Furosemide 40mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Furosemide 40mg Tablets BP.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each Tablet contains 40mg Furosemide.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet.
Appearance
A white, circular, flat bevelled edge tablet marked with LPC on one side.
F40
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 40mg. This may require adjustment until the effective dose is achieved. In mild cases 20mg daily or 40mg on alternate days may be sufficient, whereas in cases of resistant oedema daily doses of 80mg and above may be used.
In patients with chronic renal insufficiency, an initial daily dose of 250mg is employed. If a satisfactory diuresis is not produced then the dose may be increased in steps of 250mg 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 1-3mg/kg body weight daily, up to a maximum total dose of 40mg per day.
Elderly: The usual adult dose, but caution is advised as furosemide is excreted more slowly in the elderly.
Method of administration: Oral - the tablets should be swallowed with water.
4.3 Contraindications
Furosemide is contra-indicated in patients with hypovolaemia or dehydration, anuria or renal failure with anuria not responding to furosemide, renal failure as a result of poisoning by nephrotoxic or hepatotoxic agents or renal failure associated with hepatic coma, severe hypokalaemia, severe hyponatraemia, precomatose and comatose states associated with hepatic encephalopathy.
Furosemide is also contraindicated in patients with electrolyte deficiency, digitalis intoxication, and porphyria.
Furosemide is contraindicated in breast-feeding women.
Hypersensitivity to Furosemide or any of the excipients of Furosemide tablets (see section 6.1). Patients allergic to sulphonamides may show crosssensitivity to Furosemide.
4.4 Special warnings and precautions for use
Where indicated, steps should be taken to correct hypotension or hypovolaemia before commencing therapy. Regular monitoring of fluid and electrolyte balance is recommended.
Use with caution in patients with impaired hepatic or renal function, diabetes mellitus or adrenal disease.
Use with care in elderly patients or those with prostatic hypertrophy or impairment of micturition.
Latent diabetes may become manifest or the insulin requirement of diabetic patient may increase.
Hypotension may occur if ACE inhibitors are added to furosemide therapy. The dose of furosemide should be reduced or the drug stopped before initiating the ACE inhibitor.
Use with caution in patients with a history of gout. Discontinue furosemide if bone marrow depression occurs.
Patients with hyponatraemia 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 ultrasonagrapy performed).
Caution should be observed 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.
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.
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.
If Furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patient ductus arteriosus.
4.5 Interaction with other medicinal products and other forms of interaction
The dosage of concurrently administered cardiac glycosides or antihypertensive agents may require adjustment. Some electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia) may increase the toxicity of certain other drugs (e.g. digitalis preparations and drugs including QT interval prolongation syndrome). Within this context, corticosteroid, carbenoxolone, liquorice, B2 sympathomimetic in large amounts, prolonged use of laxatives, reboxetine and amphotericine may increase the risk of developing hypokalaemia.
A marked fall in blood pressure and deterioration in renal function may be seen when ACE inhibitors are added to Furosemide therapy. The dose of Furosemide should be reduced at least three days, or the drug stopped, before initiating the ACE inhibitor or increasing the dose of an ACE inhibitor.
The hypotensive effect of Furosemide could be enhanced when it is concomitantly given with antihypertensive medications, during central anaesthesia, anxiolytic and hypnotics, MAOIs, and vasodilators.
Furosemide, if prescribed together with alpha-blockers, increases the risk of first-dose hypotension with post-synaptic alpha-blockers such as prazosin.
Furosemide may potentiate the ototoxicity of aminoglycosides and other ototoxic drugs. Since this may lead to irreversible damages, these drugs must only be used with Furosemide if there are compelling medical reasons.
The toxic effects of nephrotoxic antibiotics may be increased by concomitant administration of potent diuretics such as Furosemide.
Impairment of renal function may develop in patients receiving treatment with Furosemide and high doses of certain cephalosporins.
Certain non-steroidal anti-inflammatory agents (e.g. Indomethacin, acetylsalicylic acid) may attenuate the action of Furosemide and may cause acute renal failure in cases of pre-existing hypovolaemia or dehydration. Salicylate toxicity may be increased by Furosemide. Furosemide may sometimes attenuate the effects of other drugs (e.g. the effects of anti-diabetics and pressor amines) and sometimes potentiate them (e.g. the effects of salicylate, theophylline and curare-type muscle relaxant
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 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.
Concomitant administration of carbamazipine or aminoglutethimidine may increase the risk of hyponatraemia.
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 drugs. In case of high-dose treatment (in particular, of both Furosemide and the other drugs), this may lead to increased serum levels and an increased risk of adverse effects due to Furosemide or the concomitant medication.
Corticosteroid administration concurrently may cause sodium retention.
