POM: Prescription only medicine
This information is intended for use by health professionals
Special dosage recommendations:For adults, the dose is based on the following conditions: - Oedema associated to chronic and acute congestive heart failure The recommended initial dose is 20 to 40 mg daily. This dose can be adapted to the patient´s response, as necessary. The dose should be given in two or three individual doses per day for chronic congestive heart failure and as a bolus for acute congestive heart failure. - Oedema associated with renal disease The recommended initial dose is 20 to 40 mg daily. This dose can be adapted to the response as necessary. The total daily dose can be administered as a single dose or as several doses throughout the day. If this does not lead to an optimal fluid excretion increase, furosemide must be administered in continuous intravenous infusion, with an initial rate of 50 mg to 100 mg per hour. Before beginning the administration of furosemide, hypovolaemia, hypotension and acid-base and electrolytic imbalances must be corrected. In dialyzed patients, the usual maintenance dose ranges from 250 mg to 1,500 mg daily. In patients with nephrotic syndrome the dosage must be determined with caution, because of the risk of a higher incidence of adverse events. - Oedema associated with hepatic disease When intravenous treatment is absolutely needed, the initial dose should range from 20 mg to 40 mg. This dose can be adapted to the response as necessary. The total daily dose can be administered as a single dose or in several doses. Furosemide can be used in combination with aldosterone antagonists in cases in which these agents in monotherapy are not sufficient. In order to avoid complications such as orthostatic intolerance or acid-base and electrolytic imbalances or hepatic encephalopathy, the dose must be carefully adjusted to achieve a gradual fluid loss. The dose may produce in adults a daily body weight loss of approximately 0.5 kg. In cases of ascites with oedema, weight loss induced by enhanced diuresis should not exceed 1 kg / day.- Pulmonary oedema (in acute heart failure) The initial dose to be administered is 40 mg furosemide by intravenous application. If required by the condition of the patient, another injection of 20 to 40 mg furosemide is given after 30 60 minutes. Furosemide should be used in addition to other therapeutic measures.- Hypertensive crisis (in addition to other therapeutic measures) The recommended initial dose in hypertensive crisis is 20 mg to 40 mg administrated in bolus by intravenous injection. This dose can be adapted to the response as necessary.
Concomitant use with risperidoneIn risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97 years) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70-96 years) or furosemide alone (4.1%; mean age 80 years, range 67-90 years). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings. No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be avoided in elderly patients with dementia (see section 4.3 Contraindications).Photosensitivity: Cases of photosensitivity reactions have been reported. If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.
Furosemide 10 mg/ml Solution for Injection (2ml, 4ml and 5ml ampoule)This medicinal product contains less than 1 mmol sodium (23 mg) per ampoule i.e. essentially "sodium free.
Furosemide 10 mg/ml Solution for Injection (25 ml vial)This medicinal product contains approximately 93 mg of sodium per vial. To be taken into consideration by patients on a controlled sodium diet.
Not recommended combinationsLithium: Lithium excretion levels may be reduced by furosemide, resulting in increased cardiotoxic effect and lithium toxicity. Therefore, this combination is not recommended (see section 4.4). If this combination is deemed necessary lithium levels should be carefully monitored and lithium dosage should be adjusted. 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.
