Active ingredients: Furosemide
LASIX 250 mg / 25 ml solution for infusion
LASIX 500 mg tablets
Lasix package inserts are available for pack sizes: - LASIX 250 mg / 25 ml solution for infusion, LASIX 500 mg tablets
- LASIX 25 mg tablets
- LASIX 10 mg / ml oral solution
Why is Lasix used? What is it for?
Diuretics with greater diuretic action.
THERAPEUTIC INDICATIONS
The use of Lasix preparations of 250 mg / 25 ml solution for infusion and 500 mg tablets is indicated only in patients with very impaired glomerular filtration (FG <0.33 ml / s = 20 ml / min.):
- acute renal failure (oligoanuria), for example in the postoperative stage and septic processes;
- chronic renal insufficiency in the pre-dialysis and dialysis stage with fluid retention, in particular in chronic pulmonary edema;
- nephrotic syndrome with severely limited renal function, eg. in chronic glomerulonephritis and lupus erythematosus;
- Kimmelstiel-Wilson syndrome.
In nephrotic syndrome therapy with corticosteroids has a predominant importance. Lasix is however indicated in the case of insufficient control of edema, in patients refractory to corticosteroid therapy or in cases where the latter is contraindicated.
In case of chronic renal failure without fluid retention, a therapeutic attempt with Lasix is indicated. If diuresis remains insufficient (less than 2.5 l / day), consideration should be given to including the patient in the dialysis program; in patients in shock, adequate measures should be taken before starting saluretic therapy. "Hypovolemia and" hypotension. Severe changes in serum electrolytes and acid-base balance must also be corrected beforehand.
Contraindications When Lasix should not be used
Hypersensitivity to the active substance or to any of the excipients. Patients with allergy to sulfonamides (e.g. sulfonamide or sulfonylurea antibiotics) may experience cross-sensitivity to furosemide.
- hypovolemia or dehydration
- anuric renal failure unresponsive to furosemide
- hypokalemia
- hyponatremia
- precoma or coma, associated with hepatic encephalopathy
- overdosing from digitalis
- first trimester of pregnancy and during breastfeeding (see section Special warnings)
Precautions for use What you need to know before taking Lasix
Lasix 250 mg / 25 ml solution for infusion should not be used for i.v. injections, but only for slow venous infusion by means of pumps to control the volume or rate of infusion, in order to reduce the risk of accidental overdose.
Lasix 500 mg tablets should only be used for patients with markedly reduced glomerular filtration, otherwise there is a risk of excessive fluid and electrolyte loss.
Lasix 250 mg / 25 ml solution for infusion and 500 mg tablets have been prepared for administration only to patients with severely limited renal function.
It is necessary to ensure free urinary outflow. Increased urine output may cause or aggravate disturbances in patients with urinary tract obstruction (eg in patients with impaired bladder emptying, prostatic hyperplasia or urethral stricture). Therefore, these patients require particularly careful monitoring, especially during the initial stages of treatment.
As with all diuretics, it is recommended to start the treatment of liver cirrhosis with ascites in a hospital setting, in order to be able to intervene appropriately if a tendency to hepatic coma occurs during diuresis.
Treatment with Lasix requires regular medical checks. In particular, careful monitoring is required in the following cases:
- patients with hypotension,
- patients at particular risk following an excessive drop in blood pressure, eg. patients with significant stenosis of the coronary arteries or blood vessels supplying the brain,
- patients with latent or manifest diabetes mellitus,
- patients with gout,
- patients with hepatorenal syndrome, eg. with functional renal insufficiency associated with severe liver disease,
- patients with hypoproteinemia, eg.associated with nephrotic syndrome (the action of furosemide may be weakened and its ototoxicity enhanced). Particular caution is required in determining the dosage,
- premature infants (due to the possible development of nephrocalcinosis / nephrolithiasis); renal ultrasound and monitoring of renal function is required.
In general, regular monitoring of sodium, potassium and creatinine levels is recommended during therapy with furosemide; in particular, strict monitoring is required for patients at high risk of electrolyte imbalance or when significant further fluid elimination occurs (eg as a result of vomiting, diarrhea or intense sweating). Although the use of Lasix only rarely leads to hypokalaemia, a diet rich in potassium (potatoes, bananas, oranges, tomatoes, spinach and dried fruit) is recommended. Adequate pharmacological correction may also sometimes be necessary.
It is also advisable to carry out regular checks of blood sugar, glycosuria and, where necessary, the metabolism of uric acid.
Concomitant use with risperidone
In placebo-controlled studies of risperidone in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97 years) compared to patients treated with risperidone alone (3.1%; mean age 80 years, range 70-96 years) or furosemide alone (4.1%; mean age 80 years, range 67-90 years). Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with such an occurrence.
No pathophysiological mechanism has been identified to explain this finding, and no pattern related to cause of death has been observed. However, before deciding on the use of such a combination, caution should be exercised and the risks and benefits of this combination or co-administration with other potent diuretics should be considered. There was no increased incidence of mortality in patients taking other diuretics concomitantly with risperidone. Regardless of treatment, dehydration has been an overall risk factor for mortality and should therefore be avoided in elderly patients with dementia (see "Interactions").
