Furosemide 20mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Furosemide 20mg Tablets BP
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 20mg of Furosemide For excipients see 6.1
3. PHARMACEUTICAL FORM
Tablet
Appearance: White, circular, flat bevelled edge tablet with a breakline on one side.
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
Method of administration: Oral - the tablets should be swallowed with water.
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 1,500mg in 24 hours. In exceptional cases up to 2,000mg 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.
4.3 Contraindications
Furosemide is contraindicated in the following circumstances
• Hypersensitivity to furosemide, any of its 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, hypovolaemia), dehydration and/or hypotension (see section 4.4)
• Concomitant potassium supplements or potassium sparing diuretics (see section 4.5)
• Pre-coma/coma associated with hepatic cirrhosis or encephalopathy
• Addison's disease
• Porphyria
• Digitalis intoxication (see also section 4.5)
• Breast-feeding women (see section 4.6)
4.4 Special warnings and precautions for use
Hypotension and/or hypovolaemia (see also section 4.3)
These and any acid-base disturbances should be corrected before furosemide is started
Dose titration/adjustment (see section 4.2)
• Patients with hypoproteinaemia (such as that associated with the
nephotic syndrome) require careful dose titration (reduced furosemide effect: increased risk of ototoxicity)
• In moderate liver congestion dosage adjustment may be needed
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
• Difficulty with micturition/potential obstruction in the urinary tract
including prostatic hypertrophy (increased risk of acute retention).
• 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.
• Gout (increased risk of hyperuricaemia)
• Patients at risk of pronounced falls in blood pressure
• Symptomatic hypotension leading to dizziness, fainting or loss of
consciousness can occur in patients treated with furosemide, particularly in the elderly, patients on other medications which can cause hypotension and patients with other medical conditions that are risks for hypotension.
Clinical monitoring requirements (see also section 4.8):
Regular monitoring for
• Blood dyscrasias. If these occur, stop furosemide immediately
• Liver damage
• Idiosyncratic reactions
In premature infants there is a risk of development of nephrocalcinosis/nephrolithiasis. Renal function must be monitored and renal ultrasonography performed.
Laboratory monitoring requirements:
• Frequent BUN in first few months of treatment, periodically thereafter
• Serum electrolytes with replacement as appropriate
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
Discontinue furosemide if bone marrow suppression occurs.
This product contains lactose. Patients with rare herditary problems of 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
Antihypertensives - enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors can result in marked falls in blood pressure. Furosemide should be stopped or the dose reduced before starting an ACE inhibitor.
There is a risk of a first-dose effect with post-synaptic alphablockers eg prazosin. Furosemide may interact with ACE inhibitors causing impaired renal function.
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.
Anti-arrhythmics (including amiodarone, disopyramide, flecanaide and sotalol) - risk of cardiac toxicity (because of furosemide-induced hypokalaemia). The effects of lidocaine, tocainide or mexiletine may be antagonised by furosemide.
Drugs associated with QT prolongation - cardiac toxicity may be increased by furosemide-induced hypokalaemia and/or hypomagnesaemia.
Cardiac glycosides - hypokalaemia and electrolyte disturbances (including magnesium) increases the risk of cardiac toxicity.
Vasodilators - enhanced hypotensive effect with moxisylyte (thymoxamine) or hydralazine.
Renin inhibitors - aliskiren reduces plasma concentrations of furosemide.
Nitrates - enhanced hypotensive effect.
Lithium - Furosemide reduces lithium excretion with increased plasma lithium concentrations (risk of toxicity). Avoid concomitant administration unless plasma levels are monitored.
Chelating agents - sucralfate may decrease the gastro-intestinal absorption of furosemide - the 2 drugs should be taken at least 2 hours apart.
Lipid regulating drugs — Bile acid sequestrants (eg colestyramine: colestipol) -reduced absorption of Furosemide - administer 2 to 3 hours apart.
NSAIDs - increased risk of nephrotoxicity (especially if there is hypovolaemia). Indometacin and ketorolac may antagonise the effects of furosemide. . In patients with dehydration or hypovolaemia, NSAIDs may cause acute renal insufficiency.
