Universal reference book for medicines
Product name: LAZIX ® (LASIX ® )

Active substance: furosemide

Type: Diuretic

Manufacturer: SANOFI INDIA (India)
Composition, form of production and packaging
Tablets are
white or almost white, round, with engraved "DLI" above and below the risks on one side.

1 tab.

furosemide 40 mg

Excipients: lactose - 53 mg, starch - 56.88 mg, pregelatinized starch - 7 mg, talc - 2.4 mg, silicon dioxide colloid - 0.4 mg, magnesium stearate - 0.32 mg.

10 pieces.
- strips of aluminum foil (5) - packs of cardboard.
15 pcs.
- Strips of aluminum foil (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2016.

PHARMACHOLOGIC EFFECT

The drug Lasix ® is a strong and fast acting diuretic, which is a sulfonamide derivative.
The drug Lasix ® blocks the transport system of sodium ions (Na + ), potassium (K + ), chlorine (Cl - ) in the thick segment of the ascending knee of the Henle loop, and therefore, its diuretic effect depends on the drug entering the lumen of the renal tubules account of the anion transport mechanism). The diuretic effect of the drug Lasix ® is associated with the inhibition of the reabsorption of sodium chloride in this section of the loop of Henle. Secondary effects on the increase in sodium excretion are: an increase in the amount of urine released (due to osmotically bound water) and an increase in the secretion of potassium in the distal part of the renal tubule. At the same time, the excretion of calcium and magnesium ions increases. When the tubular secretion of furosemide decreases or when furosemide is bound to the albumin located in the lumen of the tubules (for example, in a nephrotic syndrome), the effect of furosemide decreases.
At the course of taking the drug Lasix ®, its diuretic activity does not decrease, because
the drug interrupts the tubular-glomerular feedback in Macula densa (tubular structure closely related to the juxtaglomerular complex). The drug Lasix ® causes a dose-dependent stimulation of the renin-angiotensin-aldosterone system.
With heart failure, the preparation Lasix ® quickly reduces preload (by expanding the veins), reduces pulmonary artery pressure and the filling pressure of the left ventricle.
This rapidly developing effect appears to be mediated through the effects of prostaglandins and therefore the condition for its development is the absence of disturbances in the synthesis of prostaglandins, in addition to which this effect also requires sufficient preservation of kidney function.
The drug Lasix ® has an antihypertensive effect, which is caused by an increase in sodium excretion, a decrease in the volume of circulating blood and a decrease in the response of the smooth muscle of the vessels to vasoconstrictive stimuli (due to the natriuretic effect, furosemide decreases the response of the vessels to catecholamines, whose concentration in patients with arterial hypertension is increased).

After oral administration of 40 mg of the drug Lasix ® diuretic effect begins within 60 minutes and lasts about 3-6 hours.

In healthy volunteers, who received 10 to 100 mg of the drug Lasix ® , there was a dose-dependent diuresis and sodium naresis.

PHARMACOKINETICS

Furosemide is rapidly absorbed into the digestive tract.
Its Tmax (time to reach Cmax in the blood) is from 1 to 1.5 hours. The bioavailability of furosemide in healthy volunteers is approximately 50-70%. In patients, the bioavailability of the preparation Lasix ® can be reduced to 30%; It can be influenced by various factors, including the underlying disease. V d furosemide is 0.1-0.2 l / kg body weight. Furosemide binds to blood plasma proteins (more than 98%), mainly with albumins.
Furosemide is excreted mainly unchanged and mainly through secretion in the proximal tubules.
Glucuronated furosemide metabolites are 10-20% of the kidney-excreted drug. The rest of the dose is released through the intestine, apparently through biliary secretion. The final T 1/2 of furosemide is about 1-1.5 h.
Furosemide penetrates the placental barrier and is excreted in the mother's milk.
Its concentration in the fetus and the newborn is the same as that of the mother.
Peculiarities of pharmacokinetics in selected groups of patients

With renal failure, the removal of furosemide slows down, and T 1/2 increases;
with pronounced renal failure, the final T 1/2 can be increased to 24 hours.
In the nephrotic syndrome, a decrease in plasma protein concentrations leads to an increase in the concentrations of unbound furosemide (its free fraction), which increases the risk of ototoxic action.
On the other hand, the diuretic effect of furosemide in these patients can be reduced by binding furosemide to albumin in the tubules and reducing the tubular secretion of furosemide.
With hemodialysis and peritoneal dialysis and permanent outpatient peritoneal dialysis, furosemide is not significantly excreted.

