Furosemide Tablets Bp 40mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Furosemide Tablets BP 40mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
40mg Furosemide B.P
3 PHARMACEUTICAL FORM
Tablet
Appearance: White circular flat bevelled edge 6.0mm tablet embossed PV on one face and F/40 on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
In the treatment of oedema associated with congestive heart failure, cirrhosis of the liver, renal disease including nephrotic syndrome.
In the treatment of peripheral oedema due to mild to moderate hypertension (alone, or in combination with other antihypertensive agents in the treatment of more severe cases)
Management of oliguria due to acute or chronic renal insufficiency
4.2 Posology and method of administration
Adults: The usual initial daily dose is 40 mg. This may require adjustment until the effective dose is achieved. In mild cases 20 mg daily or 40 mg on alternate days may be sufficient, whereas in cases of resistant oedema daily doses of 80 mg and above may be used as one or two doses daily, or intermittently. Severe cases may require gradual titration of the furosemide dosage up to 600 mg.
In patients with chronic renal insufficiency, an initial daily dose of 250 mg is employed. If a satisfactory diuresis is not produced then the dose may be increased in steps of 250 mg at four to six hourly intervals up to a maximum daily dose of 1,500 mg in 24 hours. In exceptional cases up to 2,000 mg in 24 hours may be given.
Children: The oral dose for children ranges from 1 - 3 mg/kg body weight daily, up to a maximum total dose of 40 mg per day.
Elderly: The usual adult dose, but caution is advised as furosemide is excreted more slowly in the elderly. Treatment should be started with 20mg and titrated upwards as required.
Method of administration: Oral - the tablets should be swallowed with water.
4.3 Contraindications
Furosemide is contraindicated in the presence of anuria, electrolyte deficiency, precoma associated with hepatic cirrhosis, digitalis intoxication, porphyria and hypersensitivity to furosemide or sulphonamides.
4.4. Special Warnings and Precautions for Use
Too vigorous diuresis may cause orthostatic hypotension or acute hypotensive episodes.
Where indicated, steps should be taken to correct hypotension or hypovolaemia before commencing therapy.
Caution is required in patients liable to electrolyte deficiency.
Regular monitoring of serum sodium, potassium and creatinine is generally recommended during furosemide therapy; particularly close monitoring is required in patients at high risk of developing electrolyte imbalances or in case of significant additional fluid loss. Hypovolaemia or dehydration as well as any significant electrolyte and acid-base disturbances must be corrected. This may require temporary discontinuation of furosemide.
Urinary output must be secured. Patients with partial obstruction of urinary outflow, for example, patients with prostatic hypertrophy or impairment of micturation have an increased risk of developing acute retention and require careful monitoring.
Particularly careful monitoring is necessary in:
• Patients with hypotension.
• Patients who are at risk from a pronounced fall in blood pressure
• Patients with latent or manifest diabetes. Furosemide may necessitate adjustment of control by hypoglycaemic agents in cases of diabetes mellitus.
• Patients with gout.
• Patients with hepatorenal syndrome
• Patients with hypoproteinaemia, e.g. associated with nephritic syndrome (the effect of furosemide may be weakened and its ototoxicity potentiated). Cautious dose titration is required.
• Premature infants (possible development nephrocalcinosis/nephrolithiasis; renal function must be monitored and renal ultrasonography performed).
• Hepatic failure and alcoholic cirrhosis particularly predispose to hypokalaemia and hypomagnesaemia.
The use of some diuretics is considered to be unsafe in acute porphyria, therefore caution should be exercised.
4.5. Interactions with other Medicaments and other forms of Interaction
Pharmacodynamic interactions of furosemide with other drugs:
An enhanced hypotensive effect may be seen when other antihypertensive (alpha-blockers, ACE inhibitors, angiotensin II receptor antagonists, beta-blockers), certain classes of antidepressants (MAOIs-Mono Amine Oxidase Inhibitors, TCAs-Tricyclic Antidepressants), phenothiazine antipsychotics and baclofen are given concomitantly with furosemide.
An increased risk of hypokalaemia may be seen when amphotericin, carbenoxolone, corticosteroids/ACTH (synthetic corticosteroids such as prednisolone have a less marked effect, corticosteroids/ACTH may also antagonise the diuretic effect and sodium retention), prolonged use of laxatives, liquorice, other diuretics (acetazolamide, thiazides and related diuretics), reboxetine, beta2 sympathomimetics, tacrolimus and theophylline are given concomitantly with furosemide.
