Ramipril

Metabolism

Hypoglycemia has been attributed to several drugs in a complicated sequence of effects [ ].

• A 64-year-old man with type II diabetes, hypertension, and bilateral renal artery stenosis presented with confusion and dysarthria related to profound hypoglycemia (2.2 mmol/l). He was taking naproxen 500 mg bd, ramipril 2.5 mg/day, glibenclamide 2.5 mg bd, metformin 850 mg bd, a thiazide diuretic, terazosin, ranitidine, paracetamol, and codeine. His plasma creatinine concentration, previously 185 μmol/l, was 362 μmol/l and it fell to 210 μmol/l after the withdrawal of ramipril and naproxen.

The authors discussed the possible role of renal insufficiency, resulting from co-prescription of naproxen and ramipril in the presence of volume depletion, which may have increased the risk of hypoglycemia related to glibenclamide plus metformin.

Electrolyte balance

Hyperkalemia is a concern when ACE inhibitors are co-administered with potassium-sparing diuretics, such as triamterene or amiloride, or aldosterone antagonists, such as spironolactone. Both classes of agents are increasingly being used, in both heart failure and hypertension. A 59-year-old patient with both of these diagnoses was given ramipril 5 mg/day, hydrochlorothiazide 12.5 mg/day, and spironolactone 25 mg/day and developed acute renal impairment and severe hyperkalemia (9.3 mmol/l) [ ].

Hematologic

Neutropenia and agranulocytosis have both rarely been attributed to ACE inhibitors.

• Ramipril-induced agranulocytosis has been reported in a 55-year-old man with hypertensive chronic renal insufficiency [ ]. He was also taking metoprolol, clonidine, furosemide, simvastatin, aspirin, and amlodipine, but was given ramipril 4 days before developing weakness and a neutropenic fever. A bone marrow biopsy showed moderate hypocellularity. An in vitro lymphocyte cytotoxicity assay was performed with furosemide and ramipril; there was a cytotoxic response to ramipril.