Pharmacological properties

Pharmacodynamics. furosemide is loopback diuretic of fast action which causes manifestation of rather strong and short-term diuretic effect. furosemide is blocked by a na+k+2cl-kotransporter who is located in basal membranes of cells of a thick segment of the ascending part of a Henle's loop: the efficiency of saluretichesky effect of furosemide, thus, depends on whether medicine gets into tubules in places of gleams by the anionotransportny mechanism. the diuretic effect develops as a result of chloride sodium reabsorption inhibition in this segment of a Henle's loop. thereof fractional excretion of sodium can reach 35% of glomerular filtration of sodium. secondary effects of the increased excretion of sodium consist in the increased urine removal (thanks to osmotically connected water) and the increased distal canalicular secretion of potassium. also removal of calcium ions and magnesium increases. furosemide causes dose-dependent stimulation system renin-angiotensin-aldosteronovoy. in heart failure furosemide leads to acute reduction of warm preloading (by narrowing of capacitive venous vessels). this early vascular effect is prostaglandinoposredovanny and assumes adequate function of kidneys with activation renin-angiotenzinovoy of a system and the intact synthesis of prostaglandins. besides, thanks to natriuretic effect, inherent for it, furosemide reduces the reactivity of vessels concerning catecholamines increased at patients with ag.

Antihypertensive efficiency of furosemide is explained by the increased sodium excretion, reduced volume of blood and the reduced response of unstriated muscles of vessels to stimulation vasoconstrictors or vasoconstrictors.

Beginning of diuretic effect is observed by

within 15 min. later in/in introductions of a medicament dose.

Dose-dependent increase in a diuresis and a natriuresis noted

at the healthy volunteers receiving furosemide in a dose of 10-100 mg. Action duration at healthy volunteers is about 3 h later in/in introductions of 20 mg of furosemide.

interrelation between concentration of untied (free) furosemide in tubular bodies (defined on the basis of the speed of excretion of furosemide with urine) and natriuretic effect is expressed by

At patients in the form of a sigmoid curve with the minimum effective speed of excretion of furosemide that makes about 10 mkg/min. Thus, continuous in/in infusion of furosemide is more effective, than repeated bolyusny injections. Moreover, except a certain bolyusny medicament dose, significant increase in expressiveness of effect is not observed. The effect of furosemide decreases if there is a reduced tubular secretion or linking of medicine with albumine in tubules.

Pharmacokinetics. Furosemide is quickly absorbed in a GIT. The maximum time of absorption — 1-1.5 h. Absorption of medicine demonstrates considerable individual variability.

Bioavailability of furosemide at healthy volunteers is about 50-70% for tablets. At patients the bioavailability of medicine is affected by various factors, including the available diseases. For example, at a nephrotic syndrome the bioavailability can decrease to 30%.

Meal along with furosemide can influence furosemide absorption.

Volume of distribution of furosemide is 0.1-0.2 l/kg of body weight. The volume of distribution can be higher depending on a disease.

Furosemide (more than 98%) forms strong connections with proteins of blood plasma, especially with albumine.

Furosemide is removed by

mainly in the form of not changed medicine by secretion in a proximal tubule.

a furosemide Metabolite — the glucuronide — makes 10–20% of the substances which are contained in urine. The residual dose is removed with a stake probably by biliary secretion.

Furosemide gets into breast milk, through a placental barrier and slowly gets to a fruit. Furosemide is defined at a fruit or at the newborn in the same concentration, as at mother.

Disease of kidneys. In a renal failure the furosemide removal which is slowed down, and T _½ — extended; final T _½ can make up to 24 h at patients with a heavy renal failure.

reduced concentration of proteins in blood plasma lead

At a nephrotic syndrome to increase in concentration of untied (free) furosemide. On the other hand, the efficiency of furosemide at these patients is reduced because of linking with intratubulyarny albumine and reduced canalicular secretion.