Hypokalaemia and other electrolyte disturbances (including hypomagnaesaemia) caused by diuretics such as furosemide can increase the risk of toxicity inherent with other drugs or antagonise their actions;
The cardiac toxicity of digoxin, anti-arrhythmics (amiodarone, disopyramide, flecainide) and drugs that induce QT prolongation may be increased.
There is an increased risk of ventricular arrhythmias with certain antipsychotics (amisulpride, sertindole), atomoxetine and pimozide (avoid concomitant use).
The actions of lidocaine and mexiletine are antagonised.
There may be an increased risk of ototoxicity when furosemide is given with cisplatin, aminoglycosides, polymyxins and vancomycin. Co-administration of cisplatin or ciclosporin with furosemide can enhance nephrotoxicity and increase the risk of hypermagnaesaemia.
There may be an increased risk of hyponatraemia when furosemide is given with carbamazepine.
Aliskiren reduces furosemide plasma levels.
Furosemide antagonises the hypoglycaemic effect of hypoglycaemics.
There is an increased risk of nephrotoxicity due to NSAIDs when given with diuretics, while certain NSAIDs (especially indometacin and ketorolac) antagonise the diuretic effect of furosemide.
Phenytoin reduces the diuretic action of furosemide by up to 50% when given concomitantly.
Profound diuresis is possible when metolazone is given with furosemide.
Avoid the use of diuretics in lymecycline treatment.
There may be an increased risk of osteomalacia when diuretics are taken in combination with phenobarbital.
Pharmacokinetic interactions of furosemide with other drugs:
Furosemide decreases the excretion of lithium salts and may cause increased serum lithium levels, resulting in lithium toxicity. Therefore, it is recommended that lithium levels be carefully monitored.
Plasma concentrations of diuretics may be increased by antivirals (nelfinavir, ritonavir or saquinavir).
Plasma concentrations of diuretics may be decreased by barbiturates.
Probenecid, methotrexate and other drugs that, like furosemide, undergo significant renal tubular secretion may reduce the effect of furosemide. Conversely, furosemide may decrease the renal elimination of these drugs. In case of high-dose treatment (in particular, of both furosemide and the other drug), this may lead to increased serum levels and an increased risk of adverse effects due to furosemide or the concomitant medication.
4.6 Pregnancy and lactation
Furosemide has been given after the first trimester of pregnancy for oedema, hypertension and toxaemia of pregnancy without causing foetal or newborn adverse effects. However, it should only be given during pregnancy if strictly indicated and for short-term treatment.
As it may inhibit lactation and passes into breast milk, furosemide should be used with caution in nursing mothers.
4.7 Effects on ability to drive and use machines
Reduced mental alertness and rarely dizziness and blurred vision have been reported. Patients so affected should not drive or operate machines.
4.8. Undesirable Effects:
Disturbance of electrolytes and water balance (see section 4.4)
Furosemide leads to 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, e.g. where higher furosemide doses are administered to patients with normal renal function, acute severe electrolyte losses.
Warning signs of electrolyte disturbances include increased thirst, headache, confusion, muscle cramps, tetany, muscle weakness, disorders of cardiac rhythm and gastrointestinal symptoms.
The diuretic action of furosemide may lead to or contribute to hypovolaemia and dehydration, especially in elderly or dehydrated patients. Severe fluid depletion may lead to haemoconcentration with a tendency to thrombosis to develop. Furosemide may cause a reduction in blood pressure which, if pronounced may cause signs and symptoms such as impairment of concentrations and reactions, light-headedness, sensations of pressure in the head, headache, dizziness, drowsiness, weakness, disorders of vision, dry mouth, orthostatic intolerance. Bladder outlet obstruction:
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. Other blood biochemistry:
Treatment with furosemide may lead to transitory increases in blood creatinine and urea levels and to an increase in cholesterol and triglyceride serum levels. Serum levels of uric acid may increase and attacks of gout may occur.
Tetany and reduced serum calcium
Serum calcium levels may be reduced; in very rare cases tetany has been observed. Nephrocalcinosis / nephrolithiasis have been reported in premature infants.
Control of glucose:
Glucose tolerance may decrease with furosemide. In patients with diabetes mellitus this may lead to a deterioration of metabolic control, latent diabetes mellitus may become manifest.
