Furosemide 40mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Furosemide 40mg Tablets.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Furosemide BP 40.0mg.
3. PHARMACEUTICAL FORM
Tablet.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
The treatment of fluid retention associated with heart failure, including left ventricular failure, cirrhosis of the liver and renal disease including nephrotic syndrome.
The treatment of mild to moderate hypertension when brisk diuretic response is required. Alone or in combination with other antihypertensive agents in the treatment of more severe cases.
4.2. Posology and method of administration
For oral administration.
Adults
The initial adult dose is 40mg daily, reduced to 20mg daily or 40mg on alternate days. In some patients daily doses of 80mg or higher (given in divided doses) may be required.
Children
The usual dose is 1-3 mg/kg body weight daily up to a maximum dose of 40mg/day.
Elderly
Caution is advised as furosemide is excreted more slowly in the elderly. Treatment should be started with 20mg and titrated upwards as required.
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
Furosemide should be discontinued before a glucose tolerance test.
Furosemide should be used with particular caution in elderly patients or those with potential obstruction of the urinary tract or disorders rendering electrolyte balance precarious.
Regular monitoring of fluids and electrolyte balance is recommended. Where indicated, steps should be taken to correct hypotension or hypovolaemia before commencing therapy. This may require temporary discontinuation of Furosemide. Regular monitoring of serum sodium, potassium, creatinine and glucose is generally recommended during therapy; particularly close monitoring is required in patients at high risk of developing electrolyte imbalances or in case of significant additional fluid loss. Of note, the risk of electrolyte disturbances can be increased even in mild renal failure.
Frequent checks of the serum potassium level are necessary in patients with impaired renal function and a creatinine clearance below 60ml/min per 1.73m2 body surface area as well as in cases where Furosemide is taken in combination with certain other drugs which may lead to an increase in potassium levels.
Particularly careful monitoring is necessary in the following cases :
- Latent diabetes may become manifest or the insulin requirements of diabetic patients may increase.
- Hepatic failure and alcoholic cirrhosis particularly predispose to hypokalaemia and hypomagnesaemia. (Refer to section 4.8 for details of electrolyte and metabolic abnormalities).
- Use with caution in patients with a history of gout. Furosemide may predispose the patient to the development of hyperuricaemia. (Refer to Section 4.8)
- Patients with hypoproteinaemia, e.g. associated with nephrotoxic syndrome (the effect of furosemide may be weakened and its ototoxicity potentiated). Cautious dose titrated is required.
Use with caution in patients with impaired hepatic, cardiac or renal function, diabetes mellitus or adrenal disease and elderly patients.
In patients who are at high risk for radiocontrast nephropathy, furosemide is not recommended to be used for diuresis as part of the preventative measures against radiocontrast-induced nephropathy.
Acute diuresis may cause urinary retention in patients with urinary outflow obstruction (such as prostatic hyperplasia/ hypertrophy or impairment of micturition). Urinary output must be monitored in these patients.
Co-administration with nonsteriodal anti-inflammatory analgesics (NSAIDs) should be avoided wherever possible. Where this is not possible, particularly careful monitoring is required to ensure that the diuretic effect is not attenuated (Refer to section 4.5).
Use with caution in patients with hypotension, liver failure, prostate enlargement.
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.
Patients with rare hereditary problems of glucose galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interactions with other Medicinal Products and other Forms of Interaction
Antihypertensives:
Enhanced hypotensive effect possible with all types. Concurrent use with ACE inhibitors or Angiotensin II receptor antagonists can result in marked falls in blood pressure, furosemide should be stopped or the dose reduced before starting an ACE-inhibitor or Angiotensin II receptor antagonists.
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.
In risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone. No consistent pattern for cause of death was observed but caution should be exercised and the risks and benefits of this combination considered prior to the decision to use.
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.
Cardiac glycosides:
Hypokalaemia and electrolyte disturbances (including hypomagnesia) increase the risk of cardiac toxicity.
