The ototoxic and nephrotoxic effects of other medications may be increased by concomitant administration of furosemide.
Some electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia) may increase the toxicity of certain drugs (e.g. drugs inducing QT interval prolongation syndrome such as amisulpride, atomoxetine, pimozide, sotalol, sertindole).
There is increased risk of hypokalaemia when furosemide is used in combination with beta-2 sympathomimetics in large doses, theophylline, corticosteroids, liquorice, carbenoxolone, prolonged use of laxatives, reboxetine, or amphotericin.
Furosemide may sometimes attenuate the effect of other drugs e.g. the effect of anti-diabetics and of pressor amines.
Probenecid, methotrexate (see Cytotoxic agents) and other drugs which, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide. Conversely, furosemide may decrease renal elimination of these drugs. In case of high-dose treatment (in particular, of both furosemide and the other drugs), this may lead to increased serum levels and an increased risk of adverse effects due to furosemide or the concomitant medication.
Cardiac glycosides: The potassium loss caused by potassium depleting diuretics such as furosemide increases the toxic effects of digoxin and other digitalis glycosides.
Anti-arrhythmic drugs: Hypokalaemia caused by loop diuretics may increase the cardiac toxicity of anti-arrhythmic drugs such as amiodarone, disopyramide, flecainide, quinidine and sotalol, and may antagonise the effects of lidocaine and mexiletine.
Antihypertensive drugs: The dosage of concurrently administered diuretics, antihypertensive agents or other drugs with blood pressure lowering potential may require adjustment as a more pronounced fall in blood pressure must be anticipated if given with furosemide. A marked fall in blood pressure and deterioration in renal function may be seen when angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists are added to furosemide therapy, or when the dosage is increased. The dose of furosemide should be reduced for at least three days, or the drug stopped before initiation of ACE-inhibitor or angiotensin II receptor antagonist therapy, or before their dose is increased.
Lithium: In common with other diuretics, serum lithium levels may be increased when furosemide is given to patients stabilised on this therapy, resulting in increased lithium toxicity (cardiotoxicity, neurotoxicity). It is recommended that lithium levels are carefully monitored and where necessary the lithium dosage adjusted during concurrent use.
Risperidone: Caution should be exercised and the risks and benefits of the combination or co-treatment with furosemide or with other potent diuretics should be considered prior to the decision to use. Concomitant use with risperidone in elderly patients with dementia should be avoided.
Non-steroidal anti-inflammatory drugs: Certain NSAIDs (including indomethacin, ketorolac, acetylsalicylic acid) may decrease the effectiveness of furosemide and may cause acute renal failure in cases of pre-existing hypovolaemia or dehydration. Salicylate toxicity may be increased by furosemide.
Antibiotics: Furosemide may potentiate the nephrotoxicity and ototoxicity of aminoglycosides and other ototoxic drugs. Since this may lead to irreversible damage, these drugs must only be used with furosemide when there are compelling medical reasons.
There is an increased risk of ototoxicity when loop diuretics are given with vancomycin or polymyxins (colistin).
Impairment of renal function may develop in patients receiving concurrent treatment with furosemide and high doses of certain cephalosporins (e.g. cephaloridine).
Cytotoxic agents: There is a risk of ototoxicity if cisplatin and furosemide are given concurrently. Low doses of furosemide (e.g. 40 mg in patients with normal renal function) should be used and a positive fluid balance maintained when furosemide is used to achieve forced diuresis during cisplatin treatment to reduce the risk of additional nephrotoxicity.
Methotrexate and other drugs which, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide. Conversely, furosemide may decrease renal elimination of methotrexate. This may lead to increased serum levels and increased risk of adverse events, especially with high dose therapy of methotrexate or furosemide.
Ciclosporin: Concomitant use of ciclosporin and furosemide is associated with an increased risk of gouty arthritis.
Anti-convulsants: Phenytoin may decrease the effectiveness of furosemide. Concomitant administration of carbamazepine may increase the risk of hyponatraemia.
Corticosteroids: Concurrent use of corticosteroids may cause sodium retention and increased risk of developing hypokalaemia.
Chloral hydrate/Triclofos: Bolus doses of intravenous furosemide may induce flushing, sweating, tachycardia and variations in blood pressure in patients receiving chloral hydrate or triclofos.
Neuromuscular blocking agents: Furosemide may affect the response to neuromuscular blocking agents (increased or decreased effect).