To be used under direct medical supervision
Lasix does not change blood pressure values in normal blood pressure, while it is hypotensive in hypertensive; in severe forms of hypertension, treatment in association with other aids is recommended.
Interactions Which drugs or foods can modify the effect of Lasix
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Interactions with food
The possibility and the possible degree of alteration of the absorption of furosemide administered together with food seem to depend on its pharmaceutical formulation. It is recommended that the oral formulation be taken on an empty stomach.
Combinations not recommended
In isolated cases, intravenous administration of furosemide within 24 hours of chloral hydrate intake may cause skin redness, sudden sweating, agitation, nausea, increased blood pressure and tachycardia. Therefore, concomitant administration of furosemide and chloral hydrate is not recommended.
Furosemide can potentiate the ototoxicity of aminoglycosides and other ototoxic drugs. Since this can lead to irreversible damage, the above drugs can be used in combination with furosemide only in case of clear clinical need.
Precautions for use
The concomitant administration of furosemide and cisplatin carries the risk of ototoxic effects. Furthermore, the nephrotoxicity of cisplatin may be enhanced if furosemide is not administered in low doses (e.g. 40 mg to patients with normal renal function) and in the presence of a positive water balance, when furosemide is used to obtain forced diuresis. during treatment with cisplatin.
Oral administration of furosemide and sucralfate should be separated by at least 2 hours, as sucralfate reduces intestinal absorption of furosemide, thereby reducing its effect.
Furosemide reduces the elimination of lithium salts and may cause an increase in serum concentration, resulting in an increased risk of lithium toxicity including an increased risk of cardiotoxic and neurotoxic effects from lithium. Therefore, careful monitoring of lithium concentrations is recommended in patients administered this combination
Patients on diuretic therapy may present with severe hypotension and impaired renal function, including cases of renal insufficiency, particularly in conjunction with the first administration of an ACE inhibitor or angiotensin II receptor antangonist or the first time Consideration should be given to temporarily discontinuing furosemide administration or, at least, to reduce its dose 3 days before starting treatment with an ACE inhibitor or angiotensin receptor antagonist II or before increasing the dose.
Risperidone: Caution should be exercised and the risks and benefits of the combination or co-treatment with furosemide or other potent diuretics should be considered before the decision to use such combination.
See "Precautions for Use" for increased mortality in elderly patients with dementia co-treated with risperidone
To be considered carefully
Concomitant administration of non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, may reduce the effect of furosemide. In patients with dehydration or hypovolaemia, non-steroidal anti-inflammatory drugs can induce acute renal failure. Furosemide can accentuate the toxicity of salicylates.
Reduction of the effect of furosemide may occur in case of concomitant administration of phenytoin.
The harmful effects of nephrotoxic drugs can be increased.
The administration of corticosteroids, carbenoxolone and high doses of licorice, as well as the prolonged use of laxatives can increase the risk of hypokalaemia.
Certain electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia) may increase the toxicity of some drugs (e.g. digitalis preparations and drugs that induce long QT syndrome).
In case of concomitant administration of furosemide and antihypertensive drugs, diuretics or other drugs with potentially antihypertensive action, a more pronounced drop in blood pressure should be expected.
Probenecid, methotrexate and other drugs which, such as furosemide, are excreted predominantly by the kidney, can reduce the effect of furosemide. Conversely, furosemide can reduce the renal elimination of these substances. In case of treatment with high doses (both furosemide and other drugs), an increase in serum concentrations of both may occur. Consequently, the risk of adverse events due to furosemide or other concomitant therapies increases.
The effects of antidiabetic and sympathomimetic drugs (e.g. adrenaline, noradrenaline) may be diminished. The effects of curare-like muscle relaxants or theophylline can be enhanced. Renal function impairment may develop in patients receiving concomitant therapy with furosemide and high doses of certain cephalosporins.
Concomitant use of cyclosporine A and furosemide is associated with an increased risk of gouty arthritis secondary to furosemide-induced hyperuricaemia and reduced cyclosporine-induced urate excretion.
Patients at high risk of radiocontrast nephropathy treated with furosemide had a higher incidence of deterioration of renal function following administration of contrast media, compared to high-risk patients who received intravenous hydration only prior to administration of contrast media. .
Warnings It is important to know that:
Pregnancy and breastfeeding
Pregnancy
Furosemide crosses the placental barrier. In the first trimester of pregnancy, Lasix should not be administered. In the second and third trimester of pregnancy, Lasix can be used, but only in cases of urgent clinical need. Treatment during the last two trimesters of pregnancy requires fetal growth monitoring. Ask your doctor or pharmacist for advice before taking any medicine.
Feeding time
Furosemide passes into breast milk and may inhibit lactation, therefore breastfeeding should be discontinued during treatment with furosemide.
Effects on ability to drive and use machines
Some adverse events (eg. An unexpected and severe decrease in blood pressure) can compromise the patient's ability to concentrate and react and, therefore, represent a risk in situations where these abilities are of particular importance (eg. driving vehicles or using machines).
