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

Pharmacodynamics:"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.

During the period of action, excretion of sodium ions increases significantly, but after its termination, the elimination rate decreases below the initial level ("rebound" syndrome, or "cancellation"). The phenomenon is caused by a sharp activation of the renin-angiotensin and other antinatriuretic neurohumoral regulating units in response to massive diuresis.

Pharmacokinetics:

The action of furosemide after intravenous administration occurs in 5-10 minutes; the maximum of action - after 1-2 hours, the duration of the effect - 2-3 hours (with reduced renal function - up to 8 hours) .; stimulates arginine-vasopressive and sympathetic systems.Decreases the level of the atrial natriuretic factor in the plasma, causes vasoconstriction. Due to the phenomenon of "bounce" when taken 1 time per day may not have a significant effect on daily excretion of sodium and blood pressure. Absorption is high, but with severe kidney disease or chronic heart failure, the degree of absorption decreases.

Time to reach the maximum concentration of the drug in the plasma with iv injection - 30 min.

Bioavailability is 60-70%. The relative volume of the distribution is 0.2 l / kg. Connection with plasma proteins - 98 %. Penetrates through the placental barrier, excreted in breast milk. Metabolized in the liver with the formation of 4-chloro-5-sulfamoylantranil. acid. It is secreted into the lumen of the renal tubules through the anion transport system existing in the proximal nephron. The half-life of the drug in patients with normal renal and hepatic function is 0.5-1.5 hours. In anuria, the half-life may increase to 1.5-2.5 hours, with combined renal and hepatic insufficiency up to 11-20 hours.

It is excreted mainly (88%) by the kidneys in unchanged form and in the form of metabolites; with feces - 12%. Clearance - 1,5-3 ml / min / kg.

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. Preserves efficacy at a low glomerular filtration rate, therefore it is used to treat hypertension in patients with renal insufficiency.

Indications:

Edema syndrome with chronic heart failure, edematous syndrome with acute heart failure, edematous syndrome with chronic renal failure, acute renal failure, edematous syndrome with nephrotic syndrome (with a nephrotic syndrome in the foreground is the treatment of the underlying disease); edematous syndrome with liver diseases, cerebral edema; hypertensive crisis; maintenance of forced diuresis in case of poisoning with chemical compounds, excreted kidneys in unchanged form.

Contraindications:

Hypersensitivity to furosemide and other components of the drug; in patients with an allergy to sulfonamides (sulfanilamide antimicrobial agents or sulfonylureas), a "cross" allergy may develop furosemide, acute renal failure with anuria (glomerular filtration rate less than 3-5 ml / min), severe hepatic insufficiency, hepatic coma and precoma, severe urinary efflux violations of any etiology (including unilateral urinary tract damage), acute glomerulonephritis, decompensated mitral or aortic stenosis, pronounced hypokalemia and hyponatremia; hypovolemia (with or without arterial hypotension) or dehydration, increased central venous pressure (> 10 mm Hg), idiopathic hypertrophic subaortic stenosis.

Carefully:

Arterial hypotension, conditions in which excessive reduction in blood pressure is particularly dangerous (stenosing lesions of the coronary and / or cerebral arteries), acute myocardial infarction (increased risk of cardiogenic shock), gout, hepatorenal syndrome,(benign prostatic hyperplasia, narrowing of the urethra or hydronephrosis), systemic lupus erythematosus, hypoproteinemia (risk of ototoxicity development), diabetes mellitus (decreased glucose tolerance), hearing loss, pancreatitis, diarrhea, ventricular arrhythmia in history, preterm infants (the possibility of formation of calcium-containing stones in the kidneys (nephrolithiasis) and the deposition of calcium salts in the renal parenchyma (nephrocalcinosis), therefore regular monitoring of kidney function is necessary lterrazovec study of the kidneys), pregnancy, lactation.

Pregnancy and lactation:

Furosemide penetrates through the placental barrier, so the drug should not be administered during pregnancy. If, for vital reasons, furosemide is prescribed to pregnant women, careful monitoring of the fetus is necessary. Furosemide suppresses lactation. In the lactation period, furosemide is contraindicated.

