lisinopril and spironolactone

Lisinopril inhibits ACE, reducing aldosterone synthesis, while spironolactone blocks aldosterone receptors. Both actions decrease renal potassium excretion, leading to additive hyperkalaemia. Additionally, ACE inhibitors may impair renal function, further reducing potassium clearance.

Combined therapy markedly increases serum potassium, which may cause life-threatening arrhythmias, especially in patients with renal impairment, diabetes, or pre-existing hyperkalaemia.

Use together with caution. Monitor serum potassium and creatinine at baseline, within 1-2 weeks after starting or changing doses, and then periodically. Avoid in patients with significant renal impairment or baseline potassium above 5.0 mmol/L. Consider alternative antihypertensive or renin-angiotensin system blocker, or use lower doses.

Well established, supported by product labelling and clinical guidelines. The interaction is a known major warning for both drug classes.