Furosemide badly gives in to dialysis at patients to whom carry out a hemodialysis, peritoneal dialysis and chronic peritoneal dialysis in out-patient conditions.

Liver failure. In a liver failure of T _½ furosemide increases by 30–90%, mainly thanks to the bigger volume of distribution. In this group of patients a wide variety of all pharmacokinetic parameters is observed.

Stagnant heart failure, heavy AG, patients of advanced age. Because of reduced function of kidneys at such patients the removal of furosemide is slowed down.

Premature and full-term babies. Depending on the level of formation of kidneys the removal of furosemide can be slowed down. Medicine metabolism also decreases if at babies the ability to a glyukuronization is broken. Final T _½ lasts less than 12 h at a fruit 33 weeks after fertilization of an ovum are more senior. At babies 2 months final clearance same, as at adult patients are aged more senior.

Indication

Hypostases in chronic stagnant heart failure (if treatment using diuretics is necessary).

Hypostases in acute stagnant heart failure.

Hypostases in chronic kidney disease.

OPN, including at pregnant women or during childbirth.

Hypostases in liver diseases (in case of need, for addition of treatment using antagonists of Aldosteronum).

Hypertensive crisis (as the supporting means).

Solution for injections — support of an artificial diuresis.

Use

Tablet. the mode of dosing is set by the doctor individually depending on severity of disorders of water and electrolytic balance, size of glomerular filtration, weight of a condition of the patient. medicament is used usually on an empty stomach.

For adults the maximum total daily dose of Furosemida-Darnitsa should not exceed 1500 mg.

Special recommendations about a dosage for adults

In hypostases in chronic stagnant heart failure the recommended initial medicament dose for oral administration makes 40 mg/days. In case of need it is possible to regulate a dose depending on the therapeutic answer of the patient. It is recommended to accept the day dose divided into 2 or 3 receptions.

In hypostases in chronic kidney disease should titrate carefully a dose for ensuring gradual initial loss of liquid. It means introduction of such dose which leads to day degrowth of a body approximately on 2 kg for adult patients (about 280 mmol of Na ⁺ ). The recommended initial daily dose for intake makes 40–80 mg. In case of need it is possible to adjust a dose depending on the therapeutic answer of the patient. The general daily dose can be appointed at a time or be divided into 2 receptions. For the patients who are on a hemodialysis, the general daily oral dose makes 250–1500 mg.

to

At OPN before beginning furosemide use, it is necessary to compensate a hypovolemia, hypotension and an essential electrolytic and acid-base imbalance. It is recommended to carry out as soon as possible transition from in/in introductions on oral administration.

In hypostases at a nephrotic syndrome the recommended initial dose for intake makes 40–80 mg/days. In case of need it is possible to regulate a dose depending on the therapeutic answer of the patient. The general daily dose can be appointed at a time or be divided into several receptions.

In hypostases in diseases of a liver of Furosemid-Darnitsa is appointed as addition to therapy by antagonists of Aldosteronum when use is only not enough antagonists of Aldosteronum. For prevention of complications, such as orthostatic hypotension or disturbances of electrolytic and acid-base balance, the dose should be titrated carefully to provide gradual initial loss of liquid. It means purpose of such dose which leads to day degrowth of a body approximately on 0.5 kg for adult patients. The recommended initial daily oral dose makes 40–80 mg. In case of need it is possible to regulate a dose depending on the therapeutic answer of the patient. It is possible to appoint a daily dose once or to divide into several receptions.

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Drug in this dosage form to appoint to children with body weight 10 kg. For children the recommended furosemide dose for oral administration makes 2 mg/kg of body weight, but the maximum daily dose should not exceed 40 mg.

Solution for injections. The mode of use is set by the doctor individually depending on expressiveness of disturbances of water and electrolytic balance, size of glomerular filtration, weight of a condition of the patient. In the course of use of medicine it is necessary to adjust indicators of water and electrolytic balance taking into account a diuresis and dynamics of the general condition of the patient.