With hepatic insufficiency
T 1/2 furosemide is increased by 30-90% mainly due to an increase in V d . Pharmacokinetic parameters in this category of patients can vary greatly.
With heart failure, severe arterial hypertension and in the elderly, the excretion of furosemide slows down due to decreased kidney function.

INDICATIONS

- edematic syndrome with chronic heart failure;

- edematic syndrome with chronic renal failure;

- Acute renal failure, including those during pregnancy and burns (to maintain fluid excretion);

- edematous syndrome with nephrotic syndrome (with nephrotic syndrome in the foreground is the treatment of the underlying disease);

- edematic syndrome with liver diseases (if necessary in

addition to treatment with aldosterone antagonists);

- arterial hypertension.

DOSING MODE

General recommendations:

Tablets should be taken on an empty stomach without chewing and drinking with a sufficient amount of liquid.

When prescribing Lasix ® it is recommended to use it in the smallest doses, sufficient to achieve the desired effect.

The recommended maximum daily intake for adults is 1500 mg, in children 40 mg / day.

The duration of treatment is determined by the doctor individually, depending on the indications.

Special recommendations on the dosing regimen

Children

In children, the recommended daily intake for oral administration is 2 mg / kg body weight (but not more than 40 mg / day).

Adults

Edema syndrome with liver diseases

The drug Lasix ® is used in addition to treatment with aldosterone antagonists in case of their insufficient effectiveness.
To prevent the development of complications, such as a violation of orthostatic regulation of blood circulation, disturbance of the water-electrolyte balance or acid-base state, careful selection of the dose is required so that the fluid loss occurs gradually (at the beginning of the treatment, a loss of fluid up to about 0.5 kg of body weight per day is possible ). The recommended initial dose is 20-80 mg / day. It can be adjusted depending on the patient's response. The daily dose can be applied 1 time / day or divided into 2 doses.
Edema Syndrome in Chronic Renal Failure

The natriuretic reaction to furosemide depends on several factors, including the severity of renal failure and the sodium content in the blood, so the effect of the dose can not be exactly predictable.
Patients with chronic renal failure require a careful dose selection, by gradually increasing it so that fluid loss occurs gradually (at the beginning of treatment, a loss of fluid up to about 2 L / day, about 280 mmol Na + / day) is possible.
The recommended initial dose is a dose of 40-80 mg / day.
The necessary dose is selected depending on the diuretic response. The entire daily dose should be taken once or divided into two doses. In patients on hemodialysis, the usual maintenance dose is 250-1500 mg / day.
Acute renal failure (to maintain the excretion of fluid)

Before starting treatment with Lasix ® , hypovolemia, arterial hypotension and significant disturbances of the electrolyte and / or acid-base state should be eliminated.Treatment begins with iv administration of the preparation Lasix ® .
The recommended initial dose is 40 mg IV. If the necessary diuretic effect is not achieved, the Lasix ® preparation can be administered in the form of continuous intravenous infusion, starting at a rate of 50-100 mg per hour.
It is recommended to transfer the patient as soon as possible from the intravenous injection of Lasix ® to taking Lasik ® tablets (the dose of the tablets depends on the amount of IV taken).

Edema with nephrotic syndrome

The recommended initial dose is 40-80 mg / day.
The necessary dose is selected depending on the diuretic response. The daily dose can be taken at one time or divided into several receptions (see sections "Pharmacokinetics" and "Special instructions").
Edema Syndrome in Chronic Heart Failure

The recommended initial dose is 20-80 mg / day.
The necessary dose is selected depending on the diuretic response. It is recommended that the daily dose be divided into two or three doses.
Arterial hypertension

The drug Lasix ® can be used in monotherapy or in combination with other antihypertensive drugs.
The usual maintenance dose is a dose of 20-40 mg / day. With arterial hypertension in combination with chronic renal failure, higher doses of Lasix ® may be required.
SIDE EFFECT

