Data Sheet
LASIX® & LASIX HIGH DOSE
Frusemide (furosemide)
NAME OF THE MEDICINE
Non-proprietary Name
Frusemide (furosemide)
Chemical Structure
CAS Number
54-31-9
DESCRIPTION
Lasix is an anthranilic acid derivative. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Frusemide is a white to off-white odourless crystalline powder. It is practically insoluble in water, sparingly soluble in alcohol, freely soluble in dilute alkali solutions and insoluble in dilute acids.
Lasix Oral Solution contains 10 mg/mL frusemide. Inactive ingredients include sorbitol, glycerol, sodium hydroxide, methyl hydroxybenzoate, potassium sorbate, polysorbate 80, butylated hydroxytoluene, butylated hydroxyanisole, ethanol, tetrarome orange 987431, quinoline yellow, purified water.
Lasix High Dose injection contains 250 mg/25 mL frusemide in water for injection (without solubiliser, pH about 9): Inactive ingredients include mannitol and sodium hydroxide. Contains 0.03 mmol/mL of sodium.
PHARMACOLOGY
Site and Mode of Action
Lasix is a potent diuretic. It inhibits sodium and chloride absorption in the ascending limb of Henle's loop and in both the proximal and distal tubules. The high degree of efficacy is due to this unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase or aldosterone.
Frusemide may promote diuresis in cases which have previously proved resistant to other diuretics.
Frusemide has no significant pharmacological effects other than on renal function.
Pharmacokinetics
Absorption
Frusemide is rapidly absorbed from the GIT. Absorption rates in healthy subjects have been reported from 60-69% and from 43-46% in patients with end stage renal failure.
The onset of diuresis following oral administration is within 1 hour. The peak effect occurs within the first or second hour. The duration of diuretic effect is 6 to 8 hours.
The onset of diuresis following intravenous administration is within 5 minutes and somewhat later after intramuscular administration. The peak effect occurs within the first half hour. The duration of diuretic effect is approximately 2 hours.
In fasted normal men, the mean bioavailability of frusemide from Lasix Tablets and Lasix Oral Solution is 64% and 60% respectively of that from an intravenous injection of the drug. Although frusemide is more rapidly absorbed from the oral solution (50 minutes) than from the tablet (87 minutes), peak plasma levels and area under the plasma concentration-time curves do not differ significantly. Peak plasma concentrations increase with increasing dose but times-to-peak do not differ among doses.
Distribution
Frusemide is extensively bound to plasma proteins, mainly to albumin. Plasma concentrations ranging from 1 to 400 μg/mL are 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.
Metabolism
Recent evidence suggests that frusemide glucuronide is the only, or at least the major, bio-transformation product of frusemide in man.
Excretion
In patients with normal renal function, approximately 80% of an intravenous or intramuscular dose is excreted in the urine within 24 hours. Urinary excretion is accomplished both by glomerular filtration and proximal tubular secretion, which accounts for roughly 66% of the ingested dose, the remainder being excreted in the faeces. A small fraction is metabolised by cleavage of the side chain.
Significantly more frusemide is excreted in urine following the IV injection than after the tablet or oral solution. There are no significant differences between the two oral formulations in the amount of unchanged drug excreted in urine.
Frusemide has a biphasic half life in the plasma with t1/2 ranging up to 100 minutes; t1/2 is prolonged by renal and hepatic insufficiency and in new born infants.
INDICATIONS
Oedema
Lasix is indicated in adults, infants and children for the treatment of oedema associated with congestive heart failure, cirrhosis of the liver and renal disease including the nephrotic syndrome. Lasix is particularly useful when an agent with greater diuretic potential than that of those commonly employed is desired. Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations.
Lasix Injection is also indicated as adjunctive therapy in acute pulmonary oedema and cerebral oedema where intense and rapid onset of diuresis is desired. If gastrointestinal absorption is impaired or oral medication is not practical for any reason, Lasix is indicated by the intravenous route. Parenteral use should be replaced with oral Lasix as soon as practical.
