Frusemide may enhance the nephrotoxicity of cephalosporin antibiotics such as cephalothin. It can enhance the ototoxicity of aminoglycoside antibiotics. Like other diuretics, frusemide enhances the hypotensive action of antihypertensive drugs. Particular care should be taken with ACE inhibitors since combination with frusemide can result in marked reduction in blood pressure.
Cisplatin: The concomitant administration of cisplatin and frusemide carries the risk of inducing hearing defects, the 2 drugs should not be used simultaneously.
Steroids: When a glucocorticoid is administered during diuretic treatment the potassium-lowering effect of the steroid should be borne in mind.
Lithium: Concurrent use with loop diuretics may provoke lithium toxicity because of reduced renal clearance and is not recommended unless patient can be closed monitored.
Phenytoin: Phenytoin significantly reduces absorption, plasma levels and renal response of frusemide.
NSAIDS: May antagonize the natriuresis and increase in plasma renin activity (PRA) caused by loop diuretics; indomethacine, and possibly other NSAIDs with the exception of diflunisal, may also reduce the increase in urine volume caused by loop diuretics, possibly by inhibiting renal prostaglandin synthesis and/ or by causing sodium and fluid retention.
In addition, concurrent use of NSAIDs with a diuretic may increase the risk of renal failure secondary to a decrease in renal blood flow caused by inhibition of renal prostaglandin synthesis. In the premature neonate, administration of 1 mg/kg of frusemide immediately following indomethacin has been shown to prevent or reduce indomethacin-reduced adverse renal effects without interfering with ductus arteriosus closure.
Probenecid: Probenecid has been found to increase serum concentrations of frusemide by inhibiting active renal tubular secretion.