Combinations requiring a caution for useOtotoxic drugs (e.g. aminoglycosides, cisplatin): Furosemide may intensify the ototoxicity of certain drugs, for example cisplatin or aminoglycoside 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. 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. Carbamazepine and aminoglutethimide: Concomitant administration of carbamazepine or aminoglutethimide may increase the risk of hyponatraemia. Other anti-hypertensive agents: The effect of other certain anti-hypertensive agents (diuretics and other drugs that low blood pressure) may be potentiated by concurrent administration of furosemide. Inhibitors of the angiotensin converting enzyme (ACE) and Angiotensin II receptor antagonists: The effects of other antihypertensives can be potentiated by concomitant administration of furosemide. Severe fall in blood pressure with shock in extreme cases and deterioration of renal function (acute renal failure in isolated cases) have been observed in combination with ACE inhibitors, when the ACE inhibitor was administered for the first time, or for the first time at high dosage (first dose hypotension). If possible, furosemide therapy should be temporarily discontinued (or at least the dose reduced) for three days before therapy with an ACE inhibitor or an Angiotensin II receptor antagonists is initiated or the dose of an ACE inhibitor or Angiotensin II receptor antagonists is increased. Patients taking diuretics may suffer accentuated hypotension and deterioration of renal function; renal impairment may also occur during the first concurrent administration, or with the first administration of high doses of ACE or of an antagonist of the angiotensin II receptor. Thiazides: A synergetic effect of diuresis occurs as result of interaction of furosemide and thiazides. Anti-diabetic agents: A decrease in glucose tolerance may occur, since furosemide may reduce these drugs action. 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. Cardiac glycosides (e.g. digoxin) and other medicinal products that may cause prolongation of the QT-interval: A decrease of potassium levels may increase digitalis toxicity; for this reason, potassium levels should be monitored. Some electrolyte disturbances may increase the toxicity of certain concomitantly administered drugs that may cause prolongation of the QT interval. e.g. (class Ia antiarrhythmics and class III antiarrhythmics like amiodarone, sotalol, dofetilide, ibutilide and quinolones). Monitoring of potassium plasma levels and ECG are recommended. Fibrates: Blood levels of furosemide and of fibric acid derivates (for example clofibrate and fenofibrate) may be increased during concurrent administration (particularly in case of hypoalbuminaemia). The increase of its effect/toxicity should be monitored. 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 its diuretic, natriuretic and antihypertensive effect. 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. Nephrotoxic drugs (e.g. polymyxins, aminoglycosides, cephalosporins organoplatins, immunosuppressants, iodinated contrast media, foscarnet, pentamidine): Furosemide may intensify the nephrotoxic effects of nephrotoxic drugs.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 cytotoxic effects if cisplatin and furosemide are given concomitantly.In addition, Nephrotoxicity of cisplatin may be enhanced if furosemide in 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. 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. Conversely, furosemide may decrease renal elimination of these products. In case of high-dose treatment (in particular, of both furosemide and the other medicinal products), this may lead to increased serum levels and an increased risk of adverse effects due to furosemide or the concomitant medication. Peripheral adrenergic inhibitors: These agents´ effects may be enhanced by the simultaneous administration of furosemide. Phenobarbital and phenytoin: Attenuation of the effect of furosemide may occur following concurrent administration of these drugs. Tubocurarine, curarine derivatives and succinyl choline: The muscle relaxing effect of these agents may be enhanced or prolonged by furosemide.Glucocorticoids, carbenoxolone, Amphotericin B, Penicillin G, ACTH, laxatives and liquorice: Co-administration of furosemide with glucocorticoids, carbenoxolone,large amount of liquorice or prolonge use of laxatives may increase potassium loss. 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. Sucralfate:Simultaneous administration of sucralfate and furosemide may reduce the natriuretic and antihypertensive effects of furosemide. Patients receiving both drugs should be observed closely to determine if the desired diuretic and/or antihypertensive effect of furosemide is achieved. The intake of furosemide and sucralfate should be separated by at least two hours.Oral anticoagulants:Furosemid increases the effects of oral anticoagulants.Theophylline: The effects of theophylline and of curare-type muscle relaxants may be potentiated. Pressor amines (e.g. adrenaline (epinephrine), noradrenaline (norepinephrine)): Concomitant use of furosemide may attenuate the effects of pressor amines. Other interactions: Concomitant use of ciclosporin and furosemide is associated with increased risk of gouty arthritis.
