Enalapril × Spironolactone

Enalapril (an angiotensin-converting enzyme inhibitor, ACE-I) reduces aldosterone synthesis, while spironolactone directly blocks aldosterone receptors. Both retain potassium; hyperkalaemia develops in renal impairment or diabetes.

Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. The electrocardiogram shows peaked T waves and a widened QRS complex. Severe cases progress to cardiac arrest. The risk is higher with renal impairment, diabetes mellitus, dehydration and age over 70.

The combination is used deliberately and with potassium monitoring. The enalapril SmPC does not recommend combining enalapril with spironolactone because of the risk of hyperkalaemia; if the combination is indicated, use it with caution and frequent potassium checks (enalapril SmPC). Such an indication exists: the European Society of Cardiology (ESC) recommends a mineralocorticoid receptor antagonist such as spironolactone, together with an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker, for all patients with heart failure with reduced ejection fraction (ESC 2021). In heart failure, start spironolactone at 25 mg once daily if potassium is no higher than 5.0 mmol/L and creatinine no higher than 2.5 mg/dL, and do not exceed 50 mg a day (spironolactone SmPC). Check potassium and creatinine within a week of starting or increasing the dose, then monthly for the first 3 months, every 3 months until the end of the first year and every 6 months after that; stop spironolactone temporarily or permanently if potassium is above 5 mmol/L or creatinine above 4 mg/dL (spironolactone SmPC). Take particular care in impaired renal function and when potassium is 5.0 mmol/L or higher (ESC 2021). Potassium supplements are usually stopped when heart failure patients start spironolactone (US spironolactone label, FDA). Do not add an angiotensin II receptor blocker to an ACE inhibitor plus spironolactone because of the risk of renal dysfunction and hyperkalaemia (ESC 2021).