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

Rapid-acting diuretic, a derivative of sulfonamide. 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.

With heart failure quickly leads to a decrease in preload on the heart through the expansion of large veins.Has hypotensive 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 vasoconstrictor effects, and as a result of a decrease in the volume of circulating blood.

When administered intravenously, furosemide develops after 15 minutes and lasts for 3 hours.

During the period of action, excretion of sodium ions increases significantly, but after its termination, the rate of excretion decreases below the initial level ("rebound" or "cancel" syndrome). 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 time to reach the maximum concentration with intravenous administration is 30 minutes. The relative volume of distribution is 0.1-0.2 l / kg and varies considerably depending on the underlying disease. Furosemide on 98% is associated with blood plasma proteins, mainly with albumins. The final half-life (T1 / 2) of furosemide after intravenous administration is 1 to 1.5 hours.

It is excreted mainly (88%) by the kidneys in unchanged form and mainly by secretion in the proximal tubules.After intravenous administration of furosemide, 60-70% of the administered dose is excreted in this way. Glucuronated furosemide metabolites are 10-20% of the kidney-excreted drug. The rest is excreted through the intestine - 12%. Clearance - 1,5-3 ml / min / kg.

Penetrates through the placental barrier, excreted in breast milk. Its concentration in the fetus and the newborn is the same as that of the mother.

With renal failure, the excretion of furosemide slows down, and T1 / 2 increases; with pronounced renal failure, the final T1 / 2 may increase up to 24 hours.

With hemodialysis and peritoneal dialysis furosemide output is insignificant.

With hepatic insufficiency, T1 / 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. In chronic heart failure, severe degree of arterial hypertension and in elderly patients, excretion of furosemide slows down due to decreased kidney function.

In preterm and full-term children, excretion of furosemide may 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 glucuronurizing ability of the liver is inferior. In children, whose age after conception exceeds 33 weeks, the final T1 / 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.

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 glomerulonephritis, acute renal failure with anuria (glomerular filtration value less than 3-5 ml / min), severe hepatic insufficiency, hepatic coma and precoma, pronounced violations of urinary efflux of any etiology (including unilateral urinary tract damage); pronounced hypokalemia and hyponatremia; hypovolemia (with or without arterial hypotension) or dehydration; decompensated mitral or aortic stenosis, increased central venous pressure (> 10 mm Hg), idiopathic hypertrophic subaortic stenosis, digitalis intoxication.

Carefully:

arterial hypotension; at conditions in which excessive reduction in blood pressure is particularly dangerous (stenotic lesions of the coronary and / or cerebral arteries); with acute myocardial infarction (increased risk of cardiogenic shock); with latent or manifested diabetes mellitus (decreased glucose tolerance); gout; with hepatorenal syndrome; with hypoproteinemia (risk of development of ototoxicity); with a violation of the outflow of urine (benign prostatic hyperplasia,narrowing of the urethra or hydronephrosis); with hearing loss; pancreatitis, diarrhea; at a ventricular arrhythmia in the anamnesis; with systemic lupus erythematosus; in premature infants (the possibility of forming calcium-containing kidney stones (nephrolithiasis) and the deposition of calcium salts in the renal parenchyma (nephrocalcinosis), therefore regular monitoring of kidney function and ultrasound examination of the kidneys is necessary).

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 prescribe intravenously (slowly-jet), if possible - 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 administration of Furosemide is carried out 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 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: excessive reduction in blood pressure (BP), collapse, tachycardia, arrhythmia, a decrease in the volume of circulating blood.

From the central nervous system: dizziness, headache, muscle weakness, cramping calfushc (tetany), paresthesia, apathy, adynamia, weakness, lethargy, drowsiness, confusion, thrombophlebitis.

From the sense organ: hearing impairment.

From the side of the digestive tract: anorexia, dry mouth, thirst, nausea, vomiting, diarrhea, intrahepatic cholestasis, pancreatitis (exacerbation), increased activity of "liver" transaminases.

From the genitourinary system: oliguria, acute urinary retention (in patients with benign prostatic hyperplasia, narrowing of the urethra), interstitial nephritis, hematuria, nephrolithiasis and nephrocalcinosis are possible in preterm infants.

Allergic reactions: purpura, urticaria, exfoliative dermatitis, erythema multiforme, vasculitis, necrotizing angiitis, itching, chills, fever, photosensitivity, anaphylactic shock.

From the hematopoiesis: leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, aplastic or hemolytic anemia.

From the side of water-electrolyte exchange and acid-base balance: hypovolemia, dehydration (risk of thrombosis and thromboembolism), hypokalemia, hyponatremia, hypochloraemia, hypocalcemia, hypomagnesemia, metabolic alkalosis.

