Furosemide 20mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Furosemide 20mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Furosemide BP 20mg
For excipients, see 6.1
3 PHARMACEUTICAL FORM
Oral - tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Furosemide tablets are recommended for use in all indications when prompt diuresis is required.
Indications include cardiac, pulmonary, hepatic, renal and peripheral oedema and oliguria due to chronic renal failure or insufficiency.
Furosemide may be effective in patients unresponsive to thiazide diuretics.
Furosemide is also used in the treatment of hypertension, either alone or with other antihypertensive agents and in the urgent treatment of hypercalcaemia to promote urinary excretion following rehydration.
4.2 Posology and method of administration
For oral administration OEDEMA
Adults & Elderly
Initially 40mg in the morning adjusted according to response; maintenance 20mg daily or 40mg on alternate days, increased in resistant oedema to 80mg or more as one or two doses daily or intermittently. Severe cases may require titration of the furosemide dosage up to 600mg daily.
Children
1-3mg/kg body weight daily up to a maximum of 40mg daily.
OLIGURIA
Adults & Elderly
Initially 250mg daily; if necessary larger doses, increasing in steps of 250mg, may be given every 4-6 hours to a maximum of a single dose of 2g (rarely used).
HYPERTENSION
Adults & Elderly
40-80mg daily by mouth alone or with other antihypertensive agents.
4.3 Contraindications
• Hypersensitivity to furosemide or any of the excipients, sulphonamides, sulphonamide derivatives/amiloride
• Anuria and impaired renal function (creatinine clearance below 30mL/min per 1.73 m2 body surface area) and renal failure resulting from poisoning by nephrotoxic and/or hepatotoxic agents
• Electrolyte disturbances (severe hyponatraemia: severe hypokalaemia), dehydration and/or hypotension (see section 4.4)
• Pre-coma/coma associated with hepatic cirrhosis
• Addison’s disease
• Digitalis intoxication (see also section 4.5)
• Breast-feeding women (see section 4.6)
4.4 Special warnings and precautions for use
Hypotension, hypovolaemia and/or dehydration (see also section 4.3)
These and any acid-base disturbances should be corrected before furosemide is started. If these occur during treatment, temporary discontinuation of furosemide infusion may be required.
Not recommended:
Furosemide is not recommended for use as diuresis as part of the preventative measures against radiocontrast-induced nephropathy in patients who are at high risk of developing this condition.
Dose titration/adjustment (see section 4.2)
• Furosemide should be shopped (or dose reduced) before starting an ACE-inhibitor)
• Patients with hypoproteinaemia (such as that associated with the nephritic syndrome) require careful dose titration (reduced furosemide effect: increased risk of ototoxicity)
• In moderate liver congestion dosage adjustment may be needed (see also section 4.3)
Caution required
Caution needed in the following circumstances:
• impaired hepatic function (see sections 4.2 & 4.3 and below- monitoring required)
• impaired renal function and hepato-renal syndrome (see section 4.3 and below-monitoring required)
• diabetes mellitus (latent diabetes may become overt: insulin requirements in established diabetes may increase)
• elderly patients (see section 4.2: increased risk of thiamine deficiency see below)
• difficulty with micturition/potential obstruction in the urinary tract including prostatic hypertrophy (increased risk of acute retention)
• patients who are at risk from a pronounced fall in blood pressure
• patients at particular risk of hypokalaemia (severe or congestive heart failure: hepatic cirrhosis - see also section 4.3: hyperaldosteroidism - see also section 4.3)
• gout (increased risk of hyperuricaemia)
• pancreatitis/history of pancreatitis (increased risk of recurrence/exacerbation with high doses- see also section 4.8)
• Systemic Lupus Erythematosus (SLE)/or a history of SLE (potential activation/aggravation of SLE)
• patients with hypoparathyroidism (risk of hypocalcaemic tetany)
• Premature infants nephrocalcinosis /nephrolithiasis (see below - monitoring required) in association with increased calcium excretion during long-term furosemide treatment;
• porphyria (although furosemide is probably non-porphyrogenic)
Thiamine deficiency
Prolonged treatment with furosemide can lead to thiamine deficiency, particularly in congestive heart failure or the elderly.
Caution with other medicines (also see section 4.5)
• Risperidone (use in elderly patients with dementia):
In 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.
• Beta2-agonists (asthma)
Hypokalaemia associated with beta2-agonists can be potentiated by furosemide.
Clinical monitoring requirements (see also section 4.8)
Regular monitoring for:
• blood dyscrasias. If these occur, stop furosemide immediately.
• liver damage
• idiosyncratic reactions
In infants there is a risk of
• development of nephrocalcinosis/nephrolithiasis in premature infants. Renal function must be monitored and renal ultrasonography performed.