Salicylates - effects may be potentiated by furosemide.
Antibiotics - increased risk of ototoxicity with aminoglycosides, polymixins or vancomycin. Increased risk of nephrotoxicity with aminoglycosides or cefaloridine. Furosemide can decrease vancomycin serum levels after cardiac surgery.
Antidepressants - enhanced hypotensive effect with MAOIs. Increased risk of postural hypotension with TCAs (tricyclic antidepressants). Possible increased risk of hypokalaemia with reboxetine.
Antidiabetics - hypoglycaemic effects antagonised by furosemide.
Insulin - requirements may be increased (see section 4.4).
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 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 antagonised (sodium retention) and increased risk of hypokalaemia.
Cytotoxics - increased risk of nephrotoxicity and ototoxicity with platinum compounds.
Other diuretics - profound diuresis possible when furosemide given with metolazone. Increased risk of hypokalaemia with thiazides.
Dopaminergics - enhanced hypotensive effect with levodopa.
Immunomodulators - enhanced hypotensive effect with aldesleukin.
Muscle relaxants - enhanced hypotensive effect with baclofen or tizanidine (see also Anaesthetic agents below - curare).
Oestrogens and progestogens - diuretic effect antagonized.
Prostaglandins - enhanced hypotensive effect with alprostadil.
Sympathomimetics - increased risk of hypokalaemia with high doses of beta2 sympathomimetics (such as bambuterol, femoterol, salbutamol, salmeterol and terbutaline).
Theophylline - enhanced hypotensive effect.
Probenecid - reduced renal clearance of probenecid and decreased diuretic effect.
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.
Liquorice - excess intake may increase the risk of hypokalaemia.
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
Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000); Frequency not known (cannot be estimated from the available data).
|
Blood and lymphatic |
Uncommon: |
aplastic anaemia |
|
system disorders |
Rare: |
Bone marrow depression (necessitates withdrawal of treatment), eosinophilia, leucopenia. |
|
Very rare: |
Haemolytic anaemia, agranulocytosis, thrombocytopenia. |
|
Metabolism and nutrition disorders |
Very common: |
dehydration, hyponatraemia, hypochloremic metabolic alkalosis, hypocalcaemia, hypomagnesemia (incidences of the last three are reduced by triamterene). |
|
Common: |
Hypovolaemia, hypochloraemia | |
|
Uncommon: |
impaired glucose tolerance (by hypokalaemia), hyperuricaemia, gout, reduction of serum HDL-cholesterol, elevation of serum LDL-cholesterol, elevation of serum triglycerides, hyperglycaemia | |
|
Very rare: |
tetany | |
|
Frequency not known: |
Aggravated pre-existing metabolic alkalosis (in decompensated cirrhosis of the liver), fluid and electrolyte disturbances. | |
|
Psychiatric disorder |
Rare: |
Psychiatric disorder NOS |
|
Nervous system disorders |
Rare: |
Paraesthesia, confusion, headache, dizziness. |
|
Frequency not known |
Dizziness, fainting and loss of consciousness (caused by symptomatic hypotension). | |
|
Eye disorders |
Uncommon: |
visual disturbance, blurred vision, yellow vision, photosensitivity |
|
Ear and labyrinth disorders |
Rare: |
tinnitus and reversible or irreversible loss of hearing (although usually transitory, particularly in patients with renal failure, hypoproteinaemia (e.g. in nephritic syndrome) |
|
Uncommon |
deafness (sometimes irreversible) | |
|
Cardiac disorders |
Uncommon: |
Orthostatic intolerance, cardiac arrhythmias. |
|
Vascular disorders |
Very common: |
decreased 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). | ||
|
Rare: |
vasculitis, thrombosis, shock | |
|
Gastrointestinal disorders |
Uncommon: |
dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhoea, constipation |
|
Rare: |
Acute pancreatitis (in long-term diuretic treatment, including furosemide). | |
|
Hepatobiliary disorders |
Rare: |
Pure intrahepatic cholestasis (jaundice), hepatic function abnormal. |
|
Uncommon |
Liver dysfunction | |
|
Skin and subcutaneous tissue disorders |
Rare: |
Rash, pruritus, photosensitivity, toxic epidermal necrolysis. |
|
Frequency not known: |
