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

Furosemide - "Loop" diuretic; causes a rapidly advancing, strong and short-term diuresis. Has natriuretic and chlororetic effects, increases the excretion of potassium ions (K +), calcium (Ca2 +), magnesium (Mg2 +). 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 ions (Na +) and chlorine (Cl). Due to the increased allocation Na + secondary (mediated by osmotically bound water) secondary water elimination and an increase in K + secretion in the distal part of the renal tubule occurs. At the same time, the excretion of Ca2 + and Mg2 +.

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. Has hypotensive effectas a result of an increase in the excretion of sodium chloride (NaCl) and reduce the reaction smooth musculature vessels for vasoconstrictor effects, and as a result of a decrease in the volume of circulating blood (BCC). The action of furosemide after ingestion occurs in 30-60 minutes, the maximum of action is 1 to 2 hours, the duration of the effect is 2 to 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 elimination decreases below the initial value ("rebound" syndrome, or "cancellation"). The phenomenon is caused by a sharp activation of the renin-angiotensin-aldosterone system (RAAS) 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 daily excretion Na + and blood pressure.

Pharmacokinetics:

Absorption is high, bioavailability is 60-70%. The time to reach the maximum concentration for ingestion (TCmax) - 1-2 hours. The relative volume of the distribution is 0.2 l / kg of body weight. Communication with blood plasma proteins - 98%. Penetrates through the placental barrier, excreted in breast milk. Clearance is 1.5-3 ml / min / kg.

Metabolized in the liver with the formation of 4-chloro-5-sulfamoylantranilic acid. It is secreted into the lumen of the renal tubules through the anion transport system existing in the proximal nephron. The half-life (T1/2) - 0.5-1 h. It is excreted mainly (88%) by the kidneys in unchanged form and in the form of metabolites; through the intestine - 12%.

With renal failure, the excretion of furosemide slows down, and the half-life increases; with severe renal failure, the final half-life can increase up to 24 hours.

With hemodialysis and peritoneal dialysis and permanent ambulatory peritoneal dialysis furosemide output is insignificant.

In liver failure, the half-life of furosemide is increased by 30 - 90%, mainly due to the increase in the volume of distribution. The pharmacokinetics in such patients is variable.

With heart failure, severe degree of arterial hypertension and in elderly patients, excretion of furosemide slows down due to a decrease in kidney function.

Indications:

Ocular syndrome of various genesis, incl. with chronic heart failure, liver cirrhosis (syndrome of portal hypertension); edematous syndrome of renal genesis (with nephrotic syndrome in the foreground is the treatment of the underlying disease); arterial hypertension.

Contraindications:

Hypersensitivity to furosemide or to any of the components of the drug; patients with allergies to sulfonamides (sulfonamide antimicrobial agents or sulfonylureas) may have a cross-allergy to furosemide. Acute renal failure with anuria (glomerular filtration value less than 3-5 ml / min), severe hepatic impairment, hepatic coma and precoma,severe abnormalities in urinary efflux of any etiology (including unilateral urinary tract damage), acute glomerulonephritis, hyperglycemic coma, hyperuricemia, decompensated mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy (GOKMP); increased central venous pressure (> 10 mm Hg), hypovolemia and dehydration (with or without arterial hypotension), pronounced hypokalemia, expressed. hyponatremia, hypochloraemia, hypocalcemia, hapomagniemia, digitalis intoxication; pregnancy, lactation, children under 3 years (solid dosage form).

Carefully:

Disorders of urinary outflow (benign prostatic hyperplasia, narrowing of the urethra), systemic lupus erythematosus, hypoproteinemia (risk of ototoxicity development), diabetes mellitus (decreased glucose tolerance), stenosing cerebral artery atherosclerosis, gout, arterial hypotension, acute myocardial infarction, pancreatitis, hepatorenal syndrome, diarrhea, ventricular arrhythmia in the anamnesis.

Pregnancy and lactation:

During pregnancy, Furosemide is not recommended, since Furosemide penetrates the placental barrier. If according to the vital indications the drug is prescribed to pregnant women, careful monitoring of the fetal condition is necessary.

In the period of breastfeeding, Furosemide is not recommended. Furosemide suppresses lactation. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The dosage regimen is set individually, depending on the indications, the clinical situation, the patient's age, the magnitude of the diuretic response and the dynamics of the patient's condition.

The duration of therapy is determined by the doctor individually.

It is recommended to use the smallest doses, sufficient to achieve the necessary therapeutic effect.

The drug is prescribed by mouth, in the morning, before meals, the average single initial dose for adults is 20-80 mg (1 / 2-2 tablets). In the absence of a diuretic response, the dose is increased by 20-40 mg every 6-8 hours until an adequate diuretic response is obtained. It is recommended that the daily dose be divided into 2-3 doses.A single dose, if necessary, may be increased to 600 mg or more (required with a decrease in glomerular filtration and hypoproteinemia).

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

The maximum daily dose is 1500 mg.

After reducing edema, the drug is prescribed in smaller doses with a break of 1-2 days.