Frequency of occurrence of unwanted reactions / adverse events (HP / AE) was obtained from literature and clinical studies.
If the frequency of occurrence for the same HP / A in the literature data and data from clinical trials was different, the highest incidence of HP / AH is indicated.
The following grades are used for the incidence of HP / AE according to the classification of CIOMS (Council of International Medical Scientific Organizations): very often? 10%;
often? 1% and <10%; infrequently? 0.1% and <1%; rarely 0.01% and <0.1%; very rarely <0.01%, the frequency is unknown (it is not possible to determine the incidence of HP / AH from the available data).
From the side of metabolism and nutrition

Often

Violations of the water-electrolyte balance, including those that occur with clinical symptoms.
Symptoms that indicate the development of violations of water-electrolyte balance can be headache, convulsions, tetany, muscle weakness, heart rhythm disturbances and dyspeptic disorders. These disorders can develop either gradually (for a long time) or quickly (for a very short time, for example, in the case of high doses of furosemide in patients with normal renal function). Factors contributing to the development of violations of water-electrolyte balance are the main diseases (for example, cirrhosis of the liver or heart failure), concomitant therapy, changing the water-electrolyte balance; malnutrition and drinking regimen; vomiting, diarrhea, profuse sweating.
Dehydration and hypovolemia (decrease in the volume of circulating blood), especially in elderly patients, which can lead to hemoconcentration with a tendency to develop thrombosis (see below).

Increase in the concentration of creatinine in the blood.

Increase in the concentration of triglycerides in the blood.

Often

Hyponatremia, hypochloraemia, hypokalemia, increased cholesterol concentration in the blood.

Increased concentration of uric acid in the blood and gout attacks.

Infrequently

Decreased glucose tolerance.
Possible manifestation of latent diabetes mellitus (see section "Special instructions").
Frequency unknown

Hypocalcemia, hypomagnesemia, increased urea concentration in the blood, metabolic alkalosis, Barter's pseudosyndrome with incorrect and / or prolonged use of furosemide.

From the side of the vessels

Very often (for intravenous infusion)

Decrease in blood pressure, including orthostatic hypotension (this AE mainly refers to the parenteral use of furosemide).

Rarely

Vasculitis.

Frequency unknown

Thrombosis.

From the side of the kidneys and urinary tract

Often

Increase the volume of urine.

Rarely

Tubulointerstitial nephritis.

Frequency unknown

Increased sodium and chloride in the urine.

Urinary retention (in patients with partial obstruction of the urinary tract, see section "Special instructions").

Nephrocalcinosis / nephrolithiasis in premature infants (see section "Special instructions").
This AE applies only to the injectable dosage form of furosemide, children up to 3 years of taking tablets of the drug Lasix ® is contraindicated).
Renal failure (see section "Drug Interactions").

From the digestive system

Infrequently

Nausea.

Rarely

Vomiting, diarrhea.

Rarely

Acute pancreatitis.

From the side of the central nervous system

Often

Hepatic encephalopathy in patients with hepatocellular insufficiency (see section "Contraindications").

Rarely

Parasthesia.

Hearing disorders and labyrinthine disorders

Infrequently

Hearing disorders, usually transient, especially in patients with renal failure, hypoproteinemia (eg, with nephrotic syndrome).
There have been reported cases of deafness, sometimes irreversible, after taking furosemide by mouth or intravenously.
Rarely

Noise in ears.

From the skin and subcutaneous tissues

Infrequently

Skin itching, urticaria, rash, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, photosensitivity reactions.

Frequency unknown

Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, DRESS-syndrome: drug rash with eosinophilia and systemic symptoms.

From the immune system

Rarely

Severe anaphylactic or anaphylactoid reactions until the development of anaphylactic shock.

Frequency unknown

Weighting the course or exacerbation of systemic lupus erythematosus.

On the part of the blood and lymphatic system

Often

Hemoconcentration.

Infrequently

Thrombocytopenia.

Rarely

Leukopenia, eosinophilia.

Rarely

Agranulocytosis, aplastic anemia or hemolytic anemia.

