naproxen and lisinopril

NSAIDs inhibit renal prostaglandin synthesis, reducing afferent arteriolar vasodilation and renal blood flow. ACE inhibitors such as lisinopril dilate the efferent arteriole. In volume-depleted or renin-dependent states, this combination can cause a precipitous fall in glomerular filtration. In addition, both drugs can increase serum potassium via different mechanisms, and NSAIDs cause sodium retention that blunts the antihypertensive effect of lisinopril.

In clinical practice, this interaction may increase blood pressure to hypertensive levels and reduce the efficacy of lisinopril. More seriously, it can precipitate acute kidney injury, particularly in elderly patients, those with baseline renal impairment, heart failure, or concurrent diuretic use. Hyperkalaemia may develop, which can be life-threatening in severe cases. Symptoms may include fatigue, palpitations, and neuro-muscular abnormalities, but often are subtle until advanced.

Prescribers should avoid this combination if possible, especially in high-risk patients. If co-administration is necessary, use the lowest effective NSAID dose for the shortest duration, and consider substitution with paracetamol or another non-NSAID analgesic. Monitor serum creatinine, estimated GFR, blood pressure, and serum potassium at baseline, within one week of starting the combination, and thereafter as clinically indicated. Advise patients to maintain adequate hydration and report symptoms such as oedema, reduced urine output, or weakness.

This interaction is well recognised and documented in national formularies and clinical guidelines. Multiple observational studies and meta-analyses confirm an increased risk of acute kidney injury, hyperkalaemia, and blood pressure elevation with combined NSAID and ACE inhibitor use. However, causality in individual cases varies; further randomised controlled trials specifically examining this interaction are limited.