Dosing and Administration:

Furosemide Assign intravenously (slowly struyno), when impossible - intramuscularly (when intravenous administration or application of the drug inside) is impossible.It is recommended to use the smallest doses of the drug, sufficient to achieve the necessary therapeutic effect. Intravenous furosemide is administered when oral administration of the drug is not possible or there is a violation of absorption of the drug in the small intestine or in urgent situations.

The question of the duration of treatment is decided by the doctor, given the nature and severity of the disease. After the onset of the desired effect, they switch to taking the drug inside.

When administered intravenously, the drug 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 rate of administration does not exceed 2.5 mg per minute.

The drug is administered in doses of 20-40 mg 1-2 times a day; in the absence of a diuretic response every 2 hours, injected in an increased 50% dose until an adequate diuresis is achieved. Patients with reduced glomerular filtration and low diuretic response are prescribed in large doses - 1-1.5 g. In children the initial single dose of the drug is 1 mg / kg (0.1 ml / kg) of body weight slowly for 1-2 minutes (0.5 ml / kg per minute).The maximum daily dose for intravenous administration in children is 6 mg / kg.

Side effects:

From the cardiovascular system: a marked decrease in blood pressure, orthostatic hypotension, collapse, tachycardia, arrhythmias, a decrease in total circulating blood, in premature infants during the first days of life furosemide can increase the risk of conservation Bottalov duct.

From the side of the central nervous system: dizziness, headache, paresthesia, apathy, adynamia, weakness, lethargy, drowsiness, confusion.

From the sense organs: visual and hearing impairments.

On the part of the digestive system: decreased appetite, dryness of the oral mucosa, thirst, nausea, vomiting, constipation or diarrhea, cholestatic jaundice, pancreatitis (exacerbation), increased activity of "liver" transaminases.

On the part of the genitourinary system: oliguria, acute retention of urine (in patients with prostatic hypertrophy), interstitial nephritis, hematuria, transient increase in creatinine and urea concentration, decreased potency.

Allergic reactions: purpura, urticaria, exfoliation dermatitis,multiforme exudative erythema, vasculitis, necrotizing angiitis, itchy skin, bullous skin lesions, chills, fever, photosensitivity, toxic epidermal necrolysis, Stevens-Johnson syndrome, anaphylactic shock.

On the part of the hematopoiesis: leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia, aplastic anemia or hemolytic anemia, hypertriglyceridemia.

On the part of water-electrolyte metabolism: hypovolemia, dehydration (risk of thrombosis and thromboembolism), hypokalemia, hyponatremia, hypochloraemia, hypocalcemia, hypomagnesemia, metabolic alkalosis. Other: muscle weakness, spasms of gastrocnemius muscles (tetany). Laboratory indicators: hyperglycemia, hypercholesterolemia, hyperuricemia, glucosuria, hypercalciuria.

With intravenous administration (in addition) - thrombophlebitis, calcification of kidneys in premature infants.

With intramuscular injection (optional) - soreness in the injection site.

Overdose:

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

Treatment: correction of water-electrolyte balance and acid-base state, replenishment of circulating blood volume, symptomatic treatment. 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.

When used simultaneously with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, the antihypertensive effect is enhanced. Possible severe arterial hypotension, especially after taking the first dose of furosemide, apparently due to hypovolemia,which leads to a transient enhancement of the hypotensive effect of ACE inhibitors. Increased risk of renal dysfunction and the development of hypokalemia is not ruled out.

With simultaneous use with phenytoin, the diuretic effect of furosemide is significantly reduced.

With simultaneous application with probenecid, the renal clearance of furosemide decreases.

After intravenous administration of furosemide against the background of chloral hydrate therapy, it is possible to increase sweating, heat, unstable arterial pressure, tachycardia.

You should be careful when using furosemide with methotrexate, as tubular secretion is reduced.