Due to its high therapeutic reserve, furosemide can induce a significant increase in saluresis even in clinical situations in which other diuretic measures are ineffective (marked renal impairment, hypoalbuminemia, metabolic acidosis).
Important information about some of the ingredients of Lasix 500mg tablets
This medicinal product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Important information about some of the ingredients of Lasix 250 mg / 25 ml solution for infusion
One vial of LASIX 250 mg / 25 ml solution for infusion contains 0.79 mmol of sodium. A maximum daily dose (7 ampoules) contains 5.53 mmol of sodium. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
For those who carry out sporting activities
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests
Dosage and method of use How to use Lasix: Dosage
Lasix 250 mg / 25 ml solution for infusion.
The rate of infusion should always be adjusted so that no more than 4 mg of furosemide / min is administered.
The pH of the ready-to-use solution for infusion should not be less than 7 because furosemide can precipitate in an acid solution.
Lasix 250 mg / 25 ml solution should not be infused together with other drugs.
If a test dose of 40-80 mg of Lasix, administered i.v. slow (about 2-5 min.), does not cause significant increase in diuresis within 30 min., infusion treatment with Lasix 250 mg can be started.
The content of one ampoule of Lasix 250 mg / 25 ml solution for infusion must be diluted in 250 ml of Ringer's isotonic solution or another neutral or alkaline isotonic solution. Taking into account the prescribed infusion rate, in this case ( 250 mg in 275 ml) the infusion lasts about 1 hour. If the patient responds to this dose, an increase in diuresis should be noted already during the infusion. From a therapeutic point of view, an increase in diuresis of at least 40-50 ml / hour will be sought.
If a satisfactory increase in diuresis is not obtained with the first dose of Lasix, a second one will be given one hour after the end of the first infusion with 2 ampoules of Lasix 250 mg / 25 ml solution for infusion (500 mg in 50 ml), diluting the contents with the appropriate solution for infusion and adjusting the volume of the infusion to the patient's state of hydration. The duration of the infusion will always be regulated by the possibility of infusing a maximum of 4 mg of active principle / min.
In the event that even with this dose the diuresis is not as desired, one hour after the end of the second infusion, a third can be carried out with 4 ampoules of Lasix 250 mg / 25 ml solution for infusion (1000 mg in 100 ml).
The above guidelines apply to the total volume of the infusion solution as well as the rate of administration. If a satisfactory diuretic effect is not achieved with this dose, a switch to dialysis should be considered.
In hypervolemic patients it is preferable, if the test dose of 40-80 mg i.v. has proved ineffective, administer the preparation of Lasix 250 mg / 25 ml solution for infusion without diluting it or add it to the volume of solution for infusion compatible with the patient's hydration status in order to avoid overhydration. Direct intravenous infusion of the contents of the vial can only be performed if a rate of administration not exceeding 4 mg furosemide / min (= 0.4 ml / min) is guaranteed.
Miscibility: furosemide, as a derivative of anthranilic acid, is soluble in an alkaline environment. The solution of Lasix 250 mg / 25 ml solution for infusion contains the sodium salt of furosemide: this solution has a pH of about 9 and has no buffering effect.
At pH values below 7 the active ingredient can precipitate and therefore, for administration by infusion, the solution of Lasix 250 mg / 25 ml solution for infusion can only be mixed with weakly alkaline or neutral solutions, with modest buffer capacity: for ex. isotonic sodium chloride solution or Ringer's solution. Acid solutions, especially those with high buffering capacity, cannot be mixed with Lasix.
However, Lasix must not be combined with other drugs in the same syringe.
Infusion solutions containing Lasix should be used immediately after their preparation.
The vials are provided with a fixed break collar.
Administration
Infusion: furosemide i.v. it should be infused slowly, without exceeding the rate of 4 mg / minute.
In patients with severe renal impairment (serum creatinine> 5 mg / dL) it is recommended not to exceed an infusion rate of 2.5 mg per minute. LASIX 500 mg tablets - oral administration
In chronic renal failure, in which the test dose of 75-150 mg of furosemide was found to be insufficient, therapy can be initiated with Lasix 500 mg tablets by administering 1/2 tablet (= 250 mg) as the first dose.
If a satisfactory increase in diuresis occurs within 4-6 hours of administration, the starting dose can be increased by 1/2 tablet every 4-6 hours.
This procedure will be repeated until the effective dose is reached, always to be established individually, which can fluctuate between 250 and 2000 mg (1/2 - 4 tablets).
The elimination of at least 2.5 l of urine per day represents the parameter to define the effective dose of furosemide administered.
Lasix 500 mg tablets are also indicated for maintenance therapy in patients who have responded positively to treatment with high doses of parenteral Lasix. To this end, the initial dose of furosemide will be administered orally, which was effective by intravenous infusion.
If within 4-6 hours from the administration of the initial dose a sufficient increase in urine output is not obtained, the dosage can be increased by 1/2 - 1 tablet (e.g. initial dose: 1 tablet, second dose: 1 and 1/2 - 2 tablets).
It is advisable to swallow Lasix 500 mg tablets with a little liquid at the same time as breakfast in the morning.
Overdose What to do if you have taken too much Lasix
If you have any questions about the use of Lasix, ask your doctor or pharmacist.