urticaria, erythema multiforme, purpura, exfoliative dermatitis, itching, allergic reactions, such as skin rashes, various forms of dermatitis including urticaria, bullous lesions and acute generalised exanthematous pustulosis (AGEP). When these occur treatment should be withdrawn. | |
|
Musculoskeletal and connective tissue disorders |
Uncommon: |
Muscle cramps, muscle weakness. |
|
Renal and urinary disorders |
Uncommon: |
reduced diuresis, urinary incontinence, urinary obstruction (in patients with hyperplasia of the prostate, bladder inability to empty, urethral stricture unspecified) |
|
Rare: |
nephrocalcinosis (in pre-term infants treated with Furosemide), interstitial nephritis, acute renal failure | |
|
Congenital, familial and genetic disorders |
Rare: |
patent ductus arteriosus |
|
General disorders and administration site conditions |
Uncommon: |
Fatigue |
|
Rare: |
malaise, fever, severe anaphylactoid or anaphylactic reactions (e.g. with shock). | |
|
Investigations |
Common: |
creatinine increased, blood |
|
urea increased | |
|
Rare: |
Transaminases increased, blood |
Reporting of suspected adverse reactions
Reporting 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, website www.mhra.gov.uk/yellowcard.
4.9 Overdose
In cases of overdosage there is a danger of dehydration and electrolyte depletion and hypotension due to excessive diuresis. Treatment should be aimed at fluid replacement and correction of electrolyte imbalance. The drug should be discontinued and electrolyte and water replacement instituted immediately; adjustment should be on the basis of careful monitoring.
Gastric lavage may be useful if ingestion is recent.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC code: 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. The principle renal action of furosemide is to inhibit active chloride transport in the thick ascending limb. 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 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 a weak carboxylic acid which exists mainly in the dissociated form in the gastrointestinal tract.
Furosemide is rapidly but incompletely absorbed (60-70%) on oral administration and its effect is largely over within 4
hours. The optimal absorption site is the upper duodenum at pH 5.0. Regardless of route of administration 69-97% of activity from a radio-labelled dose is excreted in the first 4 hours after the drug is given. Furosemide is bound to plasma albumin and little biotransformation takes place. Furosemide is mainly eliminated via the kidneys (80-90%); a small fraction of the dose undergoes biliary elimination and 10-15% of the activity can be recovered from the faeces.
In renal/ hepatic impairment
Where liver disease is present, biliary elimination is reduced up to 50%. Renal impairment has little effect on the elimination rate of furosemide, but less than 20% residual renal function increases the elimination time.
The elderly
The elimination of furosemide is delayed in the elderly where a certain degree of renal impairment is present.
New born
A sustained diuretic effect is seen in the newborn, possibly due to immature tubular function.
5.3. Preclinical Safety Data
Not relevant.
6. PHARMACEUTICAL PARTICULARS
6.1. List of Excipients
Maize starch Lactose monohydrate Sodium starch glycollate Magnesium stearate Maize starch paste 15% w/w
6.2. Incompatibilities
None known.
6.3.
Shelf Life
1. Polypropylene tubes with low density polyethylene caps: 3 years.
2. Blister: 2 years.
6.4. Special Precautions for Storage
1. Polypropylene tubes: Do not store above 25°C. Store in the original container. Keep the container tightly closed.
2. Blister: Do not store above 25°C. Store in the original packaging. Keep in the outer carton.
6.5. Nature and Contents of Container
1. Polypropylene tubes fitted with low density polyethylene caps containing 28 or 250 tablets.
2. Blister (250pm white opaque PVC and 20pm hard temper aluminium foil, in a carton) containing 28 tablets.
6.6. Instruction for Use/Handling Not applicable.
7 MARKETING AUTHORISATION HOLDER
RelonChem Limited 27 Old Gloucester Road London WC1 3XX United Kingdom
8. MARKETING AUTHORISATION NUMBER
PL 20395/0030
9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
16 March 2004
10
DATE OF REVISION OF THE TEXT
11/03/2016