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

It intensifies the neuromuscular blockade caused by depolarizing muscle relaxants (suxamethonium) and weakens the effect of nondepolarizing muscle relaxants (tubocurarine).

Pressor amines and furosemide mutually reduce efficiency.

With the simultaneous use of glycocorticoid agents, amphotericin B increases the risk of hypokalemia,with cardiac glycosides increases the risk of digitalis intoxication due hypokalemia (for high and low polarity cardiac glycosides) and lengthening the half-life of the drug (for low polarity). Non-steroidal anti-inflammatory drugs, sucralfate reduce diuretic effect due to inhibition of synthesis Pg, changes in plasma renin concentrations and the release of aldosterone.

The intake of salicylates in large doses with furosemide therapy increases the risk of their toxicity (due to competitive renal excretion).

Cyclosporin A - the risk of gouty arthritis due to hyperuricemia caused by furosemide, and violations of cyclosporine withdrawal of urate by the kidneys.

In patients with a high risk of developing nephropathy for the introduction of radiopaque agents that received furosemide, There was a higher incidence of renal impairment as compared to patients with high risk of nephropathy for administering contrast media, who received only in / hydration prior to introducing the radiopaque agent.

Intravenously administered furosemide has a slightly alkaline reaction, so it should not be mixed with drugs with a pH of less than 5.5.

Special instructions:

On the background of treatment, it is necessary to periodically monitor blood pressure, blood plasma electrolytes, acid-base state, residual nitrogen, creatinine and uric acid concentration, liver function and, if necessary, appropriate correction of treatment (due to vomiting, diarrhea, intense sweating and against the background parenterally injected fluids), control of excreted urine, Patients receiving high doses of furosemide, in order to avoid the development of hyponatremia and metabolic alkalosis, it is inappropriate limit the intake of table salt.

Before the initiation of furosemide therapy, one must exclude the presence of severe abnormalities of urine outflow, including one-sided ones. Patients with partial impairment of urinary outflow need careful monitoring, especially at the beginning of furosemide therapy. A drug furosemide should not be mixed in the same syringe with other medicines.

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

Increased risk of development of violations of water-electrolyte balance is observed in patients with renal insufficiency.

Selection of the dosing regimen for patients with ascites against the background of cirrhosis of the liver should be done in a stationary setting (violations of the water-electrolyte balance may lead to the development of the hepatic coma). This category of patients shows regular monitoring of electrolytes in plasma.

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

In patients with diabetes mellitus or with reduced glucose tolerance, periodic monitoring of glucose concentrations in the blood and urine is required.

In patients with unconsciousness, prostatic hypertrophy, narrowing of the ureters, or hydronephrosis, monitoring of urination is necessary in connection with the possibility of acute urinary retention.

Preterm infants require regular monitoring of kidney function and ultrasound of the kidneys (the possibility of nephrolithiasis and nephrocalcinosis).

During the treatment period, avoidance of potentially hazardous activities, such as driving and handling,requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection 10 mg / ml. 2 ml of the drug into neutral glass ampoules.

Packaging:

5 ampoules are placed in a contiguous cell pack of a polyvinylchloride film without coating.

1 or 2 contour mesh packages are placed in a pack of cardboard for consumer containers.

5.10 ampoules are placed in a pack of cardboard for consumer containers with partitions or grilles, or a paperboard separator for consumer packaging or sack paper.

10 ampoules are placed in a box of cardboard for consumer packaging with a pile of paper paste. The box is pasted with a label-parcel of paper label or coated. Each instruction pack or box is supplied with instructions for use, an ampoule knife or ampoule scarifier.

When using ampoules with incisions, break rings or break points, the ampoule opener or ampoule ampoule opener is not inserted.

Storage conditions:

In a place protected from light and inaccessible to children at a temperature of no higher than 25 ° C.

Shelf life:2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N003668 / 01

Date of registration:16.07.2009

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Representation: & nbspBIOCHEMICAL JSC BIOCHEMICAL JSC Russia

Information update date: & nbsp13.11.2015

Illustrated instructions

Instructions

Furosemide (Furosemide)