In case of accidental ingestion / intake of an overdose of Lasix, notify your doctor immediately or go to the nearest hospital.
The clinical picture following acute or chronic overdose depends primarily on the extent and consequences of the electrolyte loss, eg hypovolaemia, dehydration, haemoconcentration, cardiac arrhythmias (including AV block and ventricular fibrillation). disorders consist of severe hypotension (up to shock), acute renal failure, thrombosis, states of delirium, flaccid paralysis, apathy and confusion.
There is no known specific antidote for furosemide. If the drug has just been taken, an attempt can be made to limit the systemic absorption of the active ingredient by means of measures such as gastric lavage or such as to reduce absorption (eg activated charcoal).
Clinically relevant imbalances in the water and electrolyte balance must be corrected. Together with the prevention and treatment of both the serious complications deriving from these imbalances and other effects on the organism, corrective action may require intensive monitoring of clinical conditions, as well as adequate therapeutic measures.
In the case of patients with urination disorders, such as in the case of prostatic hypertrophy or unconsciousness, it is necessary to restore the free urinary outflow.
Side Effects What are the side effects of Lasix
Like all medicines, Lasix can cause side effects, although not everybody gets them.
Frequencies are derived from literature data from studies in which furosemide was used in a total of 1387 patients, at any dosage and in any indication. When the frequency category for the same adverse reaction was different, the higher frequency category was selected.
In the table below, the frequency of adverse reactions is reported according to the following convention:
Very common: ≥ 1/10; Common: ≥1 / 100 e
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Expiry: see the expiry date printed on the package. The expiry date refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date shown on the package.
Protect the medicine from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children
COMPOSITION
Lasix 250 mg / 25 ml solution for infusion
One vial contains: Active ingredient: furosemide sodium 266.6 mg corresponding to 250 mg of furosemide. Excipients: mannite and water for injections.
LASIX 500 mg tablets
One tablet contains: Active ingredient: furosemide 500 mg. Excipients: corn starch, lactose, cellulose powder, sodium amylopectin glycolate, talc, colloidal silicon dioxide, magnesium stearate and quinoline yellow E104
PHARMACEUTICAL FORM AND CONTENT
Solution for infusion: Box of 5 ampoules. Tablets: Box of 20 tablets
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
LASIX
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
LASIX 250 mg / 25 ml solution for infusion
One vial contains:
Active principle: furosemide sodium 266.6 mg corresponding to 250 mg of furosemide.
LASIX 500 mg tablets
One tablet contains:
Active principle: furosemide 500 mg.
Excipients: lactose 55 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Solution for infusion.
Tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
The use of Lasix preparations of 250 mg / 25 ml solution for infusion and 500 mg tablets is indicated only in patients with:
• very impaired glomerular filtration (F.G.
• acute renal failure (oligoanuria), for example in the postoperative phase in septic processes;
• chronic renal insufficiency in the pre-dialysis and dialysis stage with fluid retention, particularly in chronic pulmonary edema;
• nephrotic syndrome with severely limited renal function, for example in chronic glomerulonephritis and lupus erythematosus; Kimmelstiel-Wilson syndrome. In nephrotic syndrome, corticosteroid therapy is predominant. Lasix is however indicated in case of insufficient edema control, in patients refractory to corticosteroid therapy or in cases where the latter is contraindicated;
• chronic renal failure without fluid retention. In these patients a therapeutic attempt with Lasix is possible; if diuresis remains insufficient (less than 2.5 l / day), the patient should be included in the dialysis program;
• state of shock; before starting saluretic therapy, hypovolemia and hypotension must be resolved with adequate measures. Severe changes in serum electrolytes and acid-base balance must also be corrected beforehand.
04.2 Posology and method of administration
LASIX 250 mg / 25 ml solution for infusion
The rate of infusion should always be adjusted so that no more than 4 mg of furosemide / min is administered.
The pH of the ready-to-use infusion solution should not be below 7, as furosemide can precipitate in acidic solution.
Furosemide solution should not be infused together with other drugs.
If the test dose of 40-80 mg furosemide, administered i.v. slow (about 2-5 min.), does not cause significant increase in diuresis within 30 min., infusion treatment with Lasix 250 mg can be started.
The content of 1 ampoule of Lasix 250 mg / 25 ml solution for infusion must be diluted in 250 ml of Ringer's isotonic solution or other neutral or alkaline isotonic solution.
Taking into account the prescribed infusion rate, in this case (250 mg in 275 ml) the duration of the infusion is approximately 1 hour. If the patient responds to this dose, increased diuresis should be noted already during the infusion. From the therapeutic point of view we will try to obtain an increase in diuresis of at least 40-50 ml / hour.
If a satisfactory increase in diuresis is not obtained with the first dose of Lasix, a second one will be given one hour after the end of the first infusion with 2 ampoules of Lasix 250 mg / 25 ml solution for infusion (500 mg in 50 ml), diluting the contents with an appropriate solution for infusion and adjusting the volume of the infusion to the patient's state of hydration. The duration of the infusion will always be regulated by the possibility of infusing a maximum of 4 mg / min. Of active principle.