• Persistence of patient ductus arteriosus
Laboratory monitoring requirements
• serum electrolytes (particularly sodium, potassium, indicators of acid-base disturbances) with replacement as appropriate
• frequent BUN/creatinine in first few months of treatment, periodically thereafter
Other alterations in lab values
• Serum creatinine and urea levels tend to rise during treatment
• Serum cholesterol and triglycerides may rise but usually return to normal within 6 months of starting furosemide
• Furosemide should be discontinued before a glucose tolerance test
Sugar intolerance
Patients with rare hereditary galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5. Interaction with other medicinal products and other forms of interaction
Alcohol: Enhanced hypotensive effect. Orthostatic hypotension, associated with diuretics, may be enhanced.
Aldesleukin: Enhanced hypotensive effect.
Anaesthetics, general: Enhanced hypotensive effects.
Anion-exchange resins: Colestyramine and colestipol markedly reduce the absorption of fUrosemide. Administer 2 to 3 hours apart.
Anti-arrhythmics: Toxicity of amiodarone, disopyramide, flecainide and quinidine is increased if hypokalaemia occurs. Action of lidocaine and mexilitine is antagonised by hypokalaemia. Hypokalaemia increases risk of ventricular arrhythmias with sotalol, a beta-blocker.
Antibacterials: Furosemide may enhance the toxicity of nephritic antibiotics, including some cephalosporins. Furosemide may potentiate the ototoxicity of aminoglycosides, vancomycin and other ototoxic agents. Since this may lead to permanent damage, these drugs must only be used with furosemide if there are compelling medical reasons.
Anticoagulants: Reduced anticoagulant effect when furosemide used concomitantly with warfarin.
Antidepressants: Increased risk of postural hypotension with tricyclic antidepressants. Enhanced hypotensive effect with monoamine oxidase inhibitors (MAOIs). Increased risk of hypokalaemia when furosemide and reboxetine used concomitantly.
Antidiabetics: The hypoglycaemic effect is antagonised by loop diuretics.
Antiepileptics: Increased risk of hyponatraemia with concomitant carbamazepine. The diuretic effect of furosemide has been shown to be substantially reduced by concomitant phenytoin therapy.
Antifungals: Increased risk of hypokalaemia with loop diuretics and amphotericin.
Anti-gout:Probenecid has been shown to reduce the renal clearance of furosemide and may increase, decrease or have no effect on the overall diuresis. In case of high-dose treatment (with furosemide and probenecid), this may lead to increased serum levels and an increased risk of adverse effects.
Antihistamines: Hypokalaemia increases risk of ventricular arrhythmias with terfenadine.
Antihypertensives: Furosemide enhances the hypotensive action of other antihypertensive drugs, including beta-blockers, calcium-channel blockers and hydralazine. The dosage of currently administered antihypertensive agents may require adjustment. There is an increased risk of first-dose hypotension with alpha blockers such as prazosin or angiotensin-converting enzyme (ACE) inhibitors such as captopril. Particular care should be taken with ACE inhibitors and angiotensin-II antagonists when initiating or increasing their dose in concomitant therapy with furosemide, since combination can result in marked reduction in blood pressure and deterioration in renal function. The dose of furosemide should be reduced for at least three days, or the drug stopped, before initiating or increasing the dose of an ACE inhibitor or angiotensin II receptor agonist. Long term intensive treatment with captopril can enhance the natriuretic response to furosemide.
Antipsychotics: Hypokalaemia increases risk of ventricular arrhythmias with pimozide and sertindole, concurrent use should be avoided. Enhanced hypotensive effect with phenothiazines. 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: Increased risk of toxicity if hypokalaemia or hypomagnesaemia occurs. The cardiac glycoside dosage may require adjustment as a more pronounced fall in blood pressure must be anticipated if given concomitantly with furosemide.
Corticosteroids: The increased risk of hypokalaemia occurs particularly with the naturally-occurring corticosteroids such as cortisone and hydrocortisone. The synthetic corticosteroids have a much less marked potassium-losing effect. Fluid retention associated with corticosteroid use may cause antagonism of diuretic/antihypertensive effect. Concomitant administration of corticosteroids may cause sodium retention.
Cytotoxics: 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 does (e.g. 40mg in patients with normal renal function) and with positive fluid balance when used to achieve forced dieresis during cisplatin treatment.
Diuretics: Increased risk of hypokalaemia with other loop diuretics and other diuretics, including acetazolamide and thiazides. Severe electrolyte disturbances may occur in patients given metolazone concurrently with furosemide. The dosage of concurrently administered diuretics may require adjustment as a more pronounced fall in blood pressure must be anticipated if given concomitantly with furosemide
Dompaminergics: Enhanced hypotensive effect with levodopa.