Drugs that prolong Q-T interval:
Increased risk of toxicity with furosemide-induced electrolyte disturbances
Vasodilators:
Enhanced hypotensive effect with moxisylyte (thymoxamine) or hydralazine Other diuretics:
Profound diuresis possible when furosemide given with metolazone. Increased risk of hypokalaemia with thiazides. Contraindicated with potassium sparing diuretics (eg Amiloride spironolactone) - increased risk of hyperkalaemia
Renin inhibitors:
Aliskiren reduces plasma concentrations of frurosemide
Nitrates:
Enhanced hypotensive effect Lithium:
Furosemide reduces lithium excretion with increased plasma lithium concentrations (risk of cardio- and/or neuro-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
NSAIDs:
Increased risk of nephrotoxicity. Indometacin and ketorolac may antagonise the effects of furosemide
Salicylates:
Effects may be potentiated by furosemide. Salycylic toxicity may be increased by furosemide
Antibiotics:
Increased risk of ototoxicity with aminoglycosides, polymixins or vancomycin - only use concurrently if compelling reasons. Increased risk of nephrotoxicity with aminoglycosides or cefaloridine. Furosemide can decrease vancomycin serum levels after cardiac surgery. Increased risk of hyponatraemia with trimethoprim
Antidepressants:
Enhanced hypotensive effect with MAOIs. Increased risk of postural hypotension with TCAs (tricyclic antidepressants). Increased risk of hypokalaemia with reboxetine
Antidiabetics:
Hypoglycaemic effects antagonised by furosemide
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 and nephrotoxicity with amphoterecin
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 anatgonised (sodium retention) and increased risk of hypokalaemia Glychyrrizin (contained in liquorice):
May increase the risk of developing hypokalaemia.
Cytotoxics:
Increased risk of nephrotoxicity and ototoxicity with platinum compounds/cisplatin
Anti-metabolites:
Effects of furosemide may be reduced by methotrexate and furosemide may reduce renal clearance of methotrexate
Potassium salts:
Contraindicated - increased risk of hyperkalaemia
Dopaminergics:
Enhanced hypotensive effect with levodopa.
Immunomodulators:
Enhanced hypotensive effect with aldesleukin. Increased risk of hyperkalaemia with ciclosprin and tacrolimus. Increased risk of gouty arthritis with ciclosporin
Muscle relaxants:
Enhanced hypotensive effect with baclofen or tizanidine. Increased effect of curarelike muscle relaxants
Oestrogens:
Diuretic effect antagonised
Progestogens:
Increased risk of hyperkalaemia
Prostaglandins:
Enhanced hypotensive effect with alprostadil
Sympathomimetics:
Increased risk of hypokalaemia with high doses of beta2 sympathomimetics
Theophylline:
Enhanced hypotensive effect Probenecid:
Effects of frusemide may be reduced by probenecid and frusemide may reduce renal clearance of probenecid.
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
4.6. Pregnancy and lactation
Pregnancy:
Furosemide crosses the placental barrier and should not be given during pregnancy unless there are compelling medical reasons. It should only be used for the pathological causes of oedema which are not directly or indirectly linked to the pregnancy. The treatment with diuretics of oedema and hypertension caused by pregnancy is undesirable because placental perfusion can be reduced, so, if used, monitoring of fetal growth is required. However, furosemide has been given after the first trimester of pregnancy for oedema, hypertension and toxaemia of pregnancy without causing fetal or newborn adverse effects.
Lactation:
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
Undesirable effects can occur with the following frequencies: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1,000, < 1/100), rare (> 1/10,000, < 1,000) and very rare (< 1/10,000, including isolated reports).
Blood and lymphatic system disorders:
Uncommon:
thrombocytopenia
Rare:
Eosinophilia
Leukopenia
Bone marrow depression (necessitates withdrawal of treatment). The haemopoietic status should be therefore be regularly monitored.
Very Rare:
• aplastic anaemia or haemolytic anaemia
• agranulocytosis
Endocrine disorder
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. Insulin requirements of diabetic patients may increase.
Metabolism and nutrition disorders
As with other diuretics, electrolytes and water balance may be disturbed as a result of diuresis after prolonged therapy. Furosemide leads to increased excretion of sodium and chloride and consequently increase excretion of water. In addition, excretion of other electrolytes (in particular potassium, calcium and magnesium) is increased.
Metabolic acidosis can also occur. The risk of this abnormality increases at higher dosages and is influenced by the underlying disorder (e.g. cirrhosis of the liver, heart failure), concomitant medication (see section 4.5) and diet.
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,
Symptoms of electrolyte imbalance depend on the type of disturbance:
Sodium deficiency can occur; this can manifest itself in the form of confusion, muscle cramps, muscle weakness, loss of appetite, dizziness, drowsiness and vomiting.
Potassium deficiency manifests itself in neuromuscular symptoms (muscular weakness, paralysis), intestinal symptoms (vomiting, constipation, meterorism), renal symptoms (polyuria) or cardiac symptoms. Severe potassium depletion can result in paralytic ileus or confusion, which can result in coma.