In the event that even with this dose the diuresis is not as desired, one hour after the end of the second infusion, a third can be carried out with 4 ampoules of Lasix 250 mg / 25 ml solution for infusion (1000 mg in 100 ml). The above guidelines apply to the total volume of the infusion solution as well as to the rate of administration.If a satisfactory diuretic effect is not achieved with this dose, the option of switching to dialysis should be considered.
In hypervolemic patients it is preferable, if the test dose of 40-80 mg i.v. has proved ineffective, administer the preparation of Lasix 250 mg / 25 ml solution for infusion without diluting it or adding it to the volume of solution for infusion compatible with the patient's hydration status in order to avoid overhydration. Direct infusion of the contents of the vial can only be carried out if the rate of administration not exceeding 4 mg of furosemide / min. (= 0.4 ml / min.) Is guaranteed.
Infusion solutions containing furosemide should be used immediately after preparation.
LASIX 500 mg tablets
In chronic renal failure, in which the test dose of 75-150 mg of furosemide was found to be insufficient, therapy can be started with Lasix 500 mg tablets, administering ½ tablet (= 250 mg) as the first dose.
If a satisfactory increase in urine output occurs within 4-6 hours of administration, the starting dose may be increased by ½ tablet every 4-6 hours.
This procedure will be repeated until the effective dose is reached, always to be established individually, which can range between 250 and 2000 mg (½ - 4 tablets).
The elimination of at least 2.5 l of urine per day represents the parameter to define the effective dose of furosemide administered.
Lasix 500 mg tablets are also indicated for maintenance therapy in patients who have responded positively to treatment with high-dose parenteral furosemide.
To this end, furosemide, which was effective by infusion, will be administered orally as the starting dose.
If a sufficient increase in urine output is not achieved within 4-6 hours after the initial dose, the dosage can be increased by ½ - 1 tablet (eg initial dose 1 tablet; second dose 1 and ½ - 2 tablets).
It is advisable to swallow Lasix 500 mg tablets with a little liquid at the same time as breakfast in the morning.
Administration
Infusion: furosemide i.v. it should be infused slowly, without exceeding the rate of 4 mg / minute. In patients with severe renal impairment (serum creatinine> 5 mg / dL) it is recommended not to exceed an infusion rate of 2.5 mg per minute.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients. Patients with sulfonamide allergy (e.g. sulfonamide or sulfonylurea antibiotics) may experience cross-sensitivity to furosemide
• Hypovolemia or dehydration
• anuric renal failure unresponsive to furosemide
• hypokalaemia
• hyponatremia
• precoma or coma associated with hepatic encephalopathy
• digital overdosing
• first trimester of pregnancy and during breastfeeding (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Lasix 250 mg / 25 ml solution for infusion should not be used for i.v. injections, but only for slow venous infusion by means of pumps to control the volume or rate of infusion, in order to reduce the risk of accidental overdose.
Lasix 500 mg tablets should only be used for patients with markedly reduced glomerular filtration, otherwise there is a risk of excessive fluid and electrolyte loss.
Lasix 250mg / 25ml solution for infusion and 500mg tablets have been prepared to be administered only to patients with severely limited kidney function.
It is necessary to ensure free urinary outflow. Increased urine output may cause or aggravate disturbances in patients with urinary tract obstruction (eg in patients with impaired bladder emptying, prostatic hyperplasia or urethral stricture). Therefore, these patients require particularly careful monitoring, especially during the initial stages of treatment.
As with all diuretics, it is recommended to start the treatment of liver cirrhosis with ascites in a hospital setting, in order to be able to intervene appropriately if a tendency to hepatic coma occurs during diuresis.
Treatment with Lasix requires regular medical checks. In particular, careful monitoring is required in the following cases:
• patients with hypotension,
• patients particularly at risk following an excessive drop in blood pressure, eg. patients with significant stenosis of the coronary arteries or blood vessels supplying the brain,
• patients with latent or manifest diabetes mellitus,
• patients with gout,
• patients with hepatorenal syndrome, eg. with functional renal insufficiency associated with severe liver disease,
• patients with hypoproteinemia, eg. associated with nephrotic syndrome (the action of furosemide may be weakened and its ototoxicity enhanced). Particular caution is required in determining the dosage,
• premature babies (due to the possible development of nephrocalcinosis / nephrolithiasis); renal ultrasound and monitoring of renal function is required.
In general, regular monitoring of sodium, potassium and creatinine levels is recommended during therapy with furosemide; in particular, strict monitoring is required for patients at high risk of electrolyte imbalance or when significant further fluid elimination occurs (eg as a result of vomiting, diarrhea or intense sweating). Although the use of Lasix only rarely leads to hypokalaemia, a diet rich in potassium (potatoes, bananas, oranges, tomatoes, spinach and dried fruit) is recommended. Adequate pharmacological correction may also sometimes be necessary.
It is also advisable to carry out regular checks of blood sugar, glycosuria and, where necessary, the metabolism of uric acid.
Concomitant use with risperidone
In placebo-controlled studies of risperidone in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97 years) compared to patients treated with risperidone alone (3.1%; mean age 80 years, range 70-96 years) or furosemide alone (4.1%; mean age 80 years, range 67-90 years). Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with such an occurrence.