Hypertension
Oral Lasix may be used in adults for the treatment of hypertension alone or in combination with other antihypertensive agents. Hypertensive patients who cannot be adequately controlled with thiazides will probably also not be adequately controlled with Lasix alone.
CONTRAINDICATIONS
Known hypersensitivity to frusemide or sulfonamides or any of the inactive ingredients (see 'Description'). Patients allergic to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) may show cross-sensitivity to Lasix.
Lasix
Complete renal shutdown. If increasing azotaemia and oliguria occur during treatment of severe progressive renal disease, discontinue frusemide. Severe hypokalaemia, hyponatraemia, hypovolaemia or hypotension must be regarded as contraindications until serum electrolytes, fluid balance and blood pressure have been restored to normal levels.
In hepatic coma or precoma and conditions producing electrolyte depletion, frusemide therapy should not be instituted until the underlying conditions have been corrected or ameliorated.
Breast-feeding women.
Do not administer frusemide to newborns presenting jaundice or to infants with conditions which might induce hyperbilirubinaemia or kernicterus (e.g. Rhesus incompatibility, familial non-haemolytic jaundice etc.) because of frusemide's 'in vitro' potential to displace bilirubin from albumin.
Lasix High Dose
Complete renal shutdown; glomerular filtration rate below 5 mL/min or above 20 mL/min and renal failure due to poisoning with nephrotoxic or hepatotoxic substances; severe hyponatraemia, hypokalaemia, hypovolaemia or hypotension until electrolytes, volume and blood pressure have returned to normal.
Patients with normal renal function because there is a risk of severe fluid and electrolyte loss.
Hepatic cirrhosis; existing or impending hepatic coma. Jaundiced infants or infants with conditions which might induce hyperbilirubinaemia or kernicterus (e.g. Rhesus incompatibility, familial non-haemolytic jaundice etc).
Breast-feeding women.
Lasix 250 mg injection must not be used as a bolus injection. It must only be infused using volume or rate controlled infusion pumps to reduce the risk of accidental overdose.
PRECAUTIONS
Excessive diuresis may result in dehydration and reduction in blood volume with circulatory collapse and with the possibility of vascular thrombosis and embolism, particularly in elderly patients.
Excessive loss of potassium in patients receiving cardiac glycosides may precipitate digitalis toxicity.
In patients with hepatic cirrhosis and ascites, initiation of therapy with Lasix is best carried out in hospital. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma, therefore, strict observation is necessary during the period of diuresis.
Cases of reversible or irreversible tinnitus or hearing impairment have been reported. Usually, reports indicate that Lasix ototoxicity is associated with rapid injection or infusion, severe renal impairment, hypoproteinaemia, doses exceeding several times the usual recommended dose, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. In patients with hypoproteinaemia, e.g. associated with nephrotic syndrome, the effect of Lasix may be weakened and its ototoxicity potentiated. Cautious dose titration is required. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults with normal renal function, an infusion rate not exceeding 4 mg Lasix per minute must be used; for adults with impaired renal function [creatinine > 5 mg/dL], an infusion rate of no greater than 2.5 mg per minute must be used).
Caution should be exercised when administering curare or its derivatives to patients undergoing frusemide therapy. It is also advisable to discontinue frusemide for one week prior to any elective surgery.
Caution should be exercised and the risks and benefits of combining risperidone with Lasix or other potent diuretics should be considered prior to the decision to treat. In the risperidone placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with frusemide plus risperidone (7.3% ; mean age 89 years, range 75 to 97) compared to treatment with risperidone alone (3.1% ; mean age 84 years, range 70 to 96) or frusemide alone (4.1% ; mean age 80 years, range 67 to 90). Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low doses) was not associated with similar mortality findings. No pathophysiological mechanism has been identified to explain this finding and no consistent pattern for cause of death was observed. Nevertheless, caution is advised. Irrespective of treatment, dehydration was an overall risk factor for mortality and should, therefore, be carefully avoided in elderly patients with dementia.
