Composition, form of production and packaging
The solution for intravenous and / or injection is clear, colorless.
1 ml of 1 amp.
furosemide 10 mg 20 mg
Excipients: sodium chloride, sodium hydroxide, water d / and.
2 ml - dark glass ampoules with a break point (10) - packings of cellular contour plastic (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
Lasix В® is a high-speed diuretic, which is a sulfonamide derivative. Lasix В® blocks the transport system of Na + ions, K + , Cl - in the thick segment of the ascending knee of the Henle loop, and therefore, its saluretic effect depends on the admission of the drug into the lumen of the renal tubules (due to the mechanism of anion transport). The diuretic effect of the drug Lasix В® 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.
With the repeated administration of the drug Lasix В®, its diuretic activity does not decrease, as the drug interrupts the tubular-glomerular feedback in Macula densa (tubular structure closely related to the juxtaglomerular complex). Lasix В® causes dose-dependent stimulation of the renin-angiotensin-aldosterone system.
With heart failure, Lasix В® 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 has an antihypertensive effect, which is caused by increased sodium excretion, a decrease in the volume of circulating blood, and a decrease in the response of the smooth muscles of the vessels to vasoconstrictive effects (due to the natriuretic effect, furosemide decreases the vascular response to catecholamines, whose concentration in hypertensive patients is increased).
Dose-dependent diuresis and sodium naresis are observed with the use of Lasix В® in a dose of 10 mg to 100 mg. (healthy volunteers). After intravenous administration of 20 mg of the drug Lasix В®, the diuretic effect develops after 15 minutes and lasts about 3 hours.
The relationship between the intracanular concentrations of unbound (free) furosemide and its natriuretic effect is in the form of a sigmoid curve with a minimum effective furosemide excretion rate of about 10 Ојg / min. Therefore, prolonged infusion of furosemide is more effective than repeated bolus administration. In addition, when a certain bolus dose is exceeded, no significant increase in the effect is observed. When the tubular secretion of furosemide decreases or when the drug binds to the albumin located in the lumen of the tubules (for example, in a nephrotic syndrome), the effect of furosemide decreases.
The volume of distribution of furosemide is 0.1-0.2 l / kg body weight and varies significantly depending on the underlying disease. Furosemide binds very strongly to blood plasma proteins (more than 98%), mainly with albumins. Furosemide is excreted mainly unchanged and mainly through secretion in the proximal tubules. After intravenous administration of furosemide, 60-70% of the administered dose is excreted by this route. Glucuronated furosemide metabolites are 10-20% of the kidney-excreted drug. The remaining dose is secreted through the intestine, apparently by biliary secretion.
The final T.sub.f 1/2 furosemide after intravenous administration is about 1-1.5 hours.
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, a finite T 1/2 can increase up to 24 hours.
In a nephrotic syndrome, a decrease in plasma protein concentrations leads to an increase in the concentrations of unbound furosemide (its free fraction), and the risk of developing an ototoxic effect increases. 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.
In liver failure, T 1/2 furosemide is increased by 30-90%, mainly due to an increase in the volume of distribution. Pharmacokinetic parameters in this category of patients can vary greatly.
With heart failure, severe degree of arterial hypertension and in the elderly, excretion of furosemide slows down due to decreased kidney function.
In premature and full-term children, excretion of furosemide can slow down, which depends on the degree of maturity of the kidneys, the metabolism of the drug in infants can also be slowed down, since their glucuric ability is inferior. In children, whose age after conception exceeds 33 weeks, the final T 1/2 does not exceed 12 hours. In infants at the age of two months and older, excretion of furosemide does not differ from that in adults.
- edematic syndrome with chronic heart failure;
- edematic syndrome in acute 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 disease (if necessary in addition to treatment with aldosterone antagonists);
- edema of the brain.
- hypertensive crisis;
- maintenance of the forced diuresis at poisonings by chemical compounds, deducing kidneys in the unmodified kind.
When prescribing Lasix В® it is recommended to use its lowest doses, sufficient to achieve the necessary therapeutic effect. The drug is administered intravenously and in exceptional cases intramuscularly (when intravenous or drug administration is not possible). Intravenous administration of the drug Lasix В® is carried out only when the intake of the drug inside is not possible or there is a violation of absorption of the drug in the small intestine or if it is necessary to obtain the most rapid effect.When using the intravenous drug Lasix В® is always recommended as early as possible transfer of the patient to the reception of oral forms of Lasix В® .
