Ibuprofen × Spironolactone

Ibuprofen blocks prostaglandin synthesis in the kidney, which weakens the diuretic, natriuretic and blood-pressure-lowering effect of spironolactone (spironolactone labels). Spironolactone blocks aldosterone, so the kidneys keep potassium; nonsteroidal anti-inflammatory drugs (NSAIDs) given with potassium-sparing diuretics raise the risk of hyperkalaemia (both SmPCs). NSAIDs reduce renal blood flow, and taken with a diuretic they raise the risk of kidney damage, especially in older or dehydrated patients and in those with heart, kidney or liver disease (ibuprofen SmPC).

Hyperkalaemia often causes no symptoms and shows only in blood tests. At higher potassium levels, the patient may have tingling and numbness, muscle weakness and cramps, flaccid paralysis and heart rhythm disturbances (spironolactone SmPC). Worsening kidney function shows as rising creatinine and urea and reduced urine output. If the diuretic effect weakens, oedema increases and weight and blood pressure go up.

Use the combination with caution and check serum potassium while the patient takes both drugs (ibuprofen SmPC). Check potassium within 1 week of starting or increasing spironolactone and regularly after that (spironolactone label, US Food and Drug Administration, FDA). With nonsteroidal anti-inflammatory drugs, more frequent checks may be needed (spironolactone FDA label). Keep the patient well hydrated and check renal function, volume status and the diuretic effect of spironolactone after starting the combination and periodically (ibuprofen SmPC, spironolactone labels). In patients with heart, liver or kidney disease, keep the ibuprofen dose as low and the course as short as possible (ibuprofen SmPC). If hyperkalaemia occurs, reduce the spironolactone dose or stop it (spironolactone FDA label). In severe heart failure, interrupt spironolactone if potassium is above 5 mmol/L or creatinine above 4 mg/dL (spironolactone SmPC). Ibuprofen is contraindicated when the glomerular filtration rate is below 30 mL/min and in New York Heart Association class IV heart failure, and spironolactone in hyperkalaemia or acute renal failure (both SmPCs).