Trimethoprim-induced hyperkalaemia - Clinical data, mechanism, prevention and management

Cotrimoxazole (trimethoprim-sulfamethoxazole) is a combination antimicrobia l that is frequently used to treat a wide variety of infections. Only recen tly has hyperkalaemia been recognised as a relatively common complication o f therapy with trimethoprim. Hyperkalaemia has been demonstrated to occur w ith the administration of both high and standard dosages of trimethoprim. The recognition of this disorder of potassium homeostasis prompted the inve stigation and ultimate description of the mechanism by which trimethoprim c auses hyperkalaemia, Trimethoprim was found to reduce renal potassium excre tion through the competitive inhibition of epithelial sodium channels in th e distal nephron, in a manner identical to the potassium-sparing diuretic a miloride, Increased risk for hyperkalaemia with trimethoprim treatment appe ars to be related to both higher dosages and underlying renal impairment. I t is probable that other disturbances in potassium homeostasis, such as hyo poaldosteronism and treatment with medications that impair renal potassium excretion, are also risk factors for hyperkalaemia with trimethoprim therap y. Prevention of this adverse reaction depends upon recognition of patients at risk of developing hyperkalaemia as well as proper dosage selection of tri methoprim for the patient's prevailing glomerular filtration rate. Manageme nt of hyperkalaemia often mandates discontinuation of the drug, volume repl etion with isotonic fluids, and other therapies specific to hyperkalaemia. In circumstances where continued treatment with trimethoprim is required, i nduction of high urinary flow rates with intravenous fluids and a loop diur etic, as well as alkalinisation of the urine, have been shown to block the antikaliuretic effect of trimethoprim on distal nephron cells.