Furosemide is appointed in/in only when intake is inexpedient or inefficient (for example at disturbance of absorption in intestines) or in case of need fast effect. At use in/in therapy faster transition to intake of medicine for oral administration is recommended.

For achievement of optimum efficiency and oppression of counter regulation in general is given preference of continuous infusion of furosemide in comparison with repeated bolyusny injections.

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In cases when continuous infusion of furosemide is inexpedient for further treatment after introduction of one or several bolyusny doses, gives preference to the further scheme of treatment with purpose of low doses which are entered through short time intervals (about 4 h), in comparison with high bolyusny doses which are entered through wide intervals of time.

For adults the recommended maximum daily dose of furosemide — 1500 mg.

For children the recommended furosemide dose for parenteral administration makes 1 mg/kg of body weight, but the maximum daily dose should not exceed 20 mg.

Special recommendations about a dosage. The dosage for adults in general is based on use of the recommendations below.

Hypostases in chronic stagnant heart failure. The recommended initial medicament dose makes 20–50 mg/days. In case of need it is possible to adjust a dose according to the therapeutic answer of the patient. It is recommended to accept the daily dose distributed on 2 or 3 receptions.

Hypostases in acute stagnant heart failure. The recommended initial medicament dose makes 20–40 mg/days and is appointed in the form of a bolyusny injection. In case of need it is possible to adjust a dose proceeding from the therapeutic answer of the patient.

Hypostases in chronic kidney disease. Natriuretic effect of furosemide depends on a certain quantity of factors, including severity of a renal failure and balance of sodium. Thus, it is impossible to predict efficiency of a dose precisely. Patients with chronic kidney disease should titrate carefully a dose for ensuring gradual initial loss of liquid. It means use of such dose which leads to daily degrowth of a body approximately on 2 kg for adult patients (about 280 mmol of Na ⁺ ).

a dose of furosemide can be determined by

In a case in/in introductions as follows: treatment begins with introduction continuous in/in infusion of 0.1 mg within 1 min., then the rate of administering of infusion increases everyone half an hour depending on the answer of the patient.

should compensate to

At OPN before use of furosemide a hypovolemia, hypotension and a significant electrolytic and acid-base imbalance.

Is recommended to be turned with

as soon as possible from in into introductions to oral administration.

Recommended initial dose makes 40 mg and is appointed in a look in/in an injection. If purpose of this dose does not lead to desirable increase in removal of liquid, it is possible to appoint furosemide in the form of continuous in/in infusion, since introduction of 50-100 mg of medicine for 1 h

Hypostases in liver diseases. Furosemide is appointed as addition to therapy by antagonists of Aldosteronum when use is only not enough antagonists of Aldosteronum. For prevention of complications, such as orthostatic hypotension or disturbance of electrolytic and acid-base balance, the dose should be titrated carefully to provide gradual initial loss of liquid. It means introduction of such dose which leads to daily degrowth of a body approximately on 0.5 kg for adult patients. If in/in introduction is absolutely necessary, the initial single dose makes 20–40 mg.

Hypertensive crisis. The recommended initial dose of 20-40 mg is appointed in a look in in a bolyusny injection. In case of need it is possible to adjust a dose depending on the therapeutic answer of the patient.

Support of an artificial diuresis in case of poisoning. Furosemide is appointed in/in in addition to introduction of infusions of electrolytic solutions. The dose depends on the therapeutic answer to furosemide. Loss of liquid and electrolytes should be adjusted during initiation and during treatment. In case of poisoning with acid or alkaline substances the removal of liquid can be accelerated by alkalization or oxidation of urine respectively.

Recommended initial dose makes 20–40 mg and is appointed in / century

Special recommendations about use

In/in injection/infusion: in a case in/in introductions it is necessary to appoint furosemide in the form of a slow injection or infusion with a speed no more than 4 mg in 1 min. To patients with the profound abnormal liver functions (creatinine in blood plasma of 5 mg/dl) the injection is recommended to carry out infusion with a speed no more than 2.5 mg in 1 min.

