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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. hypokalaemia, 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 hypokalaemia 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
Cardiac glycosides – hypokalaemia and electrolyte disturbances (including hypomagnesia) 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 diures is possible when furosemide given with metolazone.
Increased risk of hypokalaemia 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. Indometacin 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. Salycylic toxicity may be increased by furosemide
Antibiotics – increased risk of ototoxicity with aminoglycosides, polymixins 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 hyponatraemia 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 hypokalaemia with reboxetine
Antidiabetics – hypoglycaemic effects antagonised by furosemide
Antiepileptics – increased risk of hyponatraemia with carbamazepine. Diuretic effect reduced by phenytoin.
Antihistamines – hypokalaemia with increased risk of cardiac toxicity
Antifungals – increased risk of hypokalaemia 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) – hypokalaemia increases the risk of ventricular arrhythmias
Corticosteroids – diuretic effect anatgonised (sodium retention) and increased risk of hypokalaemia
Glychyrrizin -(contained in liquorice) may and increase the risk of developing hypokalaemia.
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 ciclosprin and tacrolimus. Increased risk of gouty arthritis with ciclosporin
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 hyperkalaemia
Prostaglandins – enhanced hypotensive effect with alprostadil
Sympathomimetics – increased risk of hypokalaemia with high doses of beta2 sympathomimetics
Theophylline – enhanced hypotensive effect
Probenecid – effects of furosemide may be reduced by probenecid and furosemide may reduce renal clearance of probenecid.
Anaesthetic agents – general anaesthetic 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 hyponatraemia.
4.6 Fertility, pregnancy and lactation
Furosemide crosses the placental barrier and should not be given during pregnancy unless there are compelling medical reasons. It should only be used for the pathological causes of oedema which are not directly or indirectly linked to the pregnancy. The treatment with diuretics of oedema and hypertension caused by pregnancy is undesirable because placental perfusion can be reduced, so, if used, monitoring of fetal growth is required. However, furosemide has been given after the first trimester of pregnancy for oedema, hypertension and toxaemia of pregnancy without causing fetal or newborn adverse effects.
Breast-feeding (see section 4.3)
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