Attenuation of the effect of Furosemide may occur following concurrent administration of phenytoin.
In common with other diuretics, serum lithium levels may be increased when lithium is given concomitantly with Furosemide, resulting in increased lithium toxicity. Therefore, it is recommended that lithium levels are carefully monitored and where necessary the lithium dosage is adjusted in patients receiving this combination.
4.6 Pregnancy and lactation
Results of animal work, in general, show no hazardous effect of furosemide in pregnancy. There is clinical evidence of safety of the drug in the third trimester of human pregnancy; however, furosemide crosses the placental barrier. It must not be given during pregnancy unless there are compelling medical reasons. Treatment during pregnancy requires monitoring of foetal growth.
Furosemide passes into breast milk and may inhibit lactation. Women must not breast-feed if they are treated with furosemide.
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
Listed below are side effects, which have been associated with the administration of Furosemide.
Blood and Lymphatic System disorders
Thrombocytopenia may occasionally occurs.
Leucopenia , eosinophilia, and bone marrow depression are rarely reported. The development of bone marrow depression necessitates withdrawal of treatment.
In isolated cases, agranulocytosis, aplastic anaemia or haemolytic anaemia may develop.
Cardio-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, weakness, disorders of vision, dry mouth, Orthostatic intolerance.
Ear and Labyrinth 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.
Endocrine disorders
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.
Hepatobiliary disorders
In isolated cases, intrahepatic cholestasis, an increase in liver transaminases.
Immune System disorders
Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely. Interstitial nephritis and vasculitis are very rarely reported.
Gastrointestinal disorders
Side effects of a minor nature such as nausea, malaise or gastric upset (vomiting or diarrhoea) may occur but are not usually severe enough to necessitate withdrawal of treatment.
Pancreatitis is very rarely reported
Metabolism and Nutritional disorders
As with other diuretics, electrolytes and water balance may be disturbed as a result of diuresis after prolonged therapy.
The administration of furosemide could lead to hyponatraemia, hypokalaemia, hypomagnesaemia, and hypochloraemic alkalosis.
Serum calcium levels may be reduced; in very rare cases tetany has been observed. Nephrocalcinosis / Nephrolithiasis has been reported in premature infants.
Warning signs of electrolyte disturbances include increased thirst, headache, hypotension, confusion, muscle cramps, tetany, muscle weakness, disorders of cardiac rhythm and gastrointestinal symptoms.
Serum levels of uric acid may increase and attacks of gout may occur.
As with other diuretics, treatment with furosemide may lead to transitory increases in blood creatinine and urea levels.
Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated by furosemide treatment.
Serum cholesterol and triglyceride levels may rise during furosemide treatment. During long term therapy they will usually return to normal within six months.
Serum calcium levels may be reduced; in very rare cases tetany has been observed. Nephrocalcinosis / Nephrolithiasis has been reported in premature infants.
Musculoskeletal, Connective tissue, and Bone disorders
Muscle spasm has been reported.
Skin and Subcutaneous tissue disorders
The incidence of allergic reactions, such as skin rashes, photosensitivity, vasculitis, fever, interstitial nephritis or shock is very low, but when these occur treatment should be withdrawn. Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, erythema multiforme, exfoliative dermatitis, purpura.
Paraesthesia has been reported.
4.9 Overdose
In cases of overdose 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
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 re-absorption. It increases renal blood flow without increasing the filtration rate. Such a change in renal haemodynamics reduces fluid and electrolyte re-absorption 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 a 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 in sodium excretion. Unlike the thiazides, high ceiling diuretics do not increase calcium re-absorption in the distal tubule. The calciuric action of these agents is the basis for their use in symptomatic hypercalcaemia.
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
Not relevant
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate, Magnesium stearate, Sodium starch glycollate Maize starch.
Starch paste 15%
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Tablet container: 5 Years Blister: 2 Years
6.4 Special precautions for storage
o
Do not store above 25 C. Store in the original container. Keep the container tightly closed - Tablet containers.
o
Do not store above 25 C. Store in the original package - Blister packs
6.5 Nature and contents of container
1. Tablet container and cap (polypropylene container with low density polyethylene cap)
Pack sizes: 28, 56, 100, 250, 500, 504, 1000 and 1008 tablets.
2. Blister (250 pm white opaque PVC and 20 pm hard temper aluminium foil). Pack sizes: 28, 56 and 1008 tablets.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Founts (UK) Pharmacare Ltd First Floor,
2 Victoria Road,
Harpenden,
Hertfordshire,
A15 4EA,
United Kingdom
MARKETING AUTHORISATION NUMBER(S)
PL 39484/0022
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/07/2011
10 DATE OF REVISION OF THE TEXT
15/07/2011