In oil: prescription of medicine in the form of an injection in oil should be limited only exceptional cases when are inexpedient intake and in/in introduction. It is necessary to consider that the medicine method of administration in the form of an injection in oil is not shown for treatment of acute conditions, such as fluid lungs.

Infusion of Furosemid-Darnitsa medicine should not be carried out together with other medicines!

Furosemid-Darnitsa is represented by solution with level rn 8.8-9.8 that has no buffer tank. Thus, active component can drop out in a deposit at values of level rn 7. In case of cultivation of this solution it is necessary to pay attention to providing rn the diluted solution ranging from alkalescent to neutral.

0.9% solution of sodium of chloride can be applied as solvent. It is recommended to apply the diluted solutions as soon as possible.

Contraindication

Hypersensitivity to the furosemide or other components which are a part of medicine. at patients with an allergy to streptocides (for example on sulphonamide antibiotics or sulphonylurea) the cross sensitivity to furosemide can be shown.

Hypovolemia or dehydration of an organism.

Renal failure in the form of an anury if the therapeutic answer to furosemide is not revealed.

Renal failure owing to poisoning with nefrotoksichny or gepatotoksichny medicines.

Heavy hypopotassemia.

Heavy hyponatremia.

Prekomatozny or coma states which are associated with hepatic encephalopathy.

Side effects

from organs of hearing and a vestibular mechanism: the hearing disorder which is usually passing especially at patients with a renal failure, a hypoproteinemia (for example at a nephrotic syndrome) and/or in case of furosemide, too fast in/in introductions. it was reported about deafness cases, sometimes irreversible, after oral administration or administration of furosemide. a ring in ears.

from digestive system: nausea, vomiting, diarrhea, acute pancreatitis.

from a liver and biliary tract: cholestasia, increase in levels of transaminases.

from kidneys and an urinary system: tubulo-interstitial nephrite, increase in volume of urine, increase in level of sodium in urine, increase in level of chlorine in urine, an ischuria (at patients with partial obstruction of outflow of urine), a nephrocalcinosis/nephrolithiasis at premature babies, a renal failure.

from a metabolism, metabolism: disturbances of electrolytic balance (including with clinical manifestations), dehydration and a hypovolemia, especially at patients of advanced age, the hyponatremia, a hypochloraemia, a hypopotassemia, a hypocalcemia, a hypomagnesiemia, a metabolic alkalosis, increase in the TG, XC level, creatinine, uric acid in blood, gout attacks, increase in level of urea in blood, decrease in tolerance to glucose, can pass a course of diabetes from a latent form into expressed, the Barter pseudo-syndrome against the background of the wrong and/or prolonged use of furosemide.

from nervous system: paresthesias, hepatic encephalopathy at patients with hepatocellular insufficiency.

from a cardiovascular system: hypotension, including orthostatic, vasculitis, thrombosis.

from blood and lymphatic system: haemo concentration, thrombocytopenia, leukopenia, eosinophilia, agranulocytosis, aplastic or hemolytic anemia.

from the immune system: heavy anaphylactic and anaphylactoid reactions (in particular, followed by shock).

from skin and hypodermic cellulose: an itching, urticaria, rash, bullous dermatitis, a multiformny erythema, pemphigoid, exfoliative dermatitis, a purpura, reactions of photosensitivity, Stephens's syndrome — Johnson, a toxic epidermal necrolysis, sharp generalizirovanny exanthematous pustulez and DRESS syndrome (a medicamentous rash with an eosinophilia and system symptomatology).

General disturbances and reactions in the injection site: fervescence, local reactions, for example, pain after an injection.

Congenital and inherited/genetic disorders: the increased risk of a patent ductus arteriosus if to appoint furosemide to premature babies during the first days of life.