No pathophysiological mechanism has been identified to explain this finding, and no pattern related to cause of death has been observed. However, before deciding on the use of such a combination, caution should be exercised and the risks and benefits of this combination or co-administration with other potent diuretics should be considered. There was no increased incidence of mortality in patients taking other diuretics concomitantly with risperidone. Regardless of treatment, dehydration was an overall risk factor for mortality and should therefore be avoided in elderly patients with dementia (see section 4.3).
To be used under direct medical supervision.
Lasix does not change blood pressure values in normal blood pressure, while it is hypotensive in hypertensive; in severe forms of hypertension, treatment in association with other aids is recommended.
Due to its high therapeutic reserve, furosemide can induce a significant increase in saluresis even in clinical situations in which other diuretic measures are ineffective (marked renal impairment, hypoalbuminemia, metabolic acidosis).
Important information about some of the ingredients
One vial of LASIX 250 mg / 25 ml solution for infusion contains 0.79 mmol of sodium. A maximum daily dose (7 ampoules) contains 5.53 mmol of sodium. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
Lasix 500 mg tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take these tablets.
04.5 Interactions with other medicinal products and other forms of interaction
Interactions with food
The possibility and the possible degree of alteration of the absorption of furosemide administered together with food seem to depend on its pharmaceutical formulation. It is recommended that the oral formulation be taken on an empty stomach.
Combinations not recommended
In isolated cases, intravenous administration of furosemide within 24 hours of chloral hydrate intake may cause skin redness, sudden sweating, agitation, nausea, increased blood pressure and tachycardia. Therefore, concomitant administration of furosemide and chloral hydrate is not recommended.
Furosemide can potentiate the ototoxicity of aminoglycosides and other ototoxic drugs. Since this can lead to irreversible damage, the above drugs can be used in combination with furosemide only in case of clear clinical need.
Precautions for use
The concomitant administration of furosemide and cisplatin carries the risk of ototoxic effects. Furthermore, the nephrotoxicity of cisplatin may be enhanced if furosemide is not administered in low doses (e.g. 40 mg to patients with normal renal function) and in the presence of a positive water balance, when furosemide is used to obtain forced diuresis. during treatment with cisplatin.
Oral administration of furosemide and sucralfate should be separated by at least 2 hours, as sucralfate reduces intestinal absorption of furosemide, thereby reducing its effect.
Furosemide reduces the elimination of lithium salts and may cause an increase in serum concentration, resulting in an increased risk of lithium toxicity including an increased risk of cardiotoxic and neurotoxic effects from lithium. Therefore, careful monitoring of lithium concentrations is recommended in patients administered this combination.
Patients on diuretic therapy may present with severe hypotension and impaired renal function, including cases of renal failure, particularly in conjunction with the first administration of an ACE inhibitor or angiotensin II receptor antagonist or the first time Consideration should be given to temporarily discontinuing the administration of furosemide or, at the very least, to reduce its dose 3 days before starting treatment with an ACE inhibitor or angiotensin receptor antagonist II before increasing the dose.
Risperidone: Caution should be exercised and the risks and benefits of the combination or co-treatment with furosemide or other potent diuretics should be considered before the decision to use such combination.
See section 4.4 for increased mortality in elderly patients with dementia co-treated with risperidone.
To be considered carefully
Concomitant administration of non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, may reduce the effect of furosemide. In patients with dehydration or hypovolaemia, non-steroidal anti-inflammatory drugs can induce acute renal failure. Furosemide can accentuate the toxicity of salicylates.
Reduction of the effect of furosemide may occur in case of concomitant administration of phenytoin.
The harmful effects of nephrotoxic drugs can be increased.
The administration of corticosteroids, carbenoxolone and high doses of licorice, as well as the prolonged use of laxatives can increase the risk of hypokalaemia.
Certain electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia) may increase the toxicity of some drugs (e.g. digitalis preparations and drugs that induce long QT syndrome).
In case of concomitant administration of furosemide and antihypertensive drugs, diuretics or other drugs with potentially antihypertensive action, a more pronounced drop in blood pressure should be expected.
Probenecid, methotrexate and other drugs which, such as furosemide, are excreted predominantly by the kidney, can reduce the effect of furosemide. Conversely, furosemide can reduce the renal elimination of these substances. In case of treatment with high doses (both furosemide and other drugs), an increase in serum concentrations of both may occur. Consequently, the risk of adverse events due to furosemide or other concomitant therapies increases.
The effects of antidiabetic and sympathomimetic drugs (e.g. adrenaline, noradrenaline) may be diminished. The effects of curare-like muscle relaxants or theophylline can be enhanced.
Renal function impairment may develop in patients receiving concomitant therapy with furosemide and high doses of certain cephalosporins.
Concomitant use of cyclosporine A and furosemide is associated with an increased risk of gouty arthritis secondary to furosemide-induced hyperuricaemia and reduced cyclosporine-induced urate excretion.
