Lasix

Interactions with herbal product have not been established.

Interactions with food have not been established.

Interactions with other drugs have not been established.

Interactions with laboratory tests have not been established.

Sulfonamide diuretics have been reported to decrease arterial responsiveness to pressor amines and to enhance the effect of tubocurarine or curare-type muscle relaxants. (See Warnings and Precautions, Peri-Operative Considerations.)

In case of concomitant abuse of laxatives, the risk of an increased potassium loss should be considered.

Glucocorticoids, carbenoxolone and licorice may also increase potassium loss.

Administration of LASIX to diabetic patients may result in possible decrease of diabetic control. Dosage adjustments of the anti-diabetic agent may be needed.

Hearing impairment is more likely to occur in patients who are also receiving drugs known to be ototoxic (e.g. aminoglycosides antibiotics, ethacrynic acid and cisplatin) (see Warnings and Precautions).

In edematous hypertensive patients being treated with antihypertensive agents, care should be taken to reduce the dose of these drugs when LASIX is administered, since LASIX potentiates their hypotensive effect.

Non-steroidal anti-inflammatory drugs (e.g. indomethacin, acetyl-salicylic acid) may attenuate the effect of LASIX and may cause renal failure in case of pre-existing hypovolemia.

A dosage schedule of 20 to 40 mg twice daily is recommended. Individualized therapy is of great importance. It is further recommended, if 40 mg twice daily does not lead to a clinically satisfactory response, to add other antihypertensive agents, rather than to increase the dose of LASIX.

Careful observations for changes in blood pressure must be made when LASIX is used with other antihypertensive drugs, especially during initial therapy. The dosage of other agents must be reduced by at least 50% as soon as LASIX is added to the regimen to prevent excessive drop in blood pressure. 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.

The usual initial dose of LASIX is 40 to 80 mg. Ordinarily a prompt diuresis ensues and the starting dose can then be maintained or even reduced. If a satisfactory diuresis has not occurred within 6 hours, succeeding doses should be increased by increments of 20 to 40 mg, if necessary. Maximum daily dose: 200 mg. Once the effective single dose has been determined, it may be repeated 1 to 3 times a day.

The mobilization of edema may be most efficiently and safely accomplished by utilizing an intermittent dosage schedule in which LASIX is given for 2 to 4 consecutive days each week. With doses exceeding 120 mg/day, careful clinical and laboratory observations are particularly advisable.

LASIX therapy should be instituted in the hospital, in carefully selected patients, under close observation with frequent monitoring of serum electrolytes.

Orally, the initial dose should be in the range of 0.5 to 1 mg/kg body weight.

The total daily dose (given in divided doses of 6 to 12 hours apart) should not exceed 2 mg/kg orally. In the newborn and in premature babies, the daily dose should not exceed 1 mg/kg.

An intermittent dosage schedule should be adopted as soon as possible using the minimum effective dose at the longest possible intervals. Particular caution with regard to potassium levels is always desirable when LASIX is used in infants and children.

Xanthopsia and blurred vision have been reported.

Adverse reactions are categorized below by body system.

Electrolyte depletion has occurred during therapy with LASIX, especially in patients receiving higher doses with a restricted salt intake. Electrolyte depletion manifests itself by adverse reactions attributed to various body systems: weakness, dizziness, drowsiness, polyuria, polydipsia, orthostatic hypotension, lethargy, sweating, bladder spasms, anorexia, vomiting, mental confusion, meteorism, thirst, headache, muscle cramp, muscle weakness, tetany and disorder of cardiac rhythm. (See Warnings and Precautions.)

The development of electrolyte disturbances is influenced by factors such as underlying diseases (e.g. liver cirrhosis, cardiac failure), concomitant medication and nutrition.

Treatment with LASIX has occasionally caused some deterioration of metabolic control in cases of manifest diabetes, or has made latent diabetes manifest.

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.

Pre-existing metabolic alkalosis (e.g. in decompensated cirrhosis of the liver) may be aggravated.

In extreme cases, hypovolemia may lead to dehydration, circulatory collapse, hemoconcentration and thrombophilia. Thrombophlebitis and emboli have been reported.

Jaundice (intrahepatic cholestatic jaundice) has been reported.

No data available.

Too vigorous diuresis may induce orthostatic hypotension or acute hypotensive episodes, which may cause signs and symptoms such as impairment of concentration and reactions, lightheadedness or orthostatic intolerance.

