doses: spironolactone 12.5-25 mg plus furosemide 20-40 mg daily 1, 3
- This lower starting dose is critical when combining with ACE inhibitors due to hyperkalemia risk 1, 4
- For patients with eGFR 30-50 mL/min/1.73 m², consider spironolactone 25 mg every other day 3
- Patients tolerating 25 mg daily may increase to 50 mg daily as clinically indicated 3
Dose Escalation Strategy
Increase both diuretics simultaneously every 3-5 days if weight loss remains inadequate, maintaining the 100:40 ratio to preserve potassium balance 1
- Target weight loss: maximum 0.5 kg/day without peripheral edema 1
- With peripheral edema present, faster weight loss is acceptable 2
- Maximum doses: spironolactone 400 mg/day and furosemide 160 mg/day 1, 2
Critical Monitoring Requirements
Check potassium and creatinine at 3 days, 1 week, then monthly for the first 3 months 1
High-Risk Features for Hyperkalemia:
- Baseline creatinine >1.6 mg/dL 1
- Baseline potassium >5.0 mEq/L 1
- Concomitant ACE inhibitors or ARBs 1, 5
- Diabetes mellitus 1
- Elderly patients 1
- Dehydration 1
Dose Adjustments Based on Monitoring:
- If hyperkalemia develops (>5.5 mEq/L): reduce spironolactone dose or switch to every-other-day dosing 3
- If hypokalemia develops: temporarily withhold furosemide 1
- If sodium <120-125 mmol/L: reduce or stop diuretics 1
- If creatinine rises to >2.5 mg/dL (220 μmol/L): halve the spironolactone dose 1
Absolute Contraindications
Do not give spironolactone when: 1
- Creatinine clearance <30 mL/min
- Baseline potassium >5.0 mEq/L
- Patient is taking NSAIDs or COX-2 inhibitors
Practical Administration Details
- Give as single morning dose to maximize compliance 1
- Use oral route only—intravenous diuretics can cause kidney damage from sudden fluid loss in cirrhotic patients 6
- Discontinue potassium supplements or reduce them significantly 1
- Take consistently with respect to food (with or without, but be consistent) 3
Common Pitfalls to Avoid
Avoid potassium-sparing diuretics during ACE inhibitor initiation 7—wait until ACE inhibitor dose is stable, then add spironolactone with close monitoring
Do not use loop diuretics alone as monotherapy in cirrhosis—aldosterone antagonists are the mainstay due to hyperaldosteronism 1
Monitor more frequently with ACE inhibitors—hyperkalemia risk increases even with spironolactone 25 mg/day when combined with enalapril, losartan, or candesartan 5
Avoid using ACE inhibitors other than captopril when possible—they are predictors of hyperkalemia in this combination 4