Rigid sodium restriction is conducive to both hyponatraemia and hypokalaemia, thus strict restriction of sodium intake is not advisable in patients receiving frusemide.
Frusemide should be used with care, especially in the initial stages, in patients with impairment of micturition (e.g. prostatic hypertrophy). Urinary outflow must be secured. In patients with a partial obstruction of urinary outflow (e.g. in patients with bladder-emptying disorders, prostatic hyperplasia or narrowing of the urethra), increased production of urine may provoke or aggravate complaints. Thus, these patients require careful monitoring.
Particularly careful monitoring is required in patients with gout, patients with partial obstruction of urinary outflow, in patients at risk from hypotension (e.g. patients with coronary artery stenosis), in patients with latent or manifest diabetes mellitus, in patients with hepatorenal syndrome or in patients with hypoproteinaemia (e.g. associated with nephrotic syndrome). Dose titration, especially in this latter case, is required. In premature infants, there is the possible development of nephrocalcinosis/nephrolithiasis and therefore renal function must be monitored and renal ultrasonography performed. In premature infants frusemide administered during the first weeks of life may increase the risk of persistence of Botallo's duct.
As with any effective diuretic, electrolyte depletion may occur during therapy, especially in patients receiving higher doses and a restricted salt intake. All patients receiving Lasix therapy should be observed for signs of fluid or electrolyte imbalance; namely hyponatraemia, hypochloraemic alkalosis, and hypokalaemia. Periodic determinations of serum electrolytes to detect a possible imbalance should be performed at appropriate intervals, as well as creatinine, blood urea and CO2 content determinations. This is particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs of an imbalance, irrespective of cause include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, and gastrointestinal disturbances such as nausea and vomiting. Hypovolaemia or dehydration as well as any significant electrolyte and acid-base disturbances must be corrected. This may require temporary discontinuation of Lasix.
During long-term therapy, a high potassium diet is recommended. Potassium supplements may be required, especially when high doses are used for prolonged periods. Particular caution with potassium is necessary when the patient is on digitalis glycosides, potassium depleting steroids or in the case of infants and children. Potassium supplementation, diminution in dose, or discontinuation of frusemide therapy may be required.
Periodic checks on urine and blood glucose should be made in diabetics and even those suspected of latent diabetes when receiving Lasix. Increases in blood glucose and alterations in glucose tolerance tests with abnormalities of the fasting and 2-hour post prandial sugar have been observed, and rare cases of precipitation of diabetes mellitus have been reported.
Lasix may lower calcium levels, and rare cases of tetany have been reported. Accordingly, periodic serum calcium levels should be obtained.
In children, urge to defecate, complaints of abdominal pain and cramping have been reported after IV frusemide. An association of these symptoms with a low serum calcium and/or a low calcium/protein ratio is possible.
Reversible elevations of blood urea may be seen. These have been observed in association with dehydration, which should be avoided, particularly in patients with renal insufficiency.
Frusemide increases cholesterol and triglycerides short-term. It is not clear whether this effect persists long-term, however, the current evidence does not indicate this.
As with many other drugs, patients should be observed regularly for the possible occurrence of blood dyscrasias, liver damage, or other idiosyncratic reactions.
Renal calcifications (from barely visible on X-ray to staghorn) have occurred in some severely premature infants treated with intravenous Lasix for oedema due to patent ductus arteriosus and hyaline membrane disease. The concurrent use of chlorothiazides has been reported to decrease hypercalciuria and to dissolve some calculi.
The possibility exists of exacerbation or activation of systemic lupus erythematosus.
Asymptomatic hyperuricaemia can occur and rarely, gout may be precipitated.