Immunosuppressants: Ciclosporin: conocmitant use of ciclosporin and furosemide is associated with increased risk of gouty arthritis.
Laxatives: Prolonged use may increase the risk of developing hypokalaemia.
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. It is recommended that lithium levels are carefully monitored and where necessary the lithium dosage is adjusted in patients receiving this combination.
Muscle relaxants: Enhanced hypotensive effect may occur with tizanidine.; effects of curare-type muscle relaxants may be potentiated.
Nicotine: Nicotine inhibits diuresis and diminishes the diuretic effect of furosemide. Nitrates: Enhanced hypotensive effect.
Nonsteroidal anti-inflammatory agents (NSAIDs): Certain NSAIDs (e.g. indometacin, ketorolac, acetylsalicylic acid), may attenuate the diuretic effect of furosemide and may cause acute renal failure in cases of pre-existing hypovolaemia or dehydration. Enhanced salicylate toxicity or nephrotoxicity of NSAIDs.
Prostaglandins: Hypotensive effect may be potentiated by alprostadil.
Sympathomimetics: There is an increased risk of hypokalaemia with high doses of 02-sympathomimetics. Effects of pressor amines may be attenuated.
Theophylline: Risk of hypokalaemia may be increased; effects of theophylline may be potentiated.
Ulcer healing drugs: Carbenoloxone and liquorice may increase risk of hypokalaemia Fluid retention associated with carbenoxolone may cause antagonism of diuretic/antihypertensive effect. Ranitidine causes a moderate increase in the bioavailability of furosemide.
4.6 Pregnancy and lactation
Furosemide must not be used during pregnancy unless there are compelling medical reasons.
In humans, there is clinical evidence of the safety of the drug in the third trimeseter of human pregnancy; however, furosemide crosses the placental barrier and animal teratology studies indicate it can cause foetal abnormalities.
As a potent diuretic furosemide will reduce maternal blood volume and could compromise placental perfusion. If treatment is considered essential, foetal growth should be monitored.
Furosemide is not recommended in nursing mothers as it passes into breast milk and may inhibit lactation.
4.7 Effects on ability to drive and use machines
Reduced mental alertness may impair ability to drive or operate dangerous machinery.
4.8 Undesirable effects
Metabolism and nutrition disorders: The most common side-effect is fluid and electrolyte imbalance including hyponatraemia, hypokalaemia, hypochloraemic alkalosis, hypotension and increased calcium excretion.
As with other diuretics, electrolyte and water balance may be disturbed as a result of diuresis after prolonged therapy. Furosemide leads to an increased excretion of sodium and chloride and consequently water. In addition, excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased. Symptomatic electrolyte disturbances and metabolic alkalosis may develop in the form of a gradually increasing electrolyte deficit or, for example, where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses. Warning signs of electrolyte disturbances include increased thirst, dry mouth, headache, hypotension, drowsiness, confusion, muscle cramps, muscle weakness, tetany, weakness, disorders of cardiac rhythm and gastrointestinal symptoms.
Increased calcium excretion in infants and new-borns has been associated with reports of decreased bone mineral content, rickets, fractures and renal calcification. Hypocalcaemic tetany has also been reported in hypoparathyroid patients. Nephrocalcinosis /nephrolithiasis may develop in premature infants.
Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment.
Thiamine deficiency with prolonged treatment, particularly in congestive heart failure and the elderly.
Furosemide may cause hyperuricaemia and precipitate attacks of gout in some patients.
Serum cholesterol and triglyceride levels may rise during furosemide treatment.
During long term therapy they will usually return to normal within six months.
Nervous system disorders: Rarely, paraesthesiae may occur
Ear and labyrinth disorders: Tinnitus and deafness occur rarely and are usually associated with large and/or rapidly administered parenteral doses, or in patients with hypoproteinaemia or renal impairment. They are usually transient but deafness may be permanent, particularly if furosemide is used concurrently with other ototoxic drugs.
Disorders of the eye: Blurred vision, yellow vision
Disorders of the immune system: Hypersensitivity reactions, that may include skin rashes, photosensitivity, vasculitis, fever, urticaria and interstitial nephritis, occur rarely but when these occur treatment should be withdrawn. Severe anaphylaxis or_anaphylactoid reactions (e.g with shock) may also occur rarely and necessitate immediate withdrawal of furosemide treatment.
Endocrine disorders: Glucose tolerance may decrease with Furosemide. In patients with diabetes mellitus this may lead to a deterioration of metabolic control with hyperglycaemia and glycosuria. Latent diabetes may also become manifest.