Special instructions during treatment by furosemide needs to provide to

with

continuous outflow of urine. patients with partial obstruction of outflow of urine require close attention, especially at the initial stages of treatment.

Treatment using furosemide demands regular medical observation. Especially careful monitoring is necessary:

— patients with arterial hypotension;

— the patients getting into group of extra risk owing to considerable decrease in the ABP, for example patients with the profound stenosis of the coronary arteries or blood vessels feeding a brain;

— patients with the latent or expressed form of diabetes;

— patients with gout;

— patients with a gepatorenalny syndrome, that is with a functional renal failure which is associated with a serious illness of a liver;

— patients with a hypoproteinemia which is associated with a nephrotic syndrome (the effect of furosemide can be weakened along with ototoxicity potentiation). Careful titration of a dose is necessary;

— premature babies (development of a nephrocalcinosis/nephrolithiasis is possible); monitoring of function of kidneys and USI of kidneys are required.

Regular monitoring of sodium, potassium and creatinine in blood plasma is recommended to

during therapy by furosemide. Especially careful monitoring is required to patients of group of high risk of development of electrolytic imbalances or in case of considerable additional loss of liquid (for example as a result of vomiting, diarrhea or intensive discharge of sweat). The hypovolemia or dehydration of an organism and also any significant disturbances of electrolytic and acid-base balance should be modified. For this purpose the temporary termination of therapy by furosemide can be required.

development of disturbances of electrolytic balance is influenced by such factors as the existing diseases (for example cirrhosis, heart failure), simultaneous use of medicines and food. For example, as a result of vomiting or diarrhea there can be a lack of potassium.

At use of furosemide it is reasonable to p to recommend to the patient to eat food with the high content of potassium (baked potatoes, bananas, tomatoes, spinach, dried fruits). It is necessary to remember that at use of furosemide there can be a need for medicamentous compensation of deficiency of potassium.

Simultaneous use with risperidony. In placebo - controlled researches of a risperidon with the assistance of patients of advanced age with weak-mindedness higher level of lethality was observed at the patients receiving at the same time furosemide and risperidon in comparison with the patients receiving only risperidon or only furosemide.

Should be careful and to carefully weigh risks and advantage before making the decision on use of such combination or simultaneous treatment using other powerful diuretics. It is necessary to avoid dehydration.

Drug contains lactose therefore to patients with rare hereditary intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is not necessary to apply this medicine.

Use during pregnancy and feeding by a breast. Pregnancy. Furosemide gets through a placental barrier. It is not necessary to appoint it during pregnancy.

feeding Period breast. Furosemide gets into breast milk and can suppress a lactation. Women should stop feeding by a breast during treatment by furosemide.

Children. For children the dose needs to be reduced according to body weight (see USE).

For children who cannot take a dosage form for oral administration, for example, premature and newborn, it is necessary to consider the possibility of use of a form for parenteral administration.

Ability to influence speed of response at control of vehicles or other mechanisms. Some side effects (for example unexpected considerable decrease in the ABP) can break ability of the patient to concentration of attention and speed of its reaction therefore for treatment it is necessary to refrain from control of vehicles or work with mechanisms.

Interaction

Combination which are not recommended. in some cases intake of furosemide during 24 h after Chlorali hydras can cause inflows, the increased sweating, the excited state, nausea, increase hell and tachycardia. therefore simultaneous use of furosemide and Chlorali hydras is not recommended.

Furosemide can increase ototoxicity of aminoglycosides and other ototoksichny medicines. As it can lead to the damage having irreversible character, these medicines should not be applied along with furosemide.

Combination, the demanding uses of preventive measures. In case of simultaneous use of Cisplatinum and furosemide there is a risk of emergence of ototoksichny effects. Besides, nephrotoxicity of Cisplatinum can amplify if furosemide do not appoint in low doses (for example 40 mg to patients with normal function of kidneys) and positive balance of liquid when medicine is applied to achievement of effect of an artificial diuresis during therapy by Cisplatinum.