The initial single dose in children is 1-2 mg / kg of body weight per day, maximum 6 mg / kg / day, subject to taking the drug no more than 6 hours later.

Side effects:

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 disturbances and dyspeptic disorders.

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 cardiovascular system: a marked decrease in blood pressure, orthostatic hypotension, collapse, tachycardia, arrhythmias.

On the part of the metabolism: hypercholesterolemia, triglyceridemia, a transient increase in the concentrations of creatinine and urea in the blood plasma, an increase in serum uric acid concentrations, which can cause or intensify the manifestations of gout, a decrease in glucose tolerance (manifestation of latent diabetes mellitus).

On the part of the genitourinary system: oliguria, acute urinary retention (for example, with prostatic hypertrophy, narrowing of the urethra, hydronephrosis), hematuria, decreased potency, interstitial nephritis.

On the part of the digestive system: nausea, vomiting, diarrhea, constipation; intrahepatic cholestasis, increased activity of "liver" transaminases, acute pancreatitis. .

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 renal insufficiency or hypoproteinemia (nephrotic syndrome).

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.

From the peripheral blood: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia or hemolytic anemia.

Overdose:

Symptoms: severe decrease in arterial pressure, collapse, shock, hypovolemia, dehydration, hemoconcentration, arrhythmias (including atrioventricular block, ventricular fibrillation), acute, renal failure with anuria, thrombosis, thromboembolism, drowsiness, confusion, flaccid paralysis, apathy.

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

Interaction:

When used simultaneously with phenobarbital and phenytoin the action of furosemide decreases.

Increases concentration and risk of nephro- and ototoxic action cephalospores, aminoglycosides, chloramphenicol, ethacrynic acid, cystatin, amphotericin B (due to competitive renal excretion).

Increases efficiency diazoxide and theophylline, reduces - hypoglycemic drugs, allopurinol.

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

Pressor amines and furosemide mutually reduce efficiency.

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

With simultaneous application glucocorticosteroids, amphotericin B increased risk of hypokalemia, with cardiac glycosides - the risk of developing digitalis intoxication due to hypokalemia increases (for high- and low-polar cardiac glycosides) and elongation of the half-life (for low-polarity).

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the diuretic effect due to inhibition of prostaglandin synthesis, changes in renin concentration in the blood plasma, and aldosterone release.

Sucralfate reduces the absorption of furosemide and weakens its effect (these drugs should be taken at intervals of at least 2 hours).

Simultaneous reception of large doses salicylates on the background of furosemide therapy increases the risk of their toxicity (due to competitive renal excretion).

Appointment inhibitors of angiotensin-converting enzyme, (ACE) patients previously treated with furosemide may lead to an excessive decrease; arterial pressure with impaired renal function, and in some cases to the development of acute renal failure, therefore, three days before the start of treatment with ACE inhibitors or increasing their doses, it is recommended that furosemide be canceled,or a decrease in its dose.

Probenicide, methotrexate and other medications that, like furosemide, are secreted in the renal tubules, can reduce the action 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.

Lithium salts - under the influence of furosemide, lithium excretion decreases, which increases the serum concentration of lithium and increases the risk of toxic effects of lithium, including its damaging effects on the heart and nervous system. Therefore, when using this combination, control of serum lithium concentrations is required.

Cyclosporin - risk of gouty arthritis due to hyperuricemia caused by furosemide, and cyclosporine disruption of urate excretion by the kidneys.

In patients with a high level of development of nephropathy for the introduction radiocontrast agents, who took furosemide, a higher incidence of renal dysfunction was observed compared to patients at high risk of developing nephropathy for administration radiocontrast agents, who received only intravenous hydration prior to administration radiopaque means.

Special instructions:

Against the background of course treatment, it is necessary to periodically monitor blood pressure, the content of plasma electrolytes (incl. Na +, Ca2 +, K +, Mg2+), acid-base state, residual nitrogen, creatinine, uric acid, liver function and, if necessary, appropriate correction of treatment (with a higher multiplicity in patients with frequent vomiting and against parenterally injected fluids).

Furosemide can lead to a transient increase in the level of creatinine. An increase in the level of uric acid in the serum under the influence of furosemide can cause attacks of gout.

Patients with hypersensitivity to sulfonamides and sulfonylureas 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.An increased risk of developing water-electrolyte imbalance is noted in patients with renal insufficiency. 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. 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.

Effect on the ability to drive transp. cf. and fur:

During the treatment period it is necessary to avoid practicing potentially dangerous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Tablets of 40 mg.

Packaging:

For 10 tablets in a contour mesh package made of a light-protective PVC film and aluminum foil. 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In a dry, dark place at a temperature of 2 to 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N000193 / 01

Date of registration:22.12.2011

The owner of the registration certificate:MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC Russia

Manufacturer: & nbsp

MOSHIMFARM PREPARATES them. NA Semashko OJSC Russia

Representation: & nbspMOSHIMFARM PREPARATES them. NA Semashko OJSC MOSHIMFARM PREPARATES them. NA Semashko OJSC Russia

Information update date: & nbsp12.11.2015

Illustrated instructions

Instructions

Furosemide (Furosemide)