Furosemide - instructions for use, dose, side effects, contraindications

"Loopback" diuretic; causes a rapidly advancing, strong and short-term diuresis. Has natriuretic and chlororetic effects, increases the excretion of potassium, calcium, magnesium ions. Penetrating into the lumen of the renal tubule in the thick segment of the ascending knee of Henle's loop, blocks the reabsorption of sodium and chlorine ions. Due to the increase in the release of sodium ions, a secondary (osmotically bound water-mediated) enhanced water removal and an increase in the secretion of potassium ions in the distal part of the renal tubule occur.At the same time, the excretion of calcium and magnesium ions increases.

Has secondary effects due to the release of intracellular mediators and redistribution of the intrarenal blood flow. Against the background of course treatment there is no weakening of the effect.

With heart failure quickly leads to a decrease in preload on the heart through the expansion of large veins. It has an antihypertensive effect due to an increase in the excretion of sodium chloride and a decrease in the response of the smooth muscles of the vessels to vasoconstrictive effects and as a result of a decrease in the volume of circulating blood.

The action of furosemide after ingestion occurs in 30-60 minutes, the maximum effect - after 1-2 hours, the duration of the effect - 2-3 hours (with reduced renal function - up to 8 hours).

During the period of action, excretion of sodium ions increases significantly, but after its termination, the rate of excretion decreases below the initial value (the "rebound" or "cancel" syndrome). The phenomenon is caused by a sharp activation of the renin-angiotensin-aldosterone system and other antinatriuretic neurohumoral regulating units in response to massive diuresis; stimulates arginine-vasopressive and sympathetic systems.Reduces the concentration of the atrial natriuretic factor in the blood plasma, causes vasoconstriction. Due to the phenomenon of "bounce" when taken 1 time per day may not have a significant effect on the daily elimination of sodium ions and blood pressure.

Effective in heart failure (both acute and chronic), improves the functional class of heart failure, because reduces the filling pressure of the left ventricle. Reduces peripheral edema, congestion in the lungs, vascular pulmonary resistance, wedging pressure of pulmonary capillaries in the pulmonary artery and right atrial. It is effective at low glomerular filtration rate, therefore it is used to treat hypertension in patients with renal insufficiency.

Pharmacokinetics:

Absorption is high, the maximum concentration is noted in the blood plasma when ingested after 1 hour.

Bioavailability is 60-70%. The relative volume of the distribution is 0.2 l / kg. Communication with blood plasma proteins - 98%. Penetrates through the placental barrier, excreted in breast milk. The liver undergoes biotransformation with the formation of inactive metabolites (mainly - glucuronides).It is secreted into the lumen of the renal tubules through the anion transport system existing in the proximal nephron (by 88%), 12% is excreted through the intestine with bile.

The half-life is 0.5-1 h.

Peculiarities of pharmacokinetics in individual patient groups.

When renal failure the elimination of furosemide slows down, and the half-life increases; with severe renal failure, the final half-life can be increased to 24 hours.

With 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 ambulatory peritoneal dialysis furosemide output is insignificant.

When hepatic insufficiency the half-life of furosemide is increased by 30-90%, mainly due to an increase in the volume of distribution (Vd). Pharmacokinetic parameters in this category of patients can vary greatly.

When heart failure, severe arterial hypertension and in the elderly, the excretion of furosemide is slowed by a decrease in renal function.

Indications:

Ocular syndrome of various genesis, incl. with chronic heart failure, liver cirrhosis (syndrome of portal hypertension); impaired renal function (including nephrotic syndrome); arterial hypertension.

Contraindications:

Hypersensitivity to furosemide, to any of the components of the drug; in patients with hypersensitivity to sulfonamides and sulfo-nil urea derivatives may have cross-sensitivity to furosemide; acute and chronic renal failure with anuria (glomerular filtration value less than 3-5 ml / min), severe hepatic insufficiency, hepatic coma and precoma, acute glomerulonephritis, severe urinary efflux violations of any etiology (including unilateral urinary tract damage), precomatric states, hyperglycemic coma, hyperuricemia, gout,decompensated mitral or aortic stenosis, increased central venous pressure (> 10 mm Hg), hypertrophic obstructive cardiomyopathy, increased central venous pressure (> 10 mm Hg), arterial hypotension, acute myocardial infarction, pancreatitis, hypovolemia and dehydration (with or without arterial hypotension), pronounced hypokalemia, severe hyponatremia, hypochloremia, hypocalcemia, hypomagnesemia, digitalis intoxication, galactose intolerance, lactase deficiency or glucose- alaktoznaya malabsorption, the age of 3 years.