Congenital, hereditary and genetic disorders

Frequency unknown

An increased risk of non-invasion of the ductus arteriosus, when furosemide is administered to premature infants during the first weeks of life (applies only to the parenteral dosage form).

General disorders and disorders at the site of administration

Rarely

Fever.

Because
Some adverse reactions (such as changes in the blood picture, severe anaphylactic or anaphylactoid reactions, severe skin allergic reactions) may, under certain conditions, threaten the life of patients, then any side effects should be reported immediately to the doctor.
CONTRAINDICATIONS

- Renal insufficiency with anuria (in the absence of reaction to furosemide);

- hepatic coma and precoma associated with hepatic encephalopathy;

- pronounced hypokalemia;

- pronounced hyponatraemia;

- hypovolemia (with a decrease in blood pressure or without a decrease in blood pressure) or dehydration;

- pronounced violations of the outflow of urine of any etiology (including unilateral urinary tract damage);

- Intoxication with cardiac glycosides;

- acute glomerulonephritis;

- Decompensated aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy;

- Increase in central venous pressure (more than 10 mm Hg);

- Children's age up to 3 years (solid dosage form);

- Pregnancy (see the section "Pregnancy and the period of breastfeeding");

- the period of breastfeeding (see the section "Pregnancy and the period of breastfeeding");

- hypersensitivity to the active substance or to any of the components of the drug;
in patients with allergies to sulfonamides (sulfonamide antimicrobial agents or sulfonylureas), there may be a cross-allergy to furosemide.
With caution: arterial hypotension;
conditions in which excessive reduction in blood pressure is particularly dangerous (stenosing lesions of coronary and / or cerebral arteries); acute myocardial infarction (increased risk of developing cardiogenic shock), latent or manifested diabetes mellitus; gout; hepatorenal syndrome (ie, with functional renal failure associated with liver disease); hypoproteinemia, for example, with nephrotic syndrome, which may reduce the diuretic effect and increase the risk of development of ototoxic effect of furosemide, so the dose selection in such patients should be carried out with extreme caution); partial obstruction of the urinary tract (hyperplasia of the prostate, narrowing of the urethra, increased risk of development of water-electrolyte balance disorders and acid-base state or in the case of significant fluid loss (vomiting, diarrhea, excessive sweating - requires monitoring of the water-electrolyte balance and acid- the basic condition and, if necessary, the correction of their disorders before the application of furosemide)); pancreatitis, ventricular arrhythmias in the anamnesis; systemic lupus erythematosus;simultaneous administration of risperidone in elderly patients with dementia (risk of increased mortality).
PREGNANCY AND LACTATION

Furosemide crosses the placental barrier, so it should not be administered during pregnancy without severe medical conditions .. If the life-saving medication Lasix ®appointed pregnant, you need to careful monitoring of the fetal development.
During lactation the drug Lasix ® is contraindicated, since it suppresses lactation.
Women should not breast-feed if they are taking medication Lasix ® .
APPLICATION FOR FUNCTIONS OF THE LIVER

Do not use this drug to patients with renal failure with anuria (no response to furosemide).
Precautions apply to patients with hepatorenal syndrome (i.e., at a functional renal failure associated with liver disease).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Do not use this drug to patients with hepatic coma and precoma associated with hepatic encephalopathy.
APPLICATION FOR CHILDREN

Do not use this medication for children up to 3 years (the solid dosage form).
APPLICATION IN ELDERLY PATIENTS

With care, while the appointment of the drug risperidone in elderly patients with dementia (risk of increased mortality).
SPECIAL INSTRUCTIONS