The sorbitol present in the vehicle may cause diarrhoea (especially in children) when higher doses of Lasix Oral Solution are given.
When Lasix is administered parenterally, a maximum injection rate of 4 mg/minute should be used to minimise the risk of ototoxicity.
Intramuscular administration of Lasix must be limited to exceptional cases where neither oral nor intravenous administration are feasible. Intramuscular administration is not suitable for acute conditions such as pulmonary oedema.
Driving a Vehicle or Performing other Potentially Hazardous Tasks
Some adverse effects (e.g. an undesirable pronounced fall in blood pressure) may impair the patient's ability to concentrate and react and therefore constitute a risk in situations where these abilities are of special importance (e.g. operating a vehicle or machinery).
Use in Pregnancy
Category C
Lasix must not be given during pregnancy unless there are compelling medical reasons. Treatment during pregnancy requires monitoring of foetal growth.
Thiazides, related diuretics and loop diuretics enter the foetal circulation and may cause electrolyte disturbances. Neonatal thrombocytopaenia has been reported with thiazides and related diuretics. Loop diuretics, like frusemide and bumetanide, are probably also associated with this risk. During the latter part of pregnancy, products of this type should only be given on sound indications, and then in the lowest effective dose. In pregnancy, frusemide must only be used in patients with a marked reduction in glomerular filtration.
Use in Lactation
Frusemide passes into the breast milk and inhibits lactation. Women must not breast feed if being treated with frusemide.
Interactions with Food
Whether and to what extent the absorption of Lasix is affected by taking it with food seems to depend on the pharmaceutical formulation of Lasix. It is recommended that oral formulations of Lasix be taken on an empty stomach.
Interactions with other Medicines
Combinations that are not recommended
Lasix may increase the ototoxic and nephrotoxic potential of certain antibiotics (eg. aminoglycosides and certain cephalosporins (e.g cephaloridine), especially in the presence of impaired renal function, therefore the simultaneous administration of these drugs is not advisable.
Anticonvulsants may decrease the response to frusemide. In isolated cases intravenous administration of frusemide within 24 hours of taking chloral hydrate may lead to flushing, sweating attacks, restlessness, nausea, increase in blood pressure and tachycardia. Use of frusemide concomitantly with chloral hydrate is, therefore, not recommended.
Precautions for use
Lasix should not be used concomitantly with ethacrynic acid or cisplatin because of the possibility of ototoxicity. In addition, nephrotoxicity of cisplatin may be enhanced if Lasix 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.
Frusemide decreases the excretion of lithium salts and may cause increased serum lithium levels, resulting in increased risk of lithium toxicity, including increased risk of cardiotoxic and neurotoxic effects of lithium. Therefore, it is recommended that lithium levels are carefully monitored in patients receiving this combination.
Oral frusemide and sucralfate must not be taken within two hours of each other because sucralfate decreases the absorption of frusemide from the intestine and hence, reduces its effect.
The action of other antihypertensive drugs may be potentiated by Lasix, especially in combination with ACE inhibitors. The administration of ACE inhibitors to patients pretreated with frusemide may lead to a deterioration in renal function including renal failure, or may result in severe hypotension especially when an angiotensin converting enzyme inhibitor (ACE inhibitor) or angiotensin II receptor antagonist is given for the first time or for the first time in an increased dose. Consideration must be given to interrupting the administration of Lasix temporarily or at least reducing the dose of Lasix for 3 days before starting treatment with or increasing the dose of an ACE inhibitor or angiotensin II receptor antagonist.
Caution should be exercised and the risks and benefits of treating a patient on risperidone with Lasix or other potent diuretics should be considered prior to the decision to use. See PRECAUTIONS regarding increased mortality in elderly patients with dementia concomitantly receiving risperidone.