When administered intravenously, Lasix В® should be administered slowly. The rate of intravenous administration should not exceed 4 mg per minute. In patients with severe renal failure (serum creatinine> 5 mg / dl), it is recommended that the intravenous rate of LasixВ® does not exceed 2.5 mg per minute. To achieve optimal efficiency and inhibition of counter-regulation (activation of the renin-angiotensin and antinatriuretic neurohumoral regulating units), a more prolonged infusion nutrient
The introduction of the drug Lasix В® in comparison with the repeated intravenous patient administration of the drug. If, after one or more bolus intravenous injections in acute conditions, there is no possibility of a permanent
intravenous infusion, it is more preferable to administer low doses with small interstitial spacing (approximately 4 hours) than intravenous bolus administration of higher doses with longer time intervals between administrations.
The solution for parenteral administration has a pH of about 9 and does not have buffer properties. At pH below 7, the active ingredient may fall into the sediment, so when diluting Lasix В®, it is necessary to strive for the pH of the resulting solution to fluctuate from neutral to slightly alkaline. You can use physiological saline for breeding. The diluted solution of Lasix В® should be used as early as possible. The recommended maximum daily dose for intravenous administration for adults is 1500 mg. In children, the recommended dose for parenteral administration is 1 mg / kg body weight (but not more than 20 mg per day). The duration of treatment is determined by the doctor individually, depending on the indications.
Special recommendations on the dosing regimen in adults :
Edema Syndrome in Chronic Heart Failure
The recommended initial dose is 20-80 mg per day. The necessary dose is selected depending on the diuretic response. It is recommended that the daily dose be administered 2-3 times.
Edema in acute heart failure
The recommended initial dose is 20-40 mg as an intravenous bolus. If necessary, the dose of Lasix В® can be adjusted depending on the therapeutic effect.
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 approximately 2 kg of body weight per day is possible).
In patients on hemodialysis , the usual maintenance dose is 250-1500 mg / day.
With intravenous administration, the dose of furosemide can be determined as follows: treatment is started with intravenous drip administration at a rate of 0.1 mg per minute, and then gradually increase the rate of administration every 30 minutes, depending on the therapeutic effect.
Acute renal failure (to maintain the excretion of fluid)
Before starting treatment with Laxix В® , hypovolemia, arterial hypotension and significant disturbances of the electrolyte and acid-base state should be eliminated. It is recommended that the patient be transferred as soon as possible from the intravenous introduction of Lasix В® to the taking of Lasix В® tablets (the dose of Lasix В®tablets depends on the selected intravenous dose). The recommended initial intravenous dose is 40 mg. If, after its administration, the necessary diuretic effect is not achieved, Lasix В® can be administered in the form of continuous intravenous infusion, starting at an administration rate of 50-100 mg per hour.
Edema with nephrotic syndrome
The recommended initial dose is 20-40 mg per day. The necessary dose is selected depending on the diuretic response.
Edema syndrome with liver diseases
Furosemide is prescribed in addition to treatment with aldosterone antagonists in case of their insufficient effectiveness. To prevent the development of complications, such as disturbing the orthostatic regulation of the circulation or disturbing the electrolyte or acid-base state, careful selection of the dose is required so that the loss of fluid occurs gradually (at the beginning of the treatment, a loss of liquid up to about 0.5 kg of body weight per day is possible). If intravenous administration is absolutely necessary, the initial dose for intravenous administration is 20-40 mg.
Hypertensive crisis, cerebral edema
The recommended initial dose is 20-40 mg by intravenous bolus administration. The dose can be adjusted depending on the effect.
Maintenance of forced diuresis in poisoning
Furosemide is administered after intravenous infusion of electrolyte solutions. The recommended initial dose for intravenous administration is 20-40 mg. The dose depends on the reaction to furosemide. Before and during treatment with Lasix В® , fluid loss and electrolyte loss should be monitored and restored.
From the side of water-electrolyte and acid-base balance:
- hyponatremia, hypochloraemia, hypokalemia, hypomagnesemia, hyppralcemia, metabolic alkalosis, which can develop as either a gradual increase in electrolyte deficiency or a massive loss of electrolytes for a very short time, for example, when high doses of furosemide are administered to patients with normal renal function.Symptoms that indicate the development of violations of the electrolyte and acid-base state can be headache, confusion, convulsions, tetany, muscle weakness, heart rhythm disturbances and dyspeptic disorders. Factors contributing to the development of electrolyte disorders are the underlying diseases (eg, liver cirrhosis or heart failure), concomitant therapy and nutrition. In particular, vomiting and diarrhea may increase the risk of hypokalemia;
- hypovolemia and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop thrombosis.