Carefully:

Disorders of urinary outflow (benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis), hypoproteinemia (risk of ototoxicity), arterial hypotension, acute myocardial infarction (increased risk of cardiogenic shock), stenosing coronary and / or cerebral arteries, ventricular arrhythmia in history, systemic lupus erythematosus, pancreatitis, diarrhea, hepatorenal syndrome, diabetes mellitus or a decrease in carbohydrate tolerance, gout.

Pregnancy and lactation:

Furosemide penetrates through the placental barrier, so the drug should not be prescribed during pregnancy. Reception of the drug Furosemide is possible only if the intended benefit to the mother exceeds the potential risk to the fetus, in such cases careful monitoring of the fetus is necessary. During lactation, taking the drug Furosemide contraindicated because furosemide can be excreted in breast milk and suppress lactation.

Dosing and Administration:

The dosage regimen is set individually, depending on the indications, the clinical situation, the age of the patient.

During the treatment, the dosage regimen is adjusted depending on the magnitude of the diuretic response and the dynamics of the patient's condition.

The drug is administered orally, before meals.

Adults: in an initial dose of 20-80 mg; in the absence of a diuretic response, an increase in the dose of 20-40 mg every 6-8 hours is possible until an adequate diuretic response is obtained (large doses are divided into 2-3 doses); a single dose, if necessary, can be increased to 600 mg or more (required with a decrease in glomerular filtration and hypoproteinemia).After reducing edema, the drug is prescribed in smaller doses with a break of 1-2 days.

With arterial hypertension, 20-40 mg is prescribed, in the absence of a sufficient reduction in blood pressure, other antihypertensives should be added to the treatment. When furosemide is added to already prescribed antihypertensive drugs, their dose should be reduced 2 times.

Children from 3 years - at a rate of 1-2 mg / kg per day, with the possible increase to a maximum dose of 6 mg / kg / day, subject to taking the drug no more than 6 hours later.

Side effects:

From the cardiovascular system:

Pronounced decrease in blood pressure, orthostatic hypotension, collapse, tachycardia, arrhythmias.

From the central nervous system:

Paresthesia, hepatic encephalopathy in patients with hepatic insufficiency.

From the sense organs:

Hearing impairment, usually reversible, and / or tinnitus, especially in patients with kidney failure or hypoproteinemia (nephrotic syndrome).

From the digestive system:

Nausea, vomiting, diarrhea, constipation; intrahepatic cholestasis, increased activity of "liver" transaminases, acute pancreatitis.

From the genitourinary system:

Oliguria, acute urinary retention (for example, with prostatic hypertrophy, narrowing of the urethra, hydronephrosis), hematuria, decreased potency, interstitial nephritis.

From the peripheral blood:

Thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia or hemolytic anemia.

From the side of water-electrolyte exchange:

Hyponatremia, hypochloraemia, hypokalemia, hypomagnesemia, hypocalcemia, metabolic alkalosis. Symptoms that indicate the development of violations of the electrolyte and acid-base state can be headache, confusion, convulsions, tetany, muscle weakness, heart rhythm disorders and dyspepsia Expansion.

Hypovolemia (decrease in the volume of circulating blood) and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop thrombosis.

From the side of metabolism:

Hypercholesterolemia, triglyceridemia, a transient increase in creatinine and urea concentrations in the blood plasma, an increase in serum uric acid concentrations, which can cause or exacerbate gout,decrease in glucose tolerance (manifestation of latent diabetes mellitus is possible).

From the skin:

Skin itching, urticaria, other skin rashes or bullous skin lesions, erythema multiforme, bullous pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, purpura, fever, vasculitis, eosinophilia, photosensitivity, severe anaphylactic or anaphylactoid reactions up to shock, which until now have been described only after intravenous administration.

Laboratory indicators: hyperglycemia, hypercholesterolemia, hyperuricemia, glucosuria, hypercalciuria.

Overdose:

Symptoms: marked decrease in arterial pressure, collapse, shock, hypovolemia, dehydration, hemoconcentration, arrhythmias (including AV blockade, fibrillation of the stomachdaughters), acute renal failure with anuria, thrombosis, thromboembolism, drowsiness, confusion, flaccid paralysis, apathy.

Treatment: gastric lavage, reception of activated carbon, correction of water electrolyte balance and acid-base state (CBS), replenishment of the volume of circulating blood,symptomatic treatment, maintenance of vital functions. There is no specific antidote.

Interaction:

Increases the concentration and risk of nephro- and ototoxic effects of cephalosporins, aminoglycosides, chloramphenicol, ethacrynic acid, cisplatinum, amphotericin B (due to competitive renal excretion).

Increases the effectiveness of diazoxide and theophylline, reduces - hypoglycemic drugs, allopurinol.

Reduces renal clearance of lithium preparations and increases the likelihood of development of intoxication.

Strengthens the antihypertensive effect of antihypertensive drugs, neuromuscular blockade caused by depolarizing muscle relaxants (suxamethonium) and weakens the effect of nondepolarizing muscle relaxants.