Take into account
The effects of digitalis preparations and drugs inducing QT interval prolongation syndrome may be potentiated by changes in electrolyte concentrations (e.g. hypokalaemia, hypomagnesaemia) due to frusemide. When a cardiac glycoside is administered concurrently, it should be remembered that potassium or magnesium deficiency increases the sensitivity of the myocardium to digitalis, and may increase the toxicity of drugs which induce QT interval prolongation syndrome. When a glucocorticoid is administered during diuretic treatment, the potassium-lowering effect of the steroid should be borne in mind (see PRECAUTIONS). Carbenoxolone, corticosteroids, prolonged use of laxatives or ingestion of liquorice in large amounts may also predispose a patient to hypokalaemia.
Patients receiving high doses of salicylates, as in rheumatic disease, in conjunction with Lasix may experience salicylate toxicity at lower doses because of competitive renal excretory sites.
Interactions between frusemide and neuromuscular blocking agents have been reported. These appear to be dependent on the dose of frusemide and the neuromuscular blocking agent involved. Low doses of frusemide (0.1-10 μg/kg) enhance the neuromuscular blockade of tubocurarine and succinylcholine. High doses (1-5mg/kg) of frusemide have a tendency to antagonise the skeletal muscle relaxing effect of tubocurarine but may potentiate the action of succinylcholine. The clinical relevance of these findings is uncertain.
The combination of frusemide and amphotericin may result in an excessive loss of potassium.
Lasix may decrease arterial responsiveness to noradrenaline. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.
If antihypertensive agents, diuretics or other drugs with blood-pressure lowering potential are given concomitantly with Lasix, a more pronounced fall in blood pressure must be anticipated.
Non-steroidal anti-inflammatory drugs including acetylsalicylic acid may reduce the natriuretic and antihypertensive effects of Lasix in some patients by inhibiting prostaglandin synthesis. In patients with dehydration or pre-existing hypovolaemia, non-steroidal anti-inflammatory drugs may cause acute renal failure. Salicylate toxicity may be increased by frusemide.
Phenytoin, methotrexate, probenecid and other drugs which, like frusemide, undergo significant renal tubular secretion may reduce the effect of frusemide. Conversely frusemide may decrease renal elimination of these drugs. In the case of high dose treatment (in particular of both frusemide and the other drugs), this may lead to an increased risk of adverse effects due to frusemide or the concomitant medication.
IV frusemide was shown to increase the steady state concentration of theophylline by 20% in a small number of asthmatic patients; hence it is appropriate to measure serum theophylline levels when both drugs are given together.
The effects of curare-type muscle relaxants or of theophylline may be increased.
It should be borne in mind that the effect of antidiabetics or of pressor amines (e.g. adrenaline, noradrenaline) may be attenuated by frusemide (see PRECAUTIONS).
Impairment of renal function may develop in patients receiving concurrent treatment with frusemide and high doses of certain cephalosporins. The harmful effects of nephrotoxic drugs on the kidney may be increased.
Concomitant use of cyclosporine A and frusemide is associated with increased risk of gouty arthritis secondary to frusemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion.
Patients who were at high risk for radiocontrast nephropathy treated with frusemide experienced a higher incidence of deterioration in renal function after receiving radiocontrast compared to high-risk patients who received only intravenous hydration prior to receiving radiocontrast.
ADVERSE EFFECTS
As with other diuretics, electrolytes and water balance may be disturbed during therapy with frusemide, especially in patients receiving high doses for a prolonged period.
Excessive diuresis may give rise, especially in elderly patients and children, to circulatory disturbances such as headache, dizziness, dry mouth or visual impairment, as symptoms of hypovolaemia. In extreme cases, hypovolaemia and dehydration may lead to hypotension, circulatory collapse and, in elderly patients in particular, thrombophilia. However, with individualised dosage, acute haemodynamic reactions are generally not to be expected, although diuresis sets in rapidly.
All saluretics may cause hypokalaemia, mainly in cases of low potassium diet, vomiting or chronic diarrhoea.
