Not recommended combinations: Lithium: Lithium excretion levels may be reduced by furosemide, resulting in increased cardiotoxic effect and lithium toxicity. Therefore, this combination is not recommended. If this combination is deemed necessary lithium levels should be carefully monitored and lithium dosage should be adjusted.
Combinations requiring a caution for use: Drugs with an increased risk of QTc-prolongation and torsades-de-pointes linked to hypokalaemia: Furosemide-induced electrolyte disturbances (hypokalaemia, hypomagnesaemia and hypocalcaemia) can cause QTc prolongation and therefore the risk of arrhythmias is increased when concomitantly given with active substances that prolong the QT interval or produce hypokalaemia like: class I and class III antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide); cardiac glycosides (digoxin), concurrent administration of furosemide increases cardiac toxicity of cardiac glycosides and may lead to fatal arrhythmias; antipsychotics (like sultopride, phenothiazines [e.g. chlorpromazine, thioridazine, trifluoperazine], benzamides [amisulpride, sulpiride], butyrophenones [e.g. droperidol, haloperidol]); other neuroleptics (pimozide); other miscellaneous substances (e.g. bepridil, cisapride, erythromycin, halofantrine, sparfloxacine, pentamidine, quinolone etc.).
For this reason monitoring of potassium plasma levels and ECG should be made when these medicinal substances are prescribed concomitantly.
Medicinal substances decreasing serum potassium: Co-administration of furosemide with amphotericin B, glucocorticoids, carbenoxolone, tetracosactide, or laxatives may increase potassium loss. Liquorice has the same effect as carbenoxolone. In the association with glucocorticoids, hypokalaemia should be considered and its aggravation with the overuse of laxatives. Since this may lead to irreversible hearing damages, this combination should only be used if there are compelling medical reasons. Potassium levels should be monitored.
Medicinal substances decreasing serum sodium: Concomitant administration of carbamazepine or aminoglutethimide may increase the risk of hyponatraemia.
Non-steroidal anti-inflammatory agents and high doses of salicylates: Non-steroidal anti-inflammatory agents, (including coxibs) may induce acute renal failure in cases of pre-existing hypovolaemia and reduce the diuretic, natriuretic and antihypertensive effects of furosemide. When co-administered with high doses of salicylates, the predisposition for salicylic toxicity may be increased due to a reduced renal excretion or to a modified renal function.
Inhibitors of the angiotensin converting enzyme (ACE) and Angiotensin II antagonists (ARA): The hypotensive effects and/or renal effects are potentiated when concomitantly given with furosemide. Reduction or interruption of furosemide therapy is recommended at least three days before initiating administration of ACE inhibitors and ARAs. Renal impairment may also occur during the first concurrent administration, or with the first administration of high doses of an ACE inhibitor or of an antagonist of the angiotensin II receptor.
Drugs that increase the antihypertensive effect of furosemide: The effect of other certain anti-hypertensive agents (other diuretics and other drugs that lower blood pressure like beta-blocker) may be potentiated by concurrent administration of furosemide.
The potential for an additive effect between furosemide and amifostine, baclofen or alpha-blocker regarding hypotensive effects exists.
There is an increased risk of postural hypotension when loop diuretics like furosemide and tricyclic antidepressants (e.g. imipramine, nortriptyline, amitriptyline) or antipsychotic agents are given concomitantly.
Anti-diabetic agents: A decrease in glucose tolerance may occur, since furosemide may attenuate the effect of the anti-diabetic agents. Adjustment of the dose of antihyperglycaemic medications may be needed.
Chloral Hydrate: In isolated cases, the intravenous administration of furosemide in a 24 hour period prior to chloral hydrate administration may lead to flush, hyperhidrosis, anxiety, nausea, increase in blood pressure and tachycardia. Therefore, the simultaneous administration of furosemide and chloral hydrate is not recommended.
Fibrates: Blood levels of furosemide and of fibric acid derivates (such as clofibrate and fenofibrate) may be increased during concurrent administration (particularly in case of hypoalbuminaemia, e.g. in nephrotic syndrome). The increase of its effects (increased diuresis and muscle symptoms) should be monitored.
Iodinated contrast media: In patients with risk factors like raised S-creatinine levels, dehydration, congestive heart failure, age over 70 years old or concurrent administration of nephrotoxic drugs the concomitant administration of furosemide and iodinated contrast media may increase the risk of contrast media associated acute renal failure and should therefore be avoided.
Metformin: The blood levels of metformin may be increased by furosemide. Inversely, metformin may reduce furosemide concentration. The risk is linked to an increased occurrence of lactic acidosis in case of functional renal insufficiency.
Colestyramine and colestipol: These drugs may reduce furosemides bioavailability.
Nephrotoxic / ototoxic agents: Furosemide may intensify the nephrotoxic effects of nephrotoxic drugs (e.g. cephaloridine, cephalothin, ceftazidime, polymyxins, aminoglycosides, organoplatins, immunosuppressants, foscarnet, pentamidine).
Antibiotics like cephalosporins - impairment of renal function may develop in patients receiving treatment with furosemide and high doses of certain cephalosporins.
There is a risk of ototoxic effects if cisplatin and furosemide are given concomitantly. In addition, nephrotoxicity of cisplatin may be enhanced if furosemide is not given in low doses (e.g. 40 mg in patients with normal renal function) and with positive fluid balance, when used to achieve forced diuresis during cisplatin treatment.
Furosemide may also intensify the ototoxicity of certain drugs, for example aminoglycosides and antibiotics such as kanamycin, gentamicin and tobramycin, in particular in patients with renal impairment. Since this may lead to irreversible damage, these drugs must only be used with furosemide if there are compelling medical reasons.
Neuromuscular blocker: Small doses of furosemide (less than 100 μg/kg) may potentiate neuromuscular blockade of competitive neuromuscular blocker (curare-type muscle relaxants like atracurium and tubocurarine) and depolarising neuromuscular blocker (like succinylcholine), whereas high doses may result in antagonism of neuromuscular blockade. The potassium-depleting effect of diuretics may enhance the effect of competitive neuromuscular blocker.
Other diuretics (potassium-sparing such as amiloride, triamterene): Concurrent administration of furosemide and potassium-sparing diuretics may lead to a synergistic effect regarding diuresis. Sodium excretion may increase and potassium excretion may decrease.
Theophylline: Theophylline's clearance has been found to be decreased by around 20 % by concurrent administration of furosemide thereby potentiating the effects of theophylline. There is an increased risk of hypokalaemia when given concomitantly with furosemide.
Thiazides: A synergetic effect of diuresis, sodium and potassium excretion occurs as result of interaction of furosemide and thiazides resulting in an increased risk of dehydration, hyponatraemia and hypokalaemia.
Drugs that undergo significant renal tubular secretion: Probenecid, methotrexate and other drugs which, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide. Controversially, furosemide may decrease renal elimination of these substances. In case of high-dose treatment (in particular of both furosemide and the other substances), this may lead to increased serum levels and an increased risk of adverse effects due to furosemide or the concomitant medication.
Anticonvulsants: Attenuation of the effect of furosemide may occur following concurrent administration of anticonvulsants (e.g. phenytoin, phenobarbital).
Pressor amines (e.g. epinephrine, norepinephrine): Concomitant use of furosemide may attenuate the effects of pressor amines.
Other interactions: Concomitant use of ciclosporin and diuretics is associated with an increased risk of gouty arthritis and higher serum creatinine value in individuals.