Hearing disorders: Hearing disorders and tinnitus, although usually transitory, may occur in rare cases, particularly in patients with renal failure, hypoproteinaemia (e.g. in nephritic syndrome) and/or when intravenous furosemide has been given too rapidly.
Anaphylaxis and allergic reactions:
Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely.
The incidence of allergic reactions such as skin rash, photosensitivity, vasculitis, fever, interstitial nephritis or shock is very low but treatment should be withdrawn when these occur.
Skin and mucous membrane:
Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, erythema multiforme, exfoliate dermatitis, purpura.
Haematological
Aplastic anaemia and bone marrow depression has been reported as a rare complication and necessitate withdrawal of treatment.
Occasionally, thrombocytopenia may occur. In rare cases, leucopenia and eosinophilia may occur. In isolated cases, agranulocytosis, aplastic anaemia or haemolytic anaemia may develop.
Nervous system:
Rarely, paraesthesiae may occur.
Premature infants:
In premature infants furosemide may precipitate nephrocalcinosis/ nephrolithiasis. If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriousus. Others:
Gastrointestinal reactions such as nausea, vomiting or diarrhoea may occur. In isolated cases, intrahepatic cholestasis, an increase in liver transaminases or acute pancreatitis may develop.
4.9 Overdose
In cases of overdosage there is a danger of dehydration and electrolyte depletion due to excessive diuresis. Treatment should be aimed at fluid replacement and correction of electrolyte imbalance. Gastric lavage may be useful if ingestion is recent.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group:
High-ceiling diuretic sulphonamide- CO3C A01
Furosemide is one of the high ceiling diuretics, a term used to denote a group of diuretics that have a distinctive action on renal tubular function. The peak diuresis is far greater than that observed with other agents. The main site of action is the thick ascending loop of Henle where they inhibit electrolyte reabsorption. It increases renal blood flow without increasing the filtration rate. Such a change in renal haemodynamics reduces fluid and electrolyte reabsorption in the proximal tubule and may augment the initial diuretic response. Furosemide is an inhibitor of carbonic anhydrase but this activity is too weak to contribute to the proximal diuresis except when massive doses are employed. Furosemide enhances the excretion of both calcium and magnesium to an extent approximately proportional to the increase calcium re-absorption in the distal tubule. The calcuiric action of these agents is the basis for their use in symptomatic hypercalcemia.
It has been established that prostaglandin (PG) biosynthesis and the renin-angiotensin system are affected by furosemide administration and that furosemide alters the renal permeability of the glomerulus to serum proteins.
5.2 Pharmacokinetic Properties
Furosemide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. Bioavailability is about 65%. It has a biphasic half-life in plasma with a terminal elimination phase up to about 2 hours but this is prolonged in neonates, and in patients with hepatic and renal insufficiency. It is extensively bound to plasma proteins but is rapidly secreted by the organic acid transport system of the proximal tubule. In this manner it gains access to the tubular fluid and eventually to its site of action more distally. It is mainly excreted in the urine largely unchanged, but also in the form of glucuronide and free amine metabolites. Variable amounts are also excreted in the bile. Furosemide crosses the placental barrier and is excreted in milk. Non renal elimination is considerably increased in renal failure. The clearance of furosemide is not increased by haemodialysis.
5.3. Preclinical safety data
N/A
6.1 List of excipients
90.0mg
1.0mg
1.0mg
27.0mg
1.0mg
Lactose
Talc
Magnesium stearate Maize starch Colloidal Silica
6.2. Incompatibilities
No major incompatibilities although certain non steroidal anti-inflammatory agents are known to antagonise the action of frusemide.
6.3. Shelf life
5 years.
6.4. Special precautions for storage
Will be stored in a dry place below 25°C , protected from light .
6.5. Nature and contents of container
Packs of 28, 56, 100, 250, 500, 1000 packed in plastic securitainer with polypropylene lids containing frusemide tablets (material of the container complies to EEC directives for plastic in contact with drugs and food stuff). Blister packs of 0.25mm thick PVC and Aluminium foil thickness of 20 microns.
6.6. Instruction for use and handling
None
7 MARKETING AUTHORISATION HOLDER
Pharmvit Limited
177 Bilton Road, Perivale
Greenford,
Middlesex UB6 7HQ
8 MARKETING AUTHORISATION NUMBER(S)
PL 04556/0003
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
17/03/2004
10 DATE OF REVISION OF THE TEXT
06/12/2010