Pressor amines and furosemide mutually reduce efficiency.

Drugs that block tubular secretion, increase the concentration of furosemide in serum.

With the simultaneous use of glucocorticosteroids, amphotericin B increases the risk of hypokalemia, with cardiac glycosides, the risk of developing digital intoxication due to hypokalemia (for high-and low-polar cardiac glycosides) and elongation of the half-life of the drug (for low-polarity). Non-steroidal anti-inflammatory drugs, sucralfate reduce the diuretic effect of furosemide due to decreased absorption in the gastrointestinal tract, changes in renin concentration in the blood plasma, and aldosterone release.

Phenytoin - reduction of diuretic action of furosemide.

Assigning an angiotensin-converting enzyme (ACE) inhibitors 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 or enhance inhibitors their dose is recommended to cancel furosemide, or reduce its dose.

Probenicid, methotrexate or other drugs that, like furosemide, are secreted in the renal tubules, can reduce the effects of furosemide (the same pathway of kidney secretion), on the other hand furosemide can lead to a decrease in the excretion of these drugs by the kidneys.

Risperidone and furosemide intensify (mutually) antihypertensive effect. In elderly patients with dementia, the combined use of furosemide and risperidone increases the risk of death.

With the simultaneous use of furosemide with angiotensin II receptor antagonists, no clinically relevant interactions were noted.

The intake of salicylates in large doses with furosemide therapy increases the risk of their toxicity (due to competitive renal excretion). Cyclosporin - the risk of developing gouty arthritis due to hyperuricemia caused by furosemide, and cyclosporine disruption of urate excretion by the kidneys.

In patients with a high risk of developing nephropathy for the introduction of radiopaque means, taking furosemide, a higher incidence of renal dysfunction was observed compared with patients at high risk of developing nephropathy for the introduction of radiopaque agents that received only IV hydration prior to the administration of the radiopaque.

Special instructions:

Against the background of course treatment, it is necessary to periodically monitor blood pressure, blood plasma electrolytes (incl.sodium, calcium, potassium, magnesium), acid-base state, concentration of residual nitrogen, creatinine, uric acid, liver function and, if necessary, appropriate treatment correction (more often in patients with frequent vomiting and parenteral fluids).

Patients with hypersensitivity to sulfonamides and sulfonylurea derivatives may have cross-sensitivity to furosemide. Patients receiving high doses of furosemide, in order to avoid the development of hyponatremia and metabolic alkalosis, it is not advisable to limit the intake of table salt.

For the prevention of hypokalemia, the simultaneous administration of potassium and potassium-sparing diuretics (primarily spironolactone) is recommended, as well as adherence to a diet rich in potassium.

The choice of dosage regimen for patients with ascites on the background of cirrhosis of the liver should be carried out under stationary conditions (violations of the water-electrolyte balance may lead to the development of hepatic coma). This category of patients shows regular monitoring of the content of plasma electrolytes.In the presence of ascites without peripheral edema, it is recommended to use in doses that provide an additional diuresis in the volume of no more than 700-900 ml / day in order to avoid the development of oliguria, azotemia and disturbance of the water electrolyte balance. In order to exclude the phenomenon of "bounce" in the treatment of hypertension, appoint at least 2 times a day. It should be borne in mind that prolonged reception can lead to the appearance of weakness, fatigue, lower blood pressure and cardiac output, and excessive diuresis with myocardial infarction with stagnant phenomena in the small circulation can promote the development of cardiogenic shock. It is necessary to temporarily cancel (for several days) before the appointment of angiotensin converting enzyme inhibitors.

When azotemia and oliguria appear or increase in patients with severe progressive kidney disease, it is recommended to suspend treatment.

Patients with diabetes mellitus or with reduced glucose tolerance require periodic monitoring of glucose concentrations in the blood and urine.

In patients unconscious, with prostatic hypertrophy, ureteral narrowing, or hydronephrosis, control of urinary excretion is necessary, in connection with the possibility of acute urinary retention.If oliguria is kept for 24 hours, Furosemide should be discarded.

During the treatment period it is necessary to avoid the employment of potentially hazardous activities requiring increased attention and speed of psychomotor reactions and to exercise caution when driving vehicles.

Form release / dosage:Tablets of 40 mg.

Packaging:

10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil or paper with a polymer coating.

For 50 tablets in a can of polymer type BP or in a bank of dark glass type BTS, Uktheporous plastic cover.

Each jar or 1, 2, 3 or 5 contour squares, together with the instruction for use, is placed in a pack of cardboard.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N000655 / 02

Date of registration:25.01.2012

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Representation: & nbspBIOSINTEZ JSC BIOSINTEZ JSC Russia

Information update date: & nbsp12.11.2015

Illustrated instructions

Instructions

Furosemide (Furosemide)