Factors such as underlying diseases (liver cirrhosis, cardiac failure), concomitant medication (see PRECAUTIONS - Interactions with other Medicines) or nutritional inadequacies (excessive restriction of salt intake), may lead to sodium or other electrolyte or fluid deficiencies which may produce a fall in orthostatic blood pressure, calf muscle spasms, anorexia, weakness, dizziness, drowsiness, apathy, vomiting and confusion.
Frusemide may lower the serum calcium level which may trigger a state of increased neuromuscular irritability. In very rare cases, tetany has been observed. In premature infants, calcium salts may be deposited in the renal tissue (nephrocalcinosis).
Hypomagnesaemia and, in rare cases, tetany or cardiac arrhythmias have been observed as a consequence of increased renal magnesium loss.
Treatment with Lasix may lead to transitory increases in blood creatinine and urea levels. Serum levels of uric acid may increase and attacks of gout may occur.
Pre-existing metabolic alkalosis (e.g. due to decompensated liver cirrhosis) may be aggravated during frusemide treatment.
Gastrointestinal / Digestive System
Reactions with normal doses are uncommon with Lasix. They include anorexia, oral and gastric irritation, nausea, vomiting, cramping, diarrhoea and constipation.
Hepatic System
In isolated cases, acute pancreatitis and increases in liver transaminases have been observed. Additionally, intrahepatic cholestasis and jaundice have been reported. Frusemide may increase the bile flow and distend the biliary tree which is already obstructed.
Central Nervous System
Reactions such as dizziness, vertigo, paraesthesia, headache and blurred vision occasionally accompany Lasix induced diuresis. Reversible hearing impairment and tinnitus and rarely, permanent tinnitus and impairment of hearing have been observed, especially in patients with markedly reduced renal function or hypoproteinaemia (e.g. in nephrotic syndrome). This occurs particularly when the recommended rate of injection or infusion of 4 mg per minute (normal renal function) or 2.5 mg per minute (impaired renal function) is exceeded, or in patients who are also receiving drugs known to be ototoxic.
Dermatologic System
Allergic reactions may occur in the form of dermatitis, including rash, urticaria and rare cases of exfoliative dermatitis, necrotising angitis, bullous eruptions, erythema multiforme and purpura and pruritus. Photosensitivity reactions have been reported.
Haematologic System
The following rare adverse reactions have been reported: eosinophilia, haemoconcentration, thrombophlebitis, haemolytic or aplastic anaemia, leukopaenia, thrombocytopaenia and agranulocytosis. Vasculitis may also occur.
Urinary System
Excessive diuresis and dehydration could cause transient elevation of creatinine and BUN and reduction of GFR. In elderly men with prostatic hypertrophy, acute urinary retention with overflow incontinence may occur. Symptoms of existing conditions of obstructed micturition, such as uretostenosis or hydronephrosis, may be triggered or aggravated by pronounced diuresis. Interstitial nephritis has also been reported with frusemide use.
Cardiovascular System
Orthostatic hypotension may occur and may be aggravated by alcohol, narcotics and barbiturates. Ischaemic complications have also been reported in elderly patients.
Other
Restlessness, hyperuricaemia, fever, a rise in serum cholesterol and triglyceride.
In patients with hepatocellular insufficiency, hepatic encephalopathy may occur.
Treatment with Lasix has occasionally caused reduced glucose tolerance and deterioration in cases of manifest diabetes, or made latent diabetes manifest.
Rarely, fever or paraesthesiae and occasionally photosensitivity may occur.
In premature infants, Lasix may precipitate nephrocalcinosis/nephrolithiasis. If Lasix is administered to premature infants during the first weeks of life, it may increase the risk of persistence of patent ductus arteriosus.
Following intramuscular injection, local reactions such as pain may occur.
Due to the possibility of side effects such as hypotension, patients' ability to drive or operate machinery may be impaired, especially at the commencement of therapy.