Before treatment drug Lasix ® should exclude the presence of very pronounced disorders of urine outflow, including and unilateral. Patients with partial violation of urine outflow require careful monitoring, especially at the beginning of treatment with Lasix ® .
During treatment with Lasix ® requires regular monitoring of sodium, potassium, and creatinine concentration in blood serum, especially careful control should be performed in patients with high risk of disturbances of water-electrolyte balance in cases additional loss of fluid and electrolytes (e.g., due to vomiting diarrhea, or heavy sweating).
Before and during treatment with Lasix ®must be monitored and, in case of, eliminate hypovolemia or dehydration, as well as clinically significant fluid and electrolyte disturbances and / or acid-base balance, which may require a brief cessation of drug treatment Lasix ® .
When treating drug Lasix ® it is always advisable to eat foods rich in potassium (lean meat, potatoes, bananas, tomatoes, cauliflower, spinach, dried fruits, etc.). In some cases potassium reception drugs may be shown or appointment sparing drugs.
In patients with hypoproteinaemia, eg associated with nephrotic syndrome (possibly weakening the effectiveness of furosemide and increase its ototoxicity). It requires careful dose escalation.
There was a high incidence of deaths in elderly patients with dementia, simultaneously treated with risperidone and furosemide in comparison to those treated with furosemide or only or only risperidone. Farmakofiziologichesky mechanism of this effect is not installed. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with increased mortality in elderly patients with dementia. Elderly patients with dementia with caution, carefully weighing the risk-benefit ratio and apply furosemide and risperidone at the same time. Because Dehydration is a common risk factor for increased mortality,when deciding on the use of this combination in elderly patients with dementia to avoid dehydration of the patient.
There is a possibility of weighting the current or exacerbation of systemic lupus erythematosus.
Selection of dosing regimen in patients with ascites on the background of liver cirrhosis should be performed in a hospital (violation of water and electrolyte balance may lead to the development of hepatic coma).
Impact on the ability to drive vehicles and manage mechanisms

Some side effects (eg, significant reduction in blood pressure) may interfere with the ability to concentrate and reduce the psychomotor reactions, which can be dangerous while driving or occupation of other potentially hazardous activities. This applies particularly to the period of the start of treatment or increasing the dose, as well as in cases of simultaneous reception antihypertensives or ethanol.
In such cases, it is not recommended to drive vehicles or to engage in potentially hazardous activities.
OVERDOSE

If you suspect an overdose need to be sure to see a doctor because In case of overdose you may need to carry out certain remedial measures.
The clinical picture of acute or chronic overdose depends primarily on the extent and consequences of the loss of fluid and electrolytes; overdose can manifest hypovolemia, dehydration haemoconcentration, disorders of heart rhythm and conduction (including AV-blockade and ventricular fibrillation). The symptoms of these disorders are arterial hypotension (up to the development of shock), acute renal failure, thrombosis, delirium, flaccid paralysis, apathy and confusion.
There is no specific antidote. If the ingestion was not long, then to reduce the absorption of furosemide from the intestine should try to induce vomiting or to gastric lavage, and then ingest activated charcoal. Treatment is aimed at correcting disorders clinically significant fluid and electrolyte and acid-base status under the control of serum concentrations of electrolytes, acid-base indicators of status, hematocrit, as well as the prevention or treatment of possible serious complications developing against the background of these disorders.
DRUG INTERACTION