Vascular disorders: Furosemide may cause a reduction in blood pressure which, if pronounced, may cause signs and symptoms such as impairment of concentration and reactions, light-headedness, sensations of pressure in the head, headache, dizziness, drowsiness, syncope, weakness, disorders of vision, dry mouth, and orthostatic hypotension. The diuretic action of furosemide may lead to or contribute to hypovolaemia and dehydration, especially in elderly patients. Severe fluid depletion may lead to haemoconcentration with a tendency for thromboses to develop.
Gastrointestinal disorders: side-effects of a minor nature such as nausea, or gastric upset (vomiting and diarrhoea) may occur but are not usually severe enough to necessitate withdrawal of treatment. Pancreatitis is more common at high doses.
Blood and lymphatic system disorders: In rare cases, thrombocytopenia, leucopenia, agranulocytosis, eosinophilia, aplastic anaemia or haemolytic anaemia may develop. Bone marrow depression necessitates withdrawal of treatment.
Hepatobiliary disorders: In isolated cases, intrahepatic cholestasis, an increase in liver transaminases, or cholestatic jaundice has been reported. Hepatic encephalopathy in patients with hepatocellular insufficiency may occur.
Skin and subcutaneous tissue disorders: Skin rashes and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, and other rashes. Rarely these may be severe and may include, purpura and exfoliative dermatitis and bullous lesions such as erythems multiforme and pemphigoid
Renal and urinary disorders: Increased production of urine may provoke or aggravate complaints in patients with an obstruction of urinary outflow. Thus, acute retention of urine with possible secondary complications may occur, for example, in patients with bladder-emptying disorders, prostatic hyperplasia or narrowing of the urethra. As with other diuretics, treatment with furosemide may lead to transitory increases in blood creatinine and urea levels.
Pregnancy, puerperium and perinatal conditions: If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus.
General disorders and administration site conditions: malaise
4.9 Overdose
Toxicity
The toxicity of diuretics is principally associated with fluid and electrolyte loss. More than a few tablets could cause marked effects, particularly in the elderly, however, adults and children who have ingested less than 2 mg/Kg are unlikely to require medical assessment. Peak diuresis and effects on blood pressure are likely to occur within 2 hours of ingestion.
Features
Most patients will not develop serious symptoms but overdose may cause acute, profound diuresis (increased frequency of micturition) resulting in dehydration, volume depletion and electrolyte disturbance. Hypotension, tachycardia, cardiac arrhythmia, hypovolaemia, haemoconcentration hypokalaemia, hypomagnaesemia, hypocalcaemia, hyponatraemia and hypochloraemic alkalosis may occur, with electrolyte depletion causing symptoms such as severe hypotension (progressing to shock), acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy, weakness, dizziness, confusion, anorexia, lethargy, vomiting, cramps and dysrhythmias.
Dose related adverse effects during therapy have been reported. Myalgia, arthralgia, muscle cramps and weakness occurred in patients receiving doses of between 2 and 10 mg furosemide. High doses have the potential to cause transient deafness and disturbance of uric acid excretion precipitating gout.
Management
• The benefit of gastric decontamination is uncertain, however, activated charcoal (50g for adults; 1 g/Kg for children) should be considered if the patient presents within 1 hour of ingesting a toxic dose.
• Observe for a minimum of 4 hours. Monitor BP and pulse.
• Give i.v. fluids for hypotension and dehydration.
• Monitor urinary output and serum electrolyte levels including chloride and bicarbonate. Correct electrolyte imbalances.
• Perform a 12 lead ECG and measure the QRS duration and QT interval. Repeat 12 lead ECG is recommended, especially in symptomatic patients.
• Other measures as indicated by the patient's clinical condition.
• Patients should be advised on discharge to seek medical attention if symptoms subsequently develop.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Furosemide is a diuretic with a rapid action. It exerts inhibiting effects on electrolyte reabsorption in the proximal and distal renal tubules and in the ascending loop of Henle.
5.2 Pharmacokinetic properties
Furosemide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. It has a biphasic half-life in the plasma with a terminal elimination phase that has been estimated to range up to about 1/ hours. Furosemide is mainly excreted in the urine. Furosemide crosses the placental barrier and is excreted in milk.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to those included in other sections.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose Maize starch
Pregelatinised maize starch Magnesium stearate
6.2 Incompatibilities
None.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Do not store above 25°C Store in the original container
6.5 Nature and contents of container
Polypropylene or polyethylene containers or amber glass bottles containing 50, 100, 250, 500 and 1000 tablets.
Strip packs of opaque white or clear PCV film and 20 micron aluminium foil. The tablets are packed in multiple strips of 10 tablets i.e. 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100 tablets and in multiple strips of 14 tablets i.e. 14, 28, 56, 84 and 112 tablets.
Bulk pack of a plastic container containing 20000 tablets.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF U.K.
8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0099
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
09th June 1982 / 7th April 2008
10 DATE OF REVISION OF THE TEXT
27/09/2012