Anaphylactic shock is rare, but is acutely life-threatening if it does occur.
Whenever adverse reactions are moderate or severe, Lasix dose should be reduced or therapy withdrawn.
DOSAGE AND ADMINISTRATION
Lasix Oral Administration
Oedema:
Therapy should be individualised according to patient's response. This therapy should be titrated to gain maximal therapeutic response with the minimum dose possible to maintain that diuretic response.
Adults: The usual initial daily dose is 20 to 80 mg given as a single dose. If the diuretic response to a single dose of 20 to 80 mg is not satisfactory, increase this dose by increments of 20 to 40 mg, not sooner than 6 to 8 hours after the previous dose, until the desired diuretic effect is obtained. This individually determined dose should be given once or twice (e.g. at 8 am and 2 pm) daily. The dose of Lasix may be carefully titrated up to 400 mg/day (except in advanced renal failure) in those patients with severe clinical oedematous states. The mobilisation of oedema may be most efficiently and safely accomplished by giving Lasix on 2 to 4 consecutive days each week.
When doses exceeding 80 mg/day are given for prolonged periods, careful clinical laboratory observations are particularly advisable.
Infants and Children: The usual initial dose of oral Lasix for infants and children is 2mg/kg body weight given as a single dose. If the diuretic response is not satisfactory, the dose may be increased by 1 to 2 mg/kg no sooner than 6 to 8 hours after the previous dose. Doses of greater than 6 mg/kg body weight are not recommended.
For maintenance therapy in infants and children, the dose should be adjusted to the minimum effective level.
Hypertension:
Therapy should be individualised according to the patient's response. This therapy should be titrated to gain maximal therapeutic response with the minimum dose possible to maintain that therapeutic response.
Adults: The usual initial daily dose of Lasix for hypertension is 80 mg, usually divided into 40 mg twice a day. Dosage should then be adjusted according to response. If response is not satisfactory, add other antihypertensive agents.
Changes in blood pressure must be carefully monitored when Lasix is used with other antihypertensive drugs, especially during initial therapy.
To prevent an excessive drop in blood pressure, the dosage of other agents should be reduced by at least 50% when Lasix is added to the regimen. As the blood pressure falls under the potentiating effect of Lasix, a further reduction in dosage or even discontinuation of other antihypertensive drugs may be necessary.
Lasix High Dose Parenteral Administration
The high dosage preparations are intended exclusively for administration to patients with greatly reduced glomerular filtration rate (GFR less than 20 mL/min but greater than 5 mL/min). Normal doses of Lasix are usually adequate in patients with greatly reduced GFR if functional oliguria or anuria is observed. Thus, test a normal dose of Lasix first, before administering Lasix High Dose.
Before treatment of patients in shock is started, hypovolaemia and hypotension should be dealt with by suitable measures. Similarly, disturbed serum electrolytes and acid-base balance should first be corrected.
When treating patients with conditions likely to interfere with micturition, such as prostatic hypertrophy or disturbed consciousness, it is absolutely essential to ensure free urinary drainage. Because of the wide and unpredictable individual variations in responsiveness it is important to adjust dosage and route of administration to individual needs.
Once the desired rise in urinary output has begun, exact balance of water intake and water output must be maintained throughout the course of treatment so as to avoid hypovolaemia or hypotension. Careful electrolyte replacement is also necessary.
The dosage of high strength frusemide given below is for adults only. The dosage regimen for children has not yet been determined. The administration of large doses of frusemide in children has been associated with permanent deafness (see PRECAUTIONS).
Lasix High Dose - Intravenous Infusion
If a test dose of 40 to 80 mg Lasix, injected slowly IV over about 2 to 5 minutes, does not lead to increased diuresis within 30 minutes, infusion treatment with Lasix High Dose 250 mg is indicated.