Blood and lymphatic system disordersUncommon: thrombocytopenia; thrombocytopenia may become manifest, especially with an increase of haemorrhage tendency. Rare: eosinophilia, leukopenia, bone marrow depression; occurrence of this symptom necessitates withdrawal of treatment. Very rare: haemolytic anaemia, aplastic anaemia, agranulocytosis. Severe fluid depletion may lead to haemoconcentration with a tendency for thromboses to develop especially in elder patients.
Immune system disordersRare: severe anaphylactic and anaphylactoid reactions such as anaphylactic shock (for treatment see section 4.9).
Endocrine disordersGlucose tolerance may decrease with furosemide. In patients with diabetes mellitus this may lead to a deterioration of the metabolic control; latent diabetes mellitus may become manifest.
Metabolism and nutrition disordersHypokalaemia, hyponatraemia and metabolic alkalosismay occur, especially after prolonged therapy or when high doses are administered. Regular monitoring of serum electrolytes (especially potassium, sodium and calcium) is therefore indicated. Potassium depletion may occur, especially due to poor potassium diet. Particulary when the supply of potassium is concomitantly reduced and/or extrarenal potassium losses are increased (e.g. in vomiting or chronic diarrhoea) hypokalaemia may occur as a result of increased renal potassium losses. Underlying disorders (e.g. cirrhotic disease or heart failure), concomitant medication (see section 4.5) and nutrition may cause predisposition to potassium deficiency. In such cases, adequate monitoring is necessary as well as therapy substitution. As a result of increased renal sodium losses, hyponatraemia with corresponding symptoms may occur, particularly if the supply of sodium chloride is restricted. Increased renal calcium losses can lead to hypocalcaemia, which may induce tetania in rare cases. In patients with increased renal magnesium losses, tetania or cardiac arrhythmias were observed in rare cases as a consequence of hypomagnesaemia. Uric acid levels may increase and gout attacks may occur. Metabolic alkalosis may develop, or pre-existing metabolic alkalosis (for e.g. decompensated hepatic cirrhosis) may become more severe with furosemide.
Nervous system disordersRare: paraesthesia, vertigo, dizziness, sleepiness, confusion, sensations of pressure in the head.Not known: Dizziness, fainting and loss of consciousness (caused by symptomatic hypotension)
Eye disordersRare: aggravation of myopia, blurred vision; disturbances of vision with hypovolaemia symptoms.
Ear and labyrinth disordersRare: dysacusis and/or syrigmus (tinnitus aurium) due to furosemide are rare and usually transitory; incidence is higher in rapid intravenous administration, particularly in patients with renal failure or hypoproteinaemia (e.g. in nephrotic syndrome).Uncommon: deafness (sometimes irreversible)
Cardiac disordersIn particular, at the initial state of treatment and in elderly, a very intense diuresis may cause a reduction in blood pressure which, if pronounced may cause signs and symptoms such as orthostatic hypotension, acute hypotension, sensations of pressure in the head, dizziness, circulatory collapse, thrombophlebitis or sudden death (with i.m. or i.v. administration).
Gastrointestinal disordersRare: nausea, vomiting, diarrhoea, anorexia, gastric distress, constipation, dry mouth.
Hepato-biliary disordersVery rare: acute pancreatitis, intrahepatic cholestasis, cholestasis jaundice, hepatic ischaemia, increases in hepatic transaminases.
Skin and subcutaneous tissue disordersUncommon: pruritus, dermal and mucosal reactions (e.g. bullous exanthema, rash, urticaria, purpura, erythema multiforme, exfoliative dermatitis, photosensitivity) Rare: vasculitis, lupus erythematosus exacerbation or activation.Not known: acute generalised exanthematous pustulosis (AGEP)
Musculoskeletal and connective tissue disordersRare: leg muscle cramps, asthenia. chronic arthritis.
Renal and urinary disordersDiuretics may exacerbate or reveal acute retention of urine symptoms (bladder-emptying disorders, prostatic hyperplasia or narrowing of the urethra), vasculitis, glycosuria, transitorily increase of blood creatinine and urea levels. Rare: interstitial nephritis.