From the cardiovascular system:
- excessive decrease in arterial pressure, which, especially in elderly patients, can be manifested by the following symptoms: a violation of concentration and reaction, a feeling of "emptiness" in the head, a feeling of pressure in the head, headache, dizziness, drowsiness, weakness, visual disorders, dryness in mouth, violation of orthostatic regulation of blood circulation. Possible development, collapse, tachycardia, arrhythmias, a decrease in the volume of circulating blood.
From the side of metabolism:
- increased serum cholesterol and triglyceride levels; transient increase in the level of creatinine and urea in the blood; increased serum uric acid concentrations, which can cause or exacerbate gout;
- Decreased glucose tolerance (possible manifestation of latent diabetes mellitus).
From the urinary system:
- the appearance or strengthening of symptoms caused by partial obstruction of the urinary tract (for example, with prostatic hyperplasia, narrowing of the urethra);
- rarely - interstitial nephritis;
- Nephrocalcinosis / nephrolithiasis in premature infants.
From the digestive tract:
- rarely - nausea, vomiting, diarrhea, isolated cases of intrahepatic cholestasis, increased levels of "liver" enzymes, acute pancreatitis.
From the central nervous system, the organ of hearing:
- rarely - paresthesia;
- in rare cases - hearing impairment, usually reversible, and / or tinnitus, especially in patients with renal insufficiency or hypoproteinemia (nephrotic syndrome), as well as in case of rapid intravenous administration of the drug.
From the skin, allergic reactions:
- rarely - skin allergic reactions: itching, urticaria, other types of rash or bullous skin lesions, polymorphic erythema, exfoliative dermatitis, purpura, fever, vasculitis, photosensitivity;
- extremely rare - severe anaphylactic or anaphylactoid reactions up to shock, which until now have been described only after intravenous administration.
From the peripheral blood:
- rarely - thrombocytopenia, eosinophilia;
- in rare cases - leukopenia;
- in some cases - agranulocytosis, aplastic anemia or hemolytic anemia.
- in preterm infants, formation of calcium-containing kidney stones (nephrolithiasis) and deposition of calcium salts in the renal parenchyma (nephrocalcinosis);
- in premature infants during the first weeks of life, furosemide may increase the risk of Botalla duct preservation;
- with intramuscular injection pain in the injection site.
Since some adverse reactions (such as a change 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 immediately be reported to the attending physician.
- Renal failure in anuria, which does not respond to the administration of furosemide;
- hepatic precoma and coma;
- pronounced hypokalemia;
- pronounced hyponatraemia;
- hypovolemia (with or without arterial hypotension) or dehydration;
- pronounced violations of the outflow of urine of any etiology (including unilateral urinary tract damage);
- period of feeding with a pond;
- hypersensitivity to the active substance or to any of the components of the drug; in patients with allergy to sulfonamides (sulfa antimicrobials or sulfonylurea) may develop "cross" allergy to furosemide.
- arterial hypotension;
- under conditions in which excessive lowering of blood pressure is particularly dangerous (stenosing lesions of coronary and / or cerebral arteries);
- acute myocardial infarction (increased risk of cardiogenic shock),
- with a latent or manifest diabetes mellitus;
- at hepatorenal syndrome;
- with hypoproteinemia (eg, nephrotic syndrome, when possible to reduce the diuretic effect and increased risk of ototoxic action of furosemide, therefore titration in these patients should be performed with extreme caution);
- in case of violation of urine outflow (hyperplasia prostatic constriction of the urethra or hydronephrosis);
- with hearing loss;
- pancreatitis, diarrhea;
- with ventricular fibrillation in history;
- in systemic lupus erythematosus;
- premature infants (possibility of formation of calcium kidney stones (nephrolithiasis) and the deposition of calcium salts in the renal parenchyma (nephrocalcinosis), so regular monitoring of renal function and renal ultrasound).
PREGNANCY AND LACTATION
Furosemide crosses the placental barrier, so it should not be administered during pregnancy. If for health Lasix В® assigned pregnant women, the need for careful monitoring of the fetus.
During the period of breastfeeding is contraindicated receiving furosemide. Furosemide inhibits lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
It is used when indicated.
Is contraindicated in anuria not responding to administration of furosemide.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
It is used when indicated.
Contraindicated in hepatic coma and precoma
Before starting treatment with Lasix В® should exclude sharp expressed violations of the outflow of urine, including one-sided.
Patients with partial violation of urine outflow require careful monitoring, especially at the beginning of treatment with Lasix В® .