Infusion fluid Lasix High Dose for IV use is a mildly buffered alkaline solution. Lasix High Dose can be added to 5% Dextrose in water Isotonic Saline or Lactated Ringer's Injection when mixed as directed and prepared immediately before use. Frusemide may precipitate in, and therefore is incompatible with, solutions in which the pH of the resulting mixture is less than 5.5. Frusemide should not be added into the tubing of a running infusion solution. Also, it should not be mixed with any other drugs in the infusion bottle.
Initial dose: The contents of one ampoule (250 mg/25 mL) are infused together with 250 mL of neutral to alkaline isotonic solution. The rate of infusion should not exceed 4 mg/minute, otherwise there is a risk of ototoxicity (see PRECAUTIONS). Thus the duration of infusion should be about 60 minutes. The diuresis should start during the infusion.
Additional dose: Should the initial dose fail to produce an adequate increase (at least 40 to 50 mL/hour) in urinary output, a second infusion of 500 mg (appropriately diluted) may be given 1 hour after completion of the first.
The duration of this infusion is determined by the maximum rate of frusemide 4 mg/minute. A maximum daily dose of 1000 mg should not be exceeded.
For hypervolaemic patients, it is advisable to give the high-dosage formulation of frusemide undiluted, or in a suitable volume (e.g. 250 mg in 50 mL) of infusion fluid, so as to avoid the risk of over-hydration. IV infusions of the undiluted solution must be given with the aid of a motor-driven precision syringe, so as to make sure that the upper limit of frusemide 4 mg (0.4mL) /minute is not exceeded.
If a satisfactory diuretic response is achieved (40 to 50 mL/hour), the effective dose can be repeated every 24 hours.
Parenteral therapy should be replaced by treatment with frusemide 500 mg tablets as soon as this is practical.
Use in Children
High dose Lasix preparations should not be used in children. However, normal doses of Lasix may be used (refer above).
OVERDOSAGE
The clinical picture in acute or chronic overdose depends primarily on the extent and consequences of electrolyte and fluid loss; e.g. dehydration, blood volume reduction, hypotension, electrolyte imbalance, cardiac arrhythmias (including A-V block and ventricular fibrillation), hypokalaemia and hypochloraemic alkalosis, and extensions of its diuretic action. Symptoms of these disturbances include severe hypotension (progressing to shock), acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy and confusion.
The acute toxicity of Lasix has been determined in mice, rats and dogs. In all three, the oral LD50 exceeded 1000 mg/kg body weight, while the intravenous LD50 ranged from 300 to 680 mg/kg. The acute intragastric toxicity in neonatal rats is 7 to 10 times that of adult rats. The concentration of Lasix in biological fluids associated with toxicity or death is not known.
No specific antidote to Lasix is known. If ingestion has only just taken place, attempts may be made to limit further systemic absorption of the active ingredient by measures such as activated charcoal).
Treatment of overdosage is supportive and consists of replacement of excessive fluid and electrolyte losses. Serum electrolytes, carbon dioxide level and blood pressure should be determined frequently. Adequate drainage must be assured in patients with urinary bladder outlet obstruction (such as prostatic hypertrophy). Haemodialysis does not accelerate frusemide elimination.
Contact the Poisons Information Centre for advice on management of overdosage.
PRESENTATION AND STORAGE CONDITIONS
Lasix Oral Solution for paediatric use, 10 mg/mL glass bottle (orange flavoured, 70% sorbitol solution): 30 mL. Store below 8°C. Do not freeze. Protect from light.
Lasix High Dose 250 mg/25 mL ampoules (in water for injection without solubiliser, pH about 9): 5's. Store below 25°C. Protect from light.
NAME AND ADDRESS
sanofi-aventis new zealand limited
Level 8, James and Wells Tower
56 Cawley Street
Ellerslie, Auckland
Freecall No: 0800 283 684
MEDICINE CLASSIFICATION
Prescription Only Medicine
DATE OF PREPARATION
3 July 2009