Contraindications to Eplerenone and Losartan Combination
The combination of eplerenone and losartan is not absolutely contraindicated, but requires careful patient selection and monitoring due to the significant risk of hyperkalemia when combining an aldosterone antagonist with an ARB. 1, 2
Absolute Contraindications to Eplerenone
When considering eplerenone in any patient (including those on losartan), the following are absolute contraindications per FDA labeling 1:
- Serum potassium >5.5 mEq/L at initiation 1
- Creatinine clearance ≤30 mL/min 1
- Concomitant strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, nelfinavir) 1
Additional Contraindications for Hypertension Treatment
If using eplerenone specifically for hypertension (rather than heart failure), additional contraindications apply 1:
- Type 2 diabetes with microalbuminuria 1
- Serum creatinine >2.0 mg/dL in males or >1.8 mg/dL in females 1
- Creatinine clearance <50 mL/min 1
- Concomitant potassium supplements or other potassium-sparing diuretics 1
Absolute Contraindications to Losartan
Losartan has minimal absolute contraindications 2:
Critical Monitoring Requirements When Combining
The triple combination of ACE inhibitor, ARB, and mineralocorticoid receptor antagonist is NOT recommended due to excessive hyperkalemia risk 3. However, when combining eplerenone with losartan (without an ACE inhibitor), the following monitoring is mandatory 4:
- Check potassium and creatinine before initiation 4
- Recheck at 1 and 4 weeks after starting 4, 5
- Continue monitoring at 1,2,3, and 6 months, then every 6 months 4, 5
- If potassium rises to >5.5 mEq/L: halve the eplerenone dose 4, 5
- If potassium rises to ≥6.0 mEq/L: stop eplerenone immediately 4, 5
High-Risk Populations Requiring Extra Caution
The following patients are at increased risk for hyperkalemia when combining these agents 4, 5:
- Chronic kidney disease (especially eGFR <50 mL/min) 4, 5
- Diabetes mellitus 4, 5
- Elderly patients 5
- Those taking eplerenone doses >25 mg daily 5
Common Pitfalls to Avoid
- Do not use potassium supplements or salt substitutes high in potassium 5, 3
- Avoid NSAIDs as they increase hyperkalemia risk and impair renal function 4, 5
- Do not add an ACE inhibitor to this combination, as triple RAAS blockade significantly increases adverse events without improving outcomes 4, 3
- Monitor blood pressure closely as the combination may cause hypotension 5
When Combination is Appropriate
This combination is most appropriate in heart failure patients with 4:
- LVEF ≤40% 4
- NYHA class II-IV symptoms 4
- Already on beta-blocker therapy 4
- Normal baseline potassium and adequate renal function 4
The combination should be avoided in hypertension treatment alone, where safer alternatives exist 1.