Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

General- The dosage of concurrently administered cardiac glycosides, diuretics, anti-hypertensive 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 concomitantly with furosemide.

The toxic effects of nephrotoxic drugs may be increased by concomitant administration of potent diuretics such as furosemide.

Some electrolyte disturbances (e.g., hypokalemia, hypomagnesaemia) may increase the toxicity of certain other drugs (e.g., digitalis preparations and drugs inducing QT interval prolongation syndrome).

Antihypertensives – enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors or Angiotensin II receptor antagonists can result in marked falls in blood pressure, furosemide should be stopped, or the dose reduced before starting an ACE-inhibitor or Angiotensin II receptor antagonists (see section 4.4) 
Antipsychotics – furosemide-induced hypokalemia increases the risk of cardiac toxicity. Avoid concurrent use with pimozide. Increased risk of ventricular arrhythmias with amisulpride or sertindole. Enhanced hypotensive effect with phenothiazines.

When administering 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. See section 4.4 Special warnings and precautions for use regarding increased mortality in elderly patients with dementia concomitantly receiving risperidone.

Anti-arrhythmic (including amiodarone, disopyramide, flecainide and sotalol) - risk of cardiac toxicity (because of furosemide-induced hypokalemia). The effects of lidocaine, tocainide or mexiletine may be antagonized by furosemide.

Cardiac glycosides – hypokalemia and electrolyte disturbances (including hypomagnesemia) increase the risk of cardiac toxicity.

Drugs that prolong Q-T interval – increased risk of toxicity with furosemide-induced electrolyte disturbances 
Vasodilators – enhanced hypotensive effect with moxisylyte (thymoxamine) or hydralazine.

Other diuretics – profound diuresis possible when furosemide given with metolazone. Increased risk of hypokalemia with thiazides.

Renin inhibitors – aliskiren reduces plasma concentrations of furosemide.

Nitrates – enhanced hypotensive effect.
Lithium - In common with other diuretics, serum lithium levels may be increased when lithium is given concomitantly with furosemide, resulting in increased lithium toxicity, including increased risk of cardiotoxic and neurotoxic effects of lithium.
Therefore, it is recommended that lithium levels are carefully monitored and where necessary the lithium dosage is adjusted in patients receiving this combination.

Chelating agents – sucralfate may decrease the gastro-intestinal absorption of furosemide – the 2 drugs should be taken at least 2 hours apart.

NSAIDs – increased risk of nephrotoxicity. Indomethacin and ketorolac may antagonise the effects of furosemide (avoid, if possible, see section 4.4). NSAIDs may attenuate the action of furosemide and may cause acute renal failure in cases of pre-existing hypovolaemia or dehydration.
Salicylates – effects may be potentiated by furosemide. Salicylic toxicity may be increased by furosemide.

Antibiotics – increased risk of ototoxicity with aminoglycosides, polymyxins or vancomycin - only use concurrently if compelling reasons. Increased risk of nephrotoxicity with aminoglycosides or cefaloridine. Furosemide can decrease vancomycin serum levels after cardiac surgery. Increased risk of hyponatremia with trimethoprim. Impairment of renal function may develop in patients receiving concurrent treatment with furosemide and high doses of certain cephalosporins.

Antidepressants – enhanced hypotensive effect with MAOIs. Increased risk of postural hypotension with TCAs (tricyclic antidepressants). Increased risk of hypokalemia with reboxetine

Antidiabetics – hypoglycemic effects antagonised by furosemide.

Antiepileptics – increased risk of hyponatremia with carbamazepine. Diuretic effect reduced by phenytoin.
Antihistamines – hypokalemia with increased risk of cardiac toxicity 
Antifungals – increased risk of hypokalemia and nephrotoxicity with amphotericin 
Anxiolytics and hypnotics – enhanced hypotensive effect. Chloral or triclorfos may displace thyroid hormone from  binding site.

CNS stimulants (drugs used for ADHD) – hypokalemia increases the risk of ventricular arrhythmias.
Corticosteroids – diuretic effect antagonized (sodium retention) and increased risk of hypokalemia.

Glychyrrizin -(contained in liquorice) may and increase the risk of developing hypokalemia.

Cytotoxics – increased risk of nephrotoxicity and ototoxicity with platinum compounds/cisplatin. 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.

Anti-metabolites – effects of furosemide may be reduced by methotrexate and furosemide may reduce renal clearance of  methotrexate.

Dopaminergics – enhanced hypotensive effect with levodopa.
Immunomodulators – enhanced hypotensive effect with aldesleukin. Increased risk of hyperkalaemia with cyclosporine and tacrolimus. Increased risk of gouty arthritis with cyclosporin
Muscle relaxants – enhanced hypotensive effect with baclofen or tizanidine. Increased effect of curare-like muscle relaxants.
Oestrogens – diuretic effect antagonised.
Progestogens (drosperidone) – increased risk of hyperkalemia.
Prostaglandins – enhanced hypotensive effect with alprostadil.
Sympathomimetics – increased risk of hypokalemia with high doses of beta 2 sympathomimetics.
Theophylline – enhanced hypotensive effect.
Probenecid – effects of furosemide may be reduced by probenecid and furosemide may reduce renal clearance of probenecid.
Anesthetic agents – general anesthetic agents may enhance the hypotensive effects of furosemide. The effects of curare may be enhanced by furosemide.

Alcohol – enhanced hypotensive effect.
Laxative abuse - increases the risk of potassium loss.
Others: Concomitant administration of aminoglutethimide may increase the risk of hyponatremia. products and others of i