During treatment with Lasix В® typically requires regular monitoring of serum concentrations of sodium, potassium, and creatinine, especially careful control should be performed in patients with high risk of disorders of electrolyte balance in cases of additional fluid loss and electrolytes (e.g., due to vomiting, diarrhea or intense sweating).
Before and during treatment with Lasix В®must be monitored and, in case of, eliminate hypovolemia or dehydration, as well as clinically significant electrolyte disturbances and / or acid-base balance, which may require a brief cessation of drug treatment Lasix В® .
When treating drug Lasix В® 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.
Premature babies require regular monitoring of renal function and renal ultrasound (possibility of nephrolithiasis and nephrocalcinosis).
Some side effects (e.g., significant reduction in blood pressure and its accompanying symptoms) can disrupt the ability to concentrate, and the reaction, which can be hazardous while driving or operating machinery. 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 alcohol.
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 status may result in the development of hepatic coma).
Instructions for compatibility
Lasix В® 20 mg should not be mixed in the same syringe with other drugs.
Emergency measures in the development of anaphylactic shock
As a rule, the following measures are recommended: at the first sign (severe weakness cold sweat, nausea, cyanosis) to terminate injection, leave the needle in the vein. Along with other conventional urgent measures need to ensure a low position of the head and torso and maintain airway patency.
Emergency medication events (dosing recommendations are designed for adults with normal body weight, in the treatment of children the dosage should be reduced in proportion to body weight):
Immediate intravenous epinephrine (adrenaline) after diluting 1 mL of a standard solution of epinephrine 1: 1000 to 10 ml at first slowly added 1 ml of the solution (= 0.1 mg epinephrine) under the control of heart rate, blood pressure and heart rate). If necessary, epinephrine administration can be continued by intravenous infusion. Simultaneously with administration of epinephrine is produced intravenous corticosteroids (250-1000 mg prednisolone or methylprednisolone), which can be repeated if necessary. In addition to these activities to replenish blood volume is carried out by intravenous infusion administration of plasma expanders and / or electrolyte solutions.
If required artificial respiration, oxygen inhalation, antihistamines.
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 atrioventricular block and ventricular fibrillation). The symptoms of these disorders are the decrease of blood pressure (up to the development of shock), acute renal failure, thrombosis, delirium, flaccid paralysis, mental confusion and apathy.
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.
Cardiac glycosides, drugs that cause lengthening of the interval QT - in the case of furosemide against introduction of electrolyte abnormalities (hypokalemia or hypomagnesemia) increases the toxic effect of cardiac glycosides and drugs that cause lengthening of the interval QT (increased risk of arrhythmias).
Corticosteroids, carbenoxolone, liquorice products in large quantities and prolonged use of laxatives in combination with furosemide increase the risk of hypokalemia.
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.
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.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin may reduce diuretic effects 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 drugs capable of lowering blood pressure - in combination with furosemide expected more pronounced hypotensive effect.
ACE inhibitors - assignment of an ACE inhibitor in patients previously receiving treatment with furosemide, may cause an 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 with ACE inhibitors, or increase their dosage recommended furosemide cancellation or reduction of the dose,
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 drugs, pressor amines (epinephrine, norepinephrine) - attenuation effects in combination with furosemide.
Theophylline, diazoxide, Curariform relaxants - strengthening effects when combined with furosemide.
Lithium salts - under the influence of furosemide is reduced lithium excretion, thereby increasing serum lithium concentration and increases the risk of toxic action of lithium, including its damaging effects on the heart and nervous system. Therefore, when using this combination requires monitoring of serum lithium concentration.
Sucralfate - reducing suction furosemide and its attenuation effect (furosemide and sucralfate should be taken at intervals of not less than two hours).
Cyclosporin A - when combined with furosemide increased risk of gout due to hyperuricemia caused furosemide, cyclosporin and impaired kidney urate excretion.
Chloral hydrate - intravenous infusion at 24-hour period after using chloral hydrate may cause skin flushing, sweating, restlessness, nausea, increase in blood pressure and tachycardia.
Radiopaque substances - in patients at high risk of developing nephropathy for administering contrast agents receiving furosemide, there was a higher incidence of renal impairment as compared to patients with high risk of nephropathy for administering contrast agents who received only intravenous hydration prior to introducing the radiopaque preparation.
Intravenously administered furosemide has a slightly alkaline reaction, so it can not be mixed with the drug with a pH less than 5.5.
TERMS OF RELEASE FROM PHARMACY
TERMS AND CONDITIONS OF STORAGE
List B. Store at a temperature not higher than 25 В° C, protected from light. Keep out of the reach of children. Shelf life - 3 years.