Laboratory indicators: hyperglycemia, hypercholesterolemia, hypertriglyceridemia, a transient increase in the concentration of creatinine and urea in the blood, hyperuricaemia, glycosuria, hypercalciuria.

Preterm infants during the first weeks of life furosemide may increase the risk of Botallov duct preservation.

Possible local pain reaction in the place of intramuscular injection.

Overdose:

Symptoms: marked reduction in blood pressure, collapse, shock, hypovolemia, dehydration, hemoconcentration, arrhythmia (including atrioventricular block, ventricular fibrillation), acute renal failure with anuria, thrombosis, thromboembolism, drowsiness, confusion, flaccid paralysis, apathy.

Treatment: correction of violations of water-electrolyte balance and acid-base state, hematocrit, replenishment of circulating blood volume, symptomatic treatment. There is no specific antidote.

Interaction:

Increasing the concentration and the risk of nephrotoxicity and ototoxicity action cephalosporins, aminoglycosides, chloramphenicol, ethacrynic acid, cisplatin,amphotericin B (due to competitive renal excretion).

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

Pressor amines and furosemide mutually reduce efficiency.

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

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

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

Non-steroidal anti-inflammatory drugs, sucralfate reduce the diuretic effect due to inhibition of prostaglandin synthesis, renin level in the blood plasma and aldosterone removal.

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

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

The appointment of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists in patients previously treated with furosemide may lead to impaired renal function, and in some cases, to the development of acute renal failure.

It is recommended that furosemide be canceled, or a decrease in the dose of furosemide 3 days before the start of therapy with ACE inhibitors or angiotensin II receptor antagonists. The simultaneous use of probenicide or methotrexate may decrease the effectiveness of furosemide (the same pathway of secretion). On the other hand furosemide can lead to a decrease in renal elimination of these drugs. Intravenously administered furosemide has a slightly alkaline reaction, so it can not be mixed with drugs with a pH of less than 5.5.

Special instructions:

Before the initiation of Furosemide therapy, one should exclude the presence of pronounced violations of the outflow of urine, including one-sided ones.

Patients with partial impairment of urinary outflow need careful monitoring, especially at the beginning of Furosemide therapy.

In patients with unconsciousness, with benign prostatic hyperplasia, narrowing of the ureters, or hydronephrosis, diuretic control is necessary, in connection with the possibility of acute urinary retention.

On the background of treatment, it is necessary to periodically monitor blood pressure, the content of electrolytes of blood plasma, acid-base state, residual nitrogen, creatinine, uric acid, liver function and, if necessary, appropriate correction of treatment (due to emesis, diarrhea, intense sweating and against parenterally injected liquids), control of excreted urine.

Patients with hypersensitivity to sulfonamides and sulfonylureas may have a "cross" sensitivity to furosemide. Patients receiving high doses of Furosemide, in order to avoid the development of hyponatremia and metabolic alkalosis, it is inappropriate to limit the intake of table salt. For the prevention of hypokalemia, simultaneous administration of potassium and potassium-sparing diuretics is recommendedspironolactone), and also adhere to a diet rich in potassium (lean meat, potatoes, bananas, tomatoes, cauliflower, spinach, dried fruits, etc.).

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 the concentration of plasma electrolytes.

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.

A drug Furosemide should not be mixed in the same syringe with other medicines.

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

Some side effects (eg, excessive blood pressure lowering) can impair the ability to concentrate and respond, which can be dangerous when driving or working with machinery. This especially applies to the period of initiation of therapy or an increase in the dose of the drug, as well as to cases of simultaneous use of antihypertensive drugs or alcohol.

Form release / dosage:

Solution for intravenous and intramuscular injection 10 mg / ml.

Packaging:

2 ml per ampoule of neutral glass. 5 ampoules in a planar cell pack of film and foil, aluminum or without foil.

1 or 2 contour packs together with a scarifier ampoule ceramic or knife for opening ampoules and instructions for use in a pack of cardboard. When using ampoules with a fracture ring or break point, the knife or scarifier is not inserted.

Storage conditions:

Store in a 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000620/10

Date of registration:03.02.2010

The owner of the registration certificate:BINNOFARM, CJSC BINNOFARM, CJSC Russia

Manufacturer: & nbsp

BINNOFARM, CJSC Russia

Representation: & nbspBINNOFARM CJSC BINNOFARM CJSC Russia

Information update date: & nbsp13.11.2015

Illustrated instructions

Instructions

Furosemide (Furosemid)