Furosemide reduces removal of salts of lithium and can lead to increase in level of lithium in blood plasma what the increased risk of toxicity of lithium, including higher risk of emergence of cardiotoxic and neurotoxic effects of lithium is result of. Thus, it is recommended to carry out careful monitoring of level of lithium at the patients receiving this combination therapy.

At the patients receiving diuretics can note heavy arterial hypotension and deterioration in function of kidneys, including cases of a renal failure, especially at the first use of APF inhibitor or the antagonist of a receptor of angiotensin II, or at the first use of these medicines in the raised dose. It is necessary to decide whether it is necessary to stop temporarily furosemide use, or at least to lower a furosemide dose in 3 days prior to treatment, to raise a dose of APF inhibitor or the antagonist of a receptor of angiotensin II.

Risperidon: it is necessary to be careful and to carefully weigh risk and advantage before making decision on performing combination therapy or simultaneous use with furosemide or other powerful diuretics.

Combination which should be applied with care. Simultaneous use of NPVP, including acetylsalicylic acid, can reduce expressiveness of effect of furosemide. At patients with dehydration of an organism or a hypovolemia of NPVP can lead to an acute heart failure. Under the influence of furosemide the toxicity of salicylate can increase.

Decrease in efficiency of furosemide can arise after the combined use with Phenytoinum.

Use of corticosteroids, a karbenoksolona, a licorice root in high doses and prolonged use of depletive can increase risk of development of a hypopotassemia.

Some disturbances of electrolytic balance (such as hypopotassemia, hypomagnesiemia) can increase toxicity of some other medicines (for example the medicaments of a digitalis and medicines causing a syndrome of lengthening of an interval of Q-T).

If the antihypertensive medicines, diuretics or other medicines having property to lower the arterial blood pressure, to apply along with furosemide has to expect much more still decrease in the ABP.

Probenetsid, the methotrexate and other medicines, such, as well as furosemide, are exposed to considerable canalicular secretion in kidneys, can reduce efficiency of furosemide. To the contrary, furosemide can reduce discharge of these medicines kidneys. Performing treatment using high doses (in particular both furosemide, and other medicines) can lead to increase in their levels in serum of blood and risk of development of the side effects caused by furosemide or the performed accompanying therapy.

efficiency of antidiabetic medicines and sympathomimetics which have property to raise the ABP Can decrease (for example epinephrine, Norepinephrinum). Action of kurarepodobny muscle relaxants or theophylline can amplify.

strengthening of harmful effects of nephrotoxic medicines on kidneys Is possible

.

Renal failure can develop at patients who receive therapy by furosemide and high doses of separate cephalosporins.

Simultaneous use of cyclosporine A and furosemide is associated with the increased risk of developing of the gouty arthritis secondary concerning the hyperuricemia caused by furosemide and disturbances of the renal excretion of urates caused by cyclosporine.

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At patients who treat group of high risk of a nephropathy as a result of therapy by radiocontrast substances at treatment by furosemide recorded the big frequency of deterioration in function of kidneys after receiving radiocontrast substances in comparison with that at patients of group of high risk by which carried out only in to hydration before prescribing of radiocontrast substances.

Overdose

Symptoms: the clinical picture of acute or chronic overdose depends mainly on degree and consequences of loss of electrolytes and liquid and includes such signs as a hypovolemia, organism dehydration, haemo concentration, cardiac arrhythmias (including av-blockade and fibrillation of ventricles). thrombosis, nonsense, a flaccid paralysis, apathy and confusion of consciousness belong to symptoms of these disturbances the heavy arterial hypotension (progressing to shock), opn.

Treatment: there are no specific antidotes of furosemide. Therapy is symptomatic.

Storage conditions

In original packing at a temperature not above 25 °C. not to freeze solution for injections.