Patients at high risk of radiocontrast nephropathy treated with furosemide had a higher incidence of deterioration of renal function following administration of contrast media, compared to high-risk patients who received intravenous hydration only prior to administration of contrast media. .
04.6 Pregnancy and lactation
Pregnancy
Furosemide crosses the placental barrier. In the first trimester of pregnancy, Lasix should not be administered. In the second and third trimester of pregnancy, Lasix can be used, but only in cases of urgent clinical need. Treatment during pregnancy requires fetal growth monitoring.
Feeding time
Furosemide passes into breast milk and may inhibit lactation, therefore breastfeeding should be discontinued during treatment with furosemide.
04.7 Effects on ability to drive and use machines
Some adverse events (eg. An unexpected and severe decrease in blood pressure) can compromise the patient's ability to concentrate and react and, therefore, represent a risk in situations where these abilities are of particular importance (eg. driving vehicles or using machines).
04.8 Undesirable effects
Frequencies are derived from literature data from studies in which furosemide was used in a total of 1387 patients, at any dosage and in any indication. When the frequency category for the same adverse reaction was different, the higher frequency category was selected.
In the table below, the frequency of adverse reactions is reported according to the following convention:
Very common: ≥ 1/10; Common: ≥1 / 100 e
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
The clinical picture following acute or chronic overdose depends primarily on the extent and consequences of the electrolyte loss, eg hypovolaemia, dehydration, haemoconcentration, cardiac arrhythmias (including AV block and ventricular fibrillation). disorders consist of severe hypotension (up to shock), acute renal failure, thrombosis, states of delirium, flaccid paralysis, apathy and confusion.
There is no known specific antidote for furosemide. If the drug has just been taken, an attempt can be made to limit the systemic absorption of the active ingredient by means of measures such as gastric lavage or such as to reduce absorption (eg activated charcoal).
Clinically relevant imbalances in the water and electrolyte balance must be corrected. Together with the prevention and treatment of both the serious complications deriving from these imbalances and other effects on the organism, corrective action may require intensive monitoring of clinical conditions, as well as adequate therapeutic measures.
In the case of patients with urination disorders, such as in the case of prostatic hypertrophy or unconsciousness, it is necessary to restore the free urinary outflow.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: diuretics with major diuretic action.
A.T.C code: C03CA01.
Lasix has documented efficacy in clinical use even in those situations, such as acute renal failure, in which other diuretics are ineffective. Furosemide, in fact, due to its high therapeutic reserve, causes an increase in water and sodium elimination even in cases where glomerular filtration is severely limited (
The natriuretic effect is dose-dependent and therefore furosemide allows to obtain guided diuresis, while the urinary elimination of potassium is considerably limited. It follows that the sodium-potassium ratio is extremely favorable.
The effect of furosemide is maintained over time when the administration is continued for a long time and is only attenuated, without disappearing, in the case of sodium depletion.
The administration of furosemide also by parenteral route also makes it possible to treat all those patients who have conditions such as to cause alterations in absorption by the oral route, such as in the case of severe edema or gastrointestinal disorders.
The diuretic effect following oral administration begins within the first hour and lasts 4-6 hours; with the intravenous infusion the effect is established already during administration and lasts for the time of the infusion itself.
05.2 Pharmacokinetic properties
Furosemide is rapidly absorbed from the gastrointestinal tract. The Tmax for the tablets is approximately 1 - 1.5 hours, while for the oral solution it is 0.6 hours. Absorption of the drug demonstrates marked inter- and intra-individual variability.
Bioavailability in healthy volunteers is about 50% - 70% for the tablets and about 80% for the oral solution. In patients, the bioavailability of the drug is affected by various factors including underlying pathologies and can be reduced to 30% (e.g. in nephrotic syndrome).
Furosemide is highly bound to plasma proteins (more than 98%), mainly to albumin.
Furosemide is eliminated mainly unchanged by secretion in the proximal tubule. After intravenous administration approximately 60% - 70% of the drug is eliminated via this route. There is a glucuronised metabolite for approximately 10-20% of the total excreted in the urine. The remainder is excreted in the faeces, probably following biliary secretion.
The terminal half-life of furosemide after intravenous administration is approximately 1 - 1.5 hours.
Furosemide is excreted in breast milk. It also crosses the placental barrier and slowly passes into the fetus. In the fetus and newborn it reaches the same concentrations found in the mother.
Renal pathologies
The bioavailability of Lasix 500 mg tablets is not altered in patients with end stage renal failure. The elimination of furosemide is slowed in patients with renal insufficiency and the half-life is prolonged up to 24 hours in patients with severe renal insufficiency.
In nephrotic syndrome, reduced plasma protein concentrations lead to a higher concentration of free (unbound) furosemide. On the other hand, however, the efficacy of furosemide is reduced in these patients due to the binding to the intratubular albumin and the reduced tubular secretion.
Furosemide is poorly dialysable in patients undergoing hemodialysis, peritoneal dialysis and CAPD.
Hepatic insufficiency
In patients with hepatic insufficiency the half-life of furosemide is increased from 30% to 90% mainly due to a higher volume of distribution. In addition, in these patients there is a wide variation in all pharmacokinetic parameters.