Pregnancy, puerperium and perinatal conditionsPremature infants treated with furosemide may develop nephrocalcinosis and/or nephrolithiasis; due to calcium deposit in renal tissue. In premature infants with respiratory distress syndrome, diuretic treatment in the first weeks of life with furosemide can increase the risk of persistent ductus arteriosus Botalli.
General disorders and administration site conditionsRare: febrile conditions; following i.m. injection local reactions such as pain may appear.
InvestigationsRare: serum cholesterol and triglyceride levels may rise during furosemide treatment.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Symptoms:Symptoms of these disturbances include severe hypotension (progressing to shock), acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy and confusion.
Treatment:At the first signs of shock (hypotension, sudoresis, nausea, cyanosis) the injection should be immediately interrupted, place the patient head down and allow free breathing. Fluid replacement and correction of the electrolyte imbalance; monitoring of metabolic functions, and maintenance of urinary flux. Medicinal treatment in case of anaphylactic shock: dilute 1 ml of 1:1000 adrenaline solution in 10 ml and inject slowly 1 ml of the solution (corresponding to 0.1 mg of adrenaline), control pulse and tension and monitor eventual arrhythmias. Adrenaline administration may be repeated, if necessary. Subsequently, inject intravenously a glucocorticoid (for example 250 mg of methylprednisolone), repeating if necessary. Adapt the above-mentioned dosages for children, according body weight. Correct hypovolaemia with available means and complement with artificial ventilation, oxygen and in case of anaphylactic shock with anti-histamines. No specific antidote to furosemide is known. If overdose during parenteral treatment has taken place, in principle the treatment consists on follow up and supportive therapy. Haemodialysis does not accelerate furosemide elimination.
DistributionFurosemide distribution volume is 0.1 to 1.2 litres per kg of body weight. The distribution volume may be increased depending on the concomitant illness. Protein binding (mostly to albumin) is higher than 98%.
EliminationFurosemide is mostly eliminated as the non-conjugated form, mainly through secretion at the proximal tube. After intravenous administration, 60% to 70% of furosemide is eliminated by this manner. The glucuronic metabolite of furosemide represents 10% to 20% of the recovered substances in the urine. The remaining dose is eliminated in the faeces, probably after biliary secretion. After intravenous administration, the plasma half-life of furosemide ranges from 1 to 1.5 hours. Furosemide is excreted in breast milk. It crosses the placental barrier transferring itself slowly to the foetus. Furosemide achieves similar concentrations in the mother, foetus and newborn.
Renal impairmentIn case of renal impairment, furosemide´s elimination is slower and its half-life is increased. In patients with end-stage renal disease the average half-life is 9.7 hours. In several multi-organ failure the half life may range from 20-24 hours. In case of nephrotic syndrome, the lower concentration of plasma proteins leads to higher concentrations of unbound furosemide . On the other hand, the efficiency of furosemide is reduced in these patients, due to intratubular albumin binding and to reduced tubular secretion. Furosemide exhibits low dialysis in patients undergoing haemodialysis, peritoneal dialysis or CAPD (Chronic Ambulatory Peritoneal Dialysis).
Hepatic impairmentIn case of hepatic impairment, furosemide´s half-life increases 30% to 90%, mainly due to the higher distribution volume. Biliary elimination might be reduced (up to 50%). In this group of patients, there is a wider variability of the pharmacokinetic parameters.
Congestive heart failure, severe hypertension, elderlyFurosemide elimination is slower due to reduced renal function in patients with congestive heart failure, severe hypertension or in elderly.
Premature infants and new-bornDepending on the maturity of the kidney, elimination of furosemide may be slow. In case of children with insufficient capacity of glucuronidation, the metabolism of the drug is also reduced. In term neonates the half-life is generally less than 12 hours.
Sage House, 319 Pinner Road, North Harrow, Middlesex, HA1 4HF, UK
+44 (0)208 8631 427
+44 (0)208 861 4867
+44 (0)1271 385257
0800 373 573