Cases of tinnitus and reversible deafness have been reported. There have also been some reports of cases, the majority in children undergoing renal transplantation, in which permanent deafness has occurred. In these latter cases, the onset of deafness is usually insidious and gradually progressive up to 6 months after furosemide therapy. Hearing impairment is more likely to occur in patients with hypoproteinaemia or severely reduced renal function who are also receiving drugs known to be ototoxic.

Vertigo has been reported.

At the commencement of treatment, excessive diuresis may give rise, especially in elderly patients, to a feeling of pressure in the head, dizziness.

Paresthesia has been reported.

Hepatic encephalopathy in patients with hepatocellular insufficiency has been reported.

Symptoms of obstructed micturition (e.g. in hydronephrosis, prostatic hypertrophy, ureterostenosis) may become manifest or may be aggravated during medication with diuretics. Interstitial nephritis has been reported.

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.

Increase in liver transaminases has been reported.

Transient elevations of BUN have been observed, especially in patients with renal insufficiency.

As with other diuretics, there may be a transient rise in serum creatinine, uric acid (this may lead to gout attack in predisposed patients), cholesterol and triglyceride levels during furosemide treatment.

Anemia, eosinophilia, leukopenia and thrombocytopenia (with purpura) have occurred, as well as agranulocytosis, aplastic anemia and hemolytic anemia.

Various forms of dermatitis (e.g. dermatitis bullous), including urticaria, erythema multiforme, bullous pemphigoid, exfoliative dermatitis, pruritus and epidermolysis bullosa have occurred. Dermatologic reactions to furosemide also include purpura and rash.

Hypersensitivity reactions to furosemide also include photosensitivity, paresthesia and fever. Systemic hypersensitivity reactions include vasculitis and necrotizing angiitis.

Severe anaphylactic or anaphylactoid reactions (e.g. with shock) occur rarely.

Acute pancreatitis, oral and gastric burning, diarrhea, nausea, vomiting and constipation have been reported. Rare occurrence of sweet taste has been reported.

Use in the geriatric population is associated with differences in safety (see Warnings and Precautions).

When administered to children, LASIX therapy should be instituted in the hospital, in carefully selected patients, under close observation with frequent monitoring of serum electrolytes. (See Dosage and Administration.)

The available pediatric data does not allow for a recommendation of a specific age range in this population.

Dehydration, electrolyte depletion and hypotension may be caused by overdosage or accidental ingestion. In cirrhotic patients, overdosage might precipitate hepatic coma.

The clinical picture in acute or chronic overdose depends primarily on the extent and consequences of electrolyte and fluide loss, e.g. hypovolemia, dehydration, hemoconcentration, cardiac arrhythmias (including A-V block and ventricular fibrillation). Symptoms of these disturbances include severe hypotension (progressing to shock), acute renal failure, thrombosis, delirious states, flaccid paralysis, apathy and confusion.

The drug should be discontinued and appropriate corrective treatment applied: 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).

Each mL of clear, slightly yellowish solution with an orange odor, contains: furosemide 10 mg. Nonmedicinal ingredients: alcohol, butylated hydroxyanisol, butylated hydroxytoluene, glycerin, methylparaben, natural orange flavor, polysorbate 80 non-animal, potassium sorbate, purified water, sodium hydroxide and sorbitol. Bottles of 120 mL.

Each yellow, round tablet, debossed with the Hoechst logo on one face, and the other face single scored with “LASIX®” debossed above score and “40" debossed below score line, contains: furosemide 40 mg. Nonmedicinal ingredients: colloidal silicon dioxide, D&C Yellow #10, FD&C Yellow #6, lactose monohydrate, magnesium stearate, purified water, starch and talc. Blister packs of 30 (2×15).

Each white, round tablet, with one surface debossed “DLF” and the other debossed with the Hoechst logo, contains: furosemide 20 mg. Nonmedicinal ingredients: colloidal silicon dioxide, lactose monohydrate, magnesium stearate, purified water, starch and talc. Blister packs of 30 (2×15).

It may be advisable to hospitalize patients with hepatic cirrhosis and ascites prior to initiating therapy. 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. Supplemental potassium chloride and, if required, an aldosterone antagonist, are helpful in preventing hypokalemia and metabolic alkalosis. (See Contraindications.)

Particularly careful monitoring is necessary in patients with hepatorenal syndrome.