05.3 Preclinical safety data
Acute toxicity
Studies conducted in various rodent species and in dogs by administering furosemide by mouth and intravenously revealed low acute toxicity. The LD50 of oral furosemide in mice and rats is between 1050 mg / kg and 4600 mg / kg body weight, while in the guinea pig it is 243 mg / kg. In dogs, the LD50 is about 2000 mg / kg orally and is higher than 400 mg / kg body weight by the i.v. route.
Chronic toxicity
Renal alterations (including focal fibrosis, calcification) were found at higher doses (10 to 20 times the therapeutic dose in humans) with furosemide administration for 6 and 12 months in rats and dogs.
Ototoxicity
Furosemide can interfere with transport mechanisms in the vascular stria of the inner ear, possibly resulting in hearing disturbances which are generally reversible.
Carcinogenesis
Furosemide at doses of approximately 200 mg / kg / day body weight (14,000 ppm) was administered in the diet to female mice and rats for a period of 2 years. An increased incidence of mammary adenocarcinomas was found in mice, but not rats. This dose is significantly higher than the therapeutic dose administered to humans. Furthermore, these neoplasms were morphologically identical to the spontaneous tumors observed in 2% - 8% of the controls.
Therefore it seems unlikely that the incidence of tumors is relevant in the treatment of humans. In fact, there is no evidence of an increase in the incidence of breast adenocarcinomas following the use of furosemide.On the basis of epidemiological studies a classification by carcinogenesis of furosemide in humans does not appear possible.
In a carcinogenicity study in rats, furosemide doses of 15 and 30 mg / kg body weight were administered daily. In male rats at the dose of 15 mg / kg, but not at the dose of 30 mg / kg, there was a marginal increase in uncommon tumors. These results are considered to be random.
In rats, nitrosoamine-induced bladder carcinogenicity studies revealed no evidence that furosemide may act as a promoting factor.
Mutagenesis
In in vitro studies in bacterial and mammalian cells, both positive and negative results were obtained. However, induction of genetic and chromosomal mutations was observed only when furosemide reached cytotoxic concentrations.
Reproductive toxicology
Furosemide did not impair fertility in female and male rats at daily doses of 90 mg / kg body weight and in male and female mice at oral doses of 200 mg / kg daily.
No relevant embryotoxic or teratogenic effects were observed in various mammalian species including mice, rats, cats, rabbits and dogs following treatment with furosemide. A delay in renal maturation - a reduction in the number of differentiated glomeruli - has been described in the offspring of rats treated with 75 mg / kg furosemide at days 7 - 11 and 14 - 18 of pregnancy.
Furosemide crosses the placental barrier and reaches concentrations equal to 100% of the serum concentration in the mother in the umbilical cord. To date, no malformations have been detected in humans that could be linked to exposure to furosemide. However, insufficient experience has been obtained to allow a definitive assessment of the possible harmful effects on the embryo / fetus to be formulated. Urinary production in the fetus can be stimulated in utero.
Nephrolithiasis and nephrocalcinosis have been observed in premature infants treated with furosemide.
No studies have been conducted to evaluate the effects of furosemide ingested with breast milk on the infant.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lasix 250 mg / 25 ml solution for infusion
Mannite and water for injections.
LASIX 500 mg tablets
Corn starch, lactose, cellulose powder, sodium amylopectin glycolate, talc, colloidal silicon dioxide, magnesium stearate and quinoline yellow E 104.
06.2 Incompatibility
Furosemide, as a derivative of anthranilic acid, is soluble in an alkaline environment. The solution of Lasix 250 mg / 25 ml solution for infusion contains the sodium salt of furosemide, this solution has a pH of about 9 and has no buffering effect.
At pH values below 7 the active ingredient may precipitate and therefore, for administration by infusion, the solution of Lasix 250 mg / 25 ml solution for infusion can only be mixed with weakly alkaline or neutral solutions, with modest buffer capacity: for example isotonic sodium chloride solution or Ringer's solution.
Acid solutions, especially those with high buffering capacity, cannot be mixed with Lasix
However, Lasix must not be combined with other drugs in the same syringe.
Once diluted, it is recommended to use the solution as soon as possible.
06.3 Period of validity
Lasix 250 mg / 25 ml solution for infusion
18 months
LASIX 500 mg tablets
3 years
06.4 Special precautions for storage
Protect the medicine from light.
06.5 Nature of the immediate packaging and contents of the package
Lasix 250 mg / 25 ml solution for infusion
Neutral, colored glass vials; 5 ampoules.
LASIX 500 mg tablets
Blister packs in opaque white PVC and aluminum, heat-sealed; 20 tablets of 500 mg.
06.6 Instructions for use and handling
Lasix 250 mg / 25 ml solution for infusion
The vials are provided with a fixed break collar.
07.0 MARKETING AUTHORIZATION HOLDER
Sanofi S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
LASIX 250 mg / 25 ml solution for infusion, 5 ampoules: A.I.C. n .: 023993049
LASIX 500 mg tablets, 20 tablets: A.I.C. n .: 023993037
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 22 February 1983
Last renewal date: 31 May 2005
10.0 DATE OF REVISION OF THE TEXT
October 2014