Not recommended combinations
Chloral hydrate - in / infusion of furosemide in 24-hour period after administration of chloral hydrate may cause skin flushing, sweating, restlessness, nausea, increased blood pressure and tachycardia. Therefore it is not recommended to use furosemide together with chloral hydrate.
Aminoglycosides - slowing kidney excretion of aminoglycosides in their simultaneous use with furosemide and increased risk of ototoxicity and nephrotoxicity of aminoglycosides. For this reason, to avoid the use of this combination of drugs except when necessary for health reasons, in which case the required correction (reduction) maintenance doses of aminoglycosides.
Cardiac glycosides, drugs that cause QT interval elongation -to case of development in patients receiving furosemide electrolyte abnormalities (hypokalemia or hypomagnesemia) increases the toxic effect of cardiac glycosides and drugs that cause QT interval prolongation (risk of arrhythmias increases).
Corticosteroids, carbenoxolone, liquorice in large amounts and prolonged use of laxatives in combination with furosemide increase the risk of hypokalemia.
Drugs with nephrotoxic action - when combined with furosemide increases their risk of developing nephrotoxicity.
High doses of certain cephalosporins (especially those with predominantly renal route of elimination) - in conjunction with furosemide increases the risk of nephrotoxicity.
Cisplatin - the simultaneous use of furosemide there is a risk of ototoxic action. Furthermore, in case of a joint assignment cisplatin and furosemide in doses above 40 mg (normal kidney function) increases the risk of nephrotoxicity of cisplatin.
Combinations, which when applied caution
ototoxic drugs - furosemide potentiates their ototoxicity. Such formulations can be applied simultaneously with the drug Lasix ®only under strict medical indications, as the combined use can lead to irreversible damage to the auditory organ.
Cisplatin - while the use of medication Lasix ® there is a risk of ototoxic action. In addition, the possible increase of nephrotoxicity of cisplatin in the application of furosemide for forced diuresis during cisplatin treatment, if furosemide is not applicable to low doses (e.g. 40 mg in patients with normal renal function) or in conjunction with appropriate patient hydration.
ACE inhibitors and angiotensin II receptor - assignment of an ACE inhibitor or an angiotensin II receptors in patients previously treated with furosemide may lead to excessive decrease of blood pressure with the deterioration of kidney function, and in some cases - to the development of acute renal failure, so for three days prior to treatment or increasing doses of ACE inhibitors or angiotensin II receptor antagonists furosemide recommended abolition or reduction in the dose.
Lithium salts - under the influence of furosemide is reduced lithium excretion, thereby increasing the lithium content in the blood serum, which increases the risk of its toxic effect, including its damaging effects on the heart and nervous system. Therefore, when using this combination requires monitoring of lithium in blood serum.
Risperidone - care must be taken carefully weighing the balance between risks and benefits before using a combination of risperidone with furosemide or other potent diuretics because of the fact that there was an increase in mortality in elderly patients with dementia treated with simultaneous treatment with risperidone and furosemide.
Interactions which should be taken into account
Cardiac glycosides, drugs causing prolongation of the QT- interval in the case of the use of furosemide in the background of violations of water-electrolyte imbalance (hypokalemia or hypomagnesemia) increases the toxic effects of cardiac glycosides and means causing elongation of the QT interval (increasing the risk of heart rhythm disturbances).
Corticosteroids, carbenoxolone, liquorice products in large quantities and prolonged use of laxatives in combination with furosemide increase the risk of hypokalemia.
Drugs with nephrotoxic action - when combined with furosemide increases their risk of developing nephrotoxicity. High doses of certain cephalosporins (are excreted primarily by the kidneys) - in conjunction with furosemide increase the risk of nephrotoxicity of cephalosporins.
Nonsteroidal anti-inflammatory drugs (NSAIDs) - NSAIDs, including aspirin, can reduce the diuretic effect of furosemide. In patients with hypovolemia and dehydration (including in patients receiving furosemide) NSAIDs may cause the development of acute renal failure. Furosemide can amplify the toxic effect of salicylates.
Phenytoin - reducing the diuretic effect of furosemide.
Antihypertensives, diuretics or other agents capable of lowering blood pressure - in combination with furosemide expected more pronounced hypotensive effect.
Probenecid, methotrexate or other drugs that as furosemide, secreted in the renal tubules, can reduce the effects of furosemide (same path renal secretion), on the other hand furosemide may reduce renal excretion of these drugs.
Hypoglycemic agents, for oral administration, and formulations of insulin pressor amines (epinephrine, norepinephrine) - attenuation effects when combined with pressor amines (epinephrine, norepinephrine) - attenuation effects in combination with furosemide.
Theophylline, diazoxide, Curariform relaxants - strengthening effects when combined with furosemide.
Sucralfate - reducing suction furosemide and its attenuation effect (furosemide and sucralfate should be taken at intervals of not less than 2 hours).
Cyclosporin A - when combined with furosemide increased risk of gout due to hyperuricemia caused furosemide, and impaired kidney urate excretion influenced cyclosporin.
Radiopaque substances - in patients at high risk of developing nephropathy for administering contrast media receiving furosemide, there was a higher incidence of renal function compared to patients with high risk of nephropathy for administering contrast agents, which prior to introducing the radiopaque preparation was conducted only on / in the introduction fluid (hydration).
TERMS OF RELEASE FROM PHARMACY

The drug is available on prescription.
TERMS AND CONDITIONS OF STORAGE

The drug should be protected from light, out of reach of children at a temperature not higher than 30 ° C. Shelf life - 4 years.
Do not use beyond the expiration date printed on the package.
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