Excessive diuresis induced by LASIX may result in dehydration and reduction of blood volume, with circulatory collapse and with the possibility of vascular thrombosis and embolism particularly in elderly patients. LASIX may cause electrolyte depletion.

Furosemide binding to albumin may be reduced in elderly patients.

The drug is known to be substantially excreted unchanged by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal functions, care should be taken in dose selection and may be useful to monitor renal function.

In general dose selection for the elderly patients should be cautious, usually starting at the low end of dosage range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and the concomitant disease or other drug therapy.

Sulfonamide diuretics have been reported to decrease arterial responsiveness to pressor amines and to enhance the effect of tubocurarine. Great caution should be exercised in administering curare or its derivatives to patients undergoing therapy with LASIX and it is advisable to discontinue LASIX for one week prior to any elective surgery.

LASIX (furosemide) is a potent diuretic which if given in excessive amounts can lead to a profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required, and dose and dose schedule have to be adjusted to the individual patient's needs (see Dosage and Administration).

All patients receiving LASIX therapy should be observed for signs and symptoms of fluid or electrolyte imbalance, hyponatremia, hypochloremic alkalosis, hypovolemia, hypomagnesemia, or hypocalcemia: dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oligourea, tachycardia, arrhythmia, or gastro-intestinal disturbances such as nausea and vomiting, increases in blood glucose and alteration in glucose tolerance tests.

During long-term therapy a high-potassium diet is recommended. Potassium supplements may be required especially when high doses are used for prolonged periods. Some electrolyte disturbances (e.g. hypokalemia, hypomagnesemia) may increase the toxicity of certain other drugs (e.g. digitalis preparations and drugs inducing QT interval prolongation syndrome. Particular caution with potassium levels 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 LASIX therapy may be required.

Since rigid sodium restriction is conducive to both hyponatremia and hypokalemia, strict restriction in sodium intake is not advisable in patients receiving LASIX therapy.

In in-vitro tests on bacteria and mammalian cells, both positive and negative results have been obtained. Induction of gene and chromosome mutations, however, has been observed only where furosemide reached cytotoxic concentrations.

Furosemide in the approximate amount of 200 mg/kg body weight daily was administered to female mice and rats over a 2-year period with their diet. An increased incidence of mammary adenocarcinoma was noted in the mice, but not in the rats. These tumors occurred with a positive trend, and the incidence in the high dose group was increased compared to the control, in addition, the high-dose rate was about five fold over the historical rate. These tumors are considered to be associated with furosemide administration. This dose is considerably greater than the therapeutic dose administered in human patients.

In a carcinogenicity study, rats were administered furosemide in daily doses of 15 and 30 mg/kg body weight. Male rats in the 15 mg/kg-dose category, but not in the 30 mg/kg-dose category, showed a marginal increase in uncommon tumours.

Frequent serum electrolyte and CO₂ content determinations should be performed during the first few months of therapy and periodically thereafter. It is essential to replace electrolyte losses and to maintain fluid balance so as to avoid any risk of electrolyte depletion (hyponatremia, hypochloremia, hypokalemia, hypomagnesemia or hypocalcemia), hypovolemia, or hypotension.

Checks on urine and blood glucose should be made at regular intervals especially in diabetics and in those suspected of latent diabetes when receiving LASIX. Increases in blood glucose and alterations in glucose tolerance tests with abnormalities of the fasting and two-hour postprandial blood sugar levels have been observed.

Frequent BUN determinations during the first few months of therapy and periodically thereafter, as well as regular observations for possible occurence of blood dyscrasias, liver damage or idiosyncratic reactions are advisable.

Particularly careful monitoring is necessary in:

• patients with hypoproteinaemia. Cautious dose titration is required.

  
  

• premature infants. Renal function must be monitored and renal ultrasonography performed.

  
  

• patients who would be at particular risk from a pronounced fall in blood pressure.

  
  

• patients with hepatorenal syndrome.

Increases in blood glucose and alterations in glucose tolerance tests with abnormalities of the fasting and two-hour postprandial blood sugar levels have been observed. Rare cases of precipitation of diabetes mellitus have been reported.

Asymptomatic hyperuricemia can occur and a gout attack may rarely be precipitated.

LASIX may lower the state of patient alertness and/or reactivity particularly at the start of treatment as a result of a reduction in blood pressure and of other adverse reactions (see Adverse Reactions).

LASIX may lower serum calcium levels, and rare cases of tetany have been reported. Accordingly, periodic serum calcium levels should be obtained.