Magnesium and calcium deficiency result very rarely in tetany and heart rhythm disturbances.
Serum calcium levels may be reduced; in very rare cases tetany has been observed.
Nephrocalcinosis/Nephrolithiasis has been reported in premature infants.
Serum cholesterol (reduction of serum HDL-cholesterol, elevation of serum LDL-cholesterol) and triglyceride levels may rise during furosemide treatment. During long term therapy they will usually return to normal within six months,
As with other diuretics, treatment with furosemide may lead to transitory increase in blood creatinine and urea levels. Serum levels of uric acid may increase and attacks of gout may occur.
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.
Nervous system disorders Rare:
paraesthesia hyperosmolar coma confusion
Eye disorders
Uncommon: visual disturbance
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 intravenons furosemide has been given too rapidly.
Cardiac disorders Uncommon: Cardiac arrhythmias
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. The diuretic effect of furosemide can result in hypovolaemia and dehydration, especially in the elderly. There is an increased risk of thrombosis.
Vascular Disorder:
Rare:
vasculitis
Gastrointestinal disorders
Uncommon: dry mouth, thirst, nausea, bowel motility disturbances, vomiting, diarrhea, constipation.
Rare:
acute pancreatitis
Gastro-intestinal disorders such as nausea, malaise or gastric upset (vomiting or diarrhoea) and constipation may occur but not usually severe enough to necessitate withdrawal of treatment.
Hepatobiliary disorders
In isolated cases, intrahepatic cholestasis, an increase in liver transaminases or acute pancreatitis may develop.
Hepatic encephalopathy in patients with hepatocellular insufficiency may occur (see Section 4.3).
Skin and subcutaneous tissue disorders Uncommon:
Photosensitivity
Rare:
Skin and mucous membrane reactions may occasionally occur, e.g. itching, urticaria, other rashes or bullous lesions, fever, hypersensitivity to light, exsudative erythema multiforme (Lyell's syndrome and Stevens-Johnson syndrome), bullous exanthema, exfoliative dermatitis, purpura.
Musculoskeletal and connective tissue disorders
Uncommon:
muscle cramps
muscle weakness
Renal and urinary disorders Uncommon:
serum creatinine and urea levels can be temporarily elevated during treatment with furosemide.
Rare:
interstitial nephritis, acute renal failure.
Increased urine production, urinary incontinence, can be caused or symptoms can be exacerbated in patients with urinary tract obstruction. Acute urine retention, possibly accompanied by complications, can occur for example in patients with bladder disorders, prostatic hyperplasia or narrowing of the urethra.
Pregnancy, puerperium and perinatal conditions
In premature infants with respiratory distress syndrome, administration of Furosemide Tablets in the initial weeks after birth entails an increased risk of a persistent patent ductus arteriosus.
In premature infants, furosemide can be precipitated as nephrocalcinosis/kidney stones.
Rare complications may include minor psychiatric disturbances.
Congenital, familial and genetic disorders
If furosemide is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus. The product is contraindicated in children and adolescents under 18 years of age.
General disorders and administration site conditions
Uncommon: Fatigue
Rare:
Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely.
fever
Malaise
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 correction of electrolyte imbalance. Gastric lavage may be useful if ingestion is recent.
5.1 Pharmacodynamic properties
ATC code: CO3C A01
The evidence from many experimental studies suggests that furosemide acts along the entire nephron with the exception of the distal exchange site. The main effect is on the ascending limb of the loop of Henley with a complex effect on renal circulation. Blood-flow is diverted from the juxta-medullary region to the outer cortex.
The principle renal action of furosemide is to inhibit active chloride transport in the thick ascending limb. Re-absorption of sodium chloride from the nephron is reduced and a hypotonic or isotonic urine produced.
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 applicable.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Lactose
Starch
Magnesium stearate Povidone
Sodium starch glycollate.
6.2. Incompatibilities
None known.
6.3. Shelf life
2 years.
6.4. Special precautions for storage
Store in a cool dry place protected from light below 25°C.
6.5. Nature and contents of container
Securitainers and/or tampertainers containing 100, 250, 500, or 1000 tablets. PVC/Al Blister containing 28 tablets.
6.6. Instruction for Use/Handling and Disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Mercury Pharma (Generics) Ltd Capital House, 85 King William Street,
London EC4N 7BL, UK
8. MARKETING AUTHORISATION NUMBER
PL 16201/0013
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
15/11/2007
10 DATE OF REVISION OF THE TEXT
17/01/2014