ramipril and spironolactone

Additive pharmacodynamic effect: ramipril inhibits angiotensin-converting enzyme, reducing aldosterone secretion, while spironolactone blocks aldosterone receptors in the distal nephron. Both actions decrease renal potassium excretion, leading to an additive rise in serum potassium. Concurrent use also increases risk of acute kidney injury, further impairing potassium handling.

Clinically, co-prescription increases the risk of hyperkalaemia, which can be life-threatening through cardiac arrhythmias. The risk is amplified in patients with pre-existing renal impairment, diabetes, heart failure, or those receiving other potassium-sparing agents or potassium supplements. This combination is commonly used in heart failure for mortality benefit, but requires careful monitoring.

Prescribers may use this combination in selected patients (e.g., heart failure) with close monitoring. Measure serum potassium and creatinine before starting, then within 1 week, and regularly thereafter, especially after dose changes. Avoid in patients with significant renal impairment, baseline hyperkalaemia, or high risk of worsening renal function. Consider alternatives such as eplerenone or loop diuretics if risk is high.

Association is well documented in clinical trials and guidelines for heart failure (e.g., RALES, EMPHASIS-HF). Risk of hyperkalaemia is acknowledged in product monographs. No specific citations needed.