Spironolactone Colestyramine

Colestyramine in combination with spironolactone has been reported to cause severe hyperkalemia (25), presumably because it causes exchange of chloride for... 

A few case reports have described hyperchloraemic metabolic acidosis, which was associated with the use of colestyramine and spironolactone. 

Four case reports describe the development of hyperchloraemic metabolic acidosis in patients with liver cirrhosis taking colestyramine (up to about 25 g daily), who were also taking spironolactone 75 mg or 100 mg daily. " One patient developed significant hyperkalaemia (potassium 8 mmol/L), and 2 patients developed mild renal impairment. One patient had recently recovered from a respiratory tract infection, which the authors suggested may have contributed to the acidosis. Acidosis resolved when the colestyramine was stopped. 

Bicarbonate has been shown to compete in vitro with bile acids for binding sites on the colestyramine resin. The chloride ions in the colestyramine resin may cause an anion exchange of not only the bile salts, as is the intention, but also bicarbonate in the small bowel. This removal of bicarbonate from the body can predispose to the development of a hyperchloraemic metabolic acidosis and hyperkalaemia. This might be exacerbated by the bicarbonate-losing and hyperkalaemic effects of spironolactone. 

In healthy subjects with normal renal function, acidosis does not usually occur, as the kidneys correct it by increasing the excretion of chloride and production of bicarbonate. " However, in patients with renal impairment, volume depletion (e.g. secondary to diuretics) or concurrent conditions that predispose to acidosis, this interaction may be significant. It has been suggested that electrolytes should be closely monitored when patients who are at risk of an interaction are taking colestyramine and spironolactone, although note that the interaction appears to be rare. 

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