In premature infants LASIX may precipitate nephrocalcinosis/nephrolithiasis. When administered to premature infants with respiratory distress syndrome in the first few weeks of life, diuretic treatment with LASIX may accentuate the risk of a patent ductus arteriosus. (See Warnings and Precautions, Monitoring and Laboratory Tests.)

Caution is required in neonates because of prolonged half-life of furosemide.

The teratogenic and embryotoxic potential of furosemide in humans is unknown. The drug should not be used in pregnant women or in women of childbearing potential unless in the opinion of the attending physician the benefits to the patient outweigh the possible risk to the fetus.

Reproductive and teratological studies have been performed in mice, rats, rabbits, cats, dogs and monkeys. With the exception of mice and rabbits, no abnormalities attributed to furosemide were detected. Furosemide caused unexplained maternal deaths and abortions in the rabbit at a daily dose of 50 mg/kg (approximately three times the maximum recommended human daily dose of 1000 mg orally) when administered between days 12 to 17 of gestation. In another study in rabbits, a dose of 25 mg/kg caused maternal deaths and abortions. In a third study, none of the pregnant rabbits survived a dose of 100 mg/kg. Data from the above studies indicate fetal lethality which can precede maternal deaths.

The results of a mouse study and one of the three rabbit studies also showed an increased incidence of distention of the renal pelvis and, in some cases, of the ureters in fetuses derived from treated dams as compared to the incidence of fetuses from the control group.

Treatment during pregnancy requires monitoring of fetal growth.

It should be noted that diuretics may partially inhibit lactation and that LASIX passes into the breast milk. Women must not breast-feed if they are treated with furosemide (see Contraindications).

Cases of tinnitus and reversible deafness have been reported. There have also been some reports of cases, the majority in children undergoing renal transplantation, in which permanent deafness has occurred. In these latter cases, the onset of deafness was usually insidious and gradually progressive up to 6 months after furosemide therapy. Hearing impairment is more likely to occur in patients with hypoproteinaemia or severely reduced renal function or in patients who are also receiving drugs known to be ototoxic. Since this may lead to irreversible damage, these drugs must only be used with furosemide if there are compelling medical reasons.

Tablets: Store between 15 and 30°C. Protect from light.

Oral solution: Store between 15 and 30°C. Protect from light.

In liver failure, the half-life of furosemide is increased by 30% to 90% mainly due to a larger volume of distribution. Additionally, in this patient group there is a wide variation in all pharmacokinetic parameters.

The elimination of furosemide is slowed down due to reduced renal function in the elderly.

In man, LASIX is rapidly absorbed from the gastro-intestinal tract. The diuretic effect of furosemide is apparent within one hour following oral administration and the peak effect occurs in the first or second hour. The duration of action is 4-6 hours but may continue up to 8 hours.

Following intravenous administration of the drug, the diuresis occurs within 30 minutes and the duration of action is about 2 hours.

Animal experiments using stop-flow and micropuncture techniques have demonstrated that LASIX inhibits sodium reabsorption in the ascending limb of Henle's loop as well as in both proximal and distal tubules. The action of LASIX on the distal tubule is independent of any inhibitory effect on carbonic anhydrase or aldosterone.

LASIX may promote diuresis in cases which have previously proved resistant to other diuretics.

Data unavailable.

In renal failure, the elimination furosemide is slowed down and the half-life prolonged; the terminal half-life may be up to 24 hours in patients with severe renal failure.

In nephrotic syndrome the reduced plasma protein concentration leads to a higher concentration of unbound (free) furosemide. On the other hand, efficacy of furosemide is reduced in these patients due to binding to intratubular albumin and lowered tubular secretion.

Furosemide is poorly dialyzable in patients undergoing haemodialysis, peritoneal dialysis and CAPD.

Data unavailable.

A small fraction is metabolized by cleavage of the side chain.

Data unavailable.

A continuous infusion of furosemide is more effective than repetitive bolus injections. Moreover, above a certain bolus dose of the drug there is no significant increase in effect.

The effect of furosemide is reduced if there is lowered tubular secretion or intra-tubular albumin binding of the drug.

Depending on the maturity of the kidney, the elimination of furosemide may be slowed down. The metabolism of the drug is also reduced if the infant’s glucuronisation capacity is impaired.

The terminal half-life is below 12 hours in infants with a post-conceptional age of more than 33 weeks.

In infants of 2 months and older, the terminal clearance is the same as in adults.