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 release and an increase in the secretion of potassium ions in the distal part of the renal tubule occurs. Simultaneously, the release 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 rapidly reduces preload (by expanding the veins), reduces pulmonary artery pressure and the filling pressure of the left ventricle. This rapidly developing effect appears to be mediated through the effects of prostaglandins and therefore the condition for its development is the absence of disturbances in the synthesis of prostaglandins, in addition to which this effect also requires sufficient preservation of the renal function.

Has hypotensive effect due to an increase in the elimination 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 (BCC).

The action of furosemide after ingestion occurs in 30-60 minutes, the maximum of action is 1-2 hours, the duration of the effect is 3-6 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" 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; stimulates the arginine-vasopressive and sympathetic system. Reduces the level of the atrial natriuretic factor in the blood plasma, causes vasoconstriction. Due to the phenomenon of "ricochet" when taken once a day furosemide may not have a significant effect on the daily excretion of sodium ions and blood pressure.

Pharmacokinetics:

Absorption - high, bioavailability - 50-70%. The time to reach the maximum concentration with oral administration is 1-1.5 hours. The relative volume of distribution is 0.1-0.2 l / kg body weight. Communication with plasma proteins is 98% (mainly with albumins). Penetrates through the placental barrier, excreted in breast milk. Clearance - 1,5-3 ml / min / kg.

Metabolized to form 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. Half-life is 0.5-1 hour. 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 an 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 decreased 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; in patients with allergies to sulfonamides (sulfonamideantimicrobial agents or sulfonylureas) there may be a cross-allergy to furosemide;

renal failure with anuria;
hepatic coma and precoma;
pronounced hypokalemia;
severe hyponatremia;
hypovolemia (with or without arterial hypotension) or dehydration;
marked abnormalities of urine outflow from any etiology (including unilateral urinary tract damage);
digitalis intoxication;
acute glomerulonephritis;
uncompensated aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy;
increased central venous pressure (> 10 mm Hg);
hyperuricemia;

age up to 3 years (solid dosage form);
lactation period.
intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption.

Carefully:

arterial hypotension, stenosing arteriosclerosis of cerebral arteries, hypoproteinemia (risk of ototoxicity development), disturbances of urine outflow (prostatic hyperplasia, narrowing of the urethra or hydronephrosis), systemic lupus erythematosus, ventricular arrhythmia in the anamnesis,acute myocardial infarction (increased risk of developing cardiogenic shock), diarrhea, pancreatitis, diabetes mellitus (decreased glucose tolerance), hepatorenal syndrome, gout, pregnancy (especially the first half, it is possible to use only for life indications).

Pregnancy and lactation:

Furosemide penetrates the placental barrier, so it should not be administered during pregnancy. If according to the vital indications the drug is prescribed to pregnant women, careful monitoring of the fetal condition is necessary.

During the period of breastfeeding, furosemide is contraindicated. Furosemide suppresses lactation. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Assign inside, in the morning, on an empty stomach, without chewing and washing down with a sufficient amount of liquid.

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

The duration of therapy is determined by the doctor individually.

The average single initial dose for adults is 20-80 mg; 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. Single dose, if necessary, can be increased to 600 mg or more (required with a decrease in the value of glomerular filtration and hypoproteinemia).

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

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

Side effects:

From the side of water-electrolyte and acid-base balance:

- 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 and dehydration (more often in elderly patients), which can lead to hemoconcentration with a tendency to develop thrombosis.

From the cardiovascular system:

- excessive reduction of blood pressure, orthostatic hypotension, collapse, tachycardia, arrhythmias, decrease in the volume of circulating blood.

From the side of metabolism:

- hypercholesterolemia, hypertriglyceridemia

- a transient increase in the concentration of creatinine and urea in the blood,

- increased serum uric acid concentrations, which can cause or exacerbate gout,

- a decrease in glucose tolerance (possible manifestation of latent diabetes mellitus).

From the urinary system:

- Oliguria, acute retention of urine (for example, with prostatic hyperplasia, narrowing of the urethra, hydronephrosis); interstitial nephritis, hematuria, decreased potency.

From the digestive tract:

- rarely - nausea, vomiting, diarrhea, isolated cases of intrahepatic cholestasis, increased activity of "liver" enzymes, acute pancreatitis.

From the central nervous system, the organ of hearing:

- In rare cases - hearing impairment, usually reversible, and / or tinnitus, especially in patients with renal insufficiency or hypoproteinemia (nephrotic syndrome), rarely - paresthesia.

From the skin:

- rarely - skin itching, hives, other types of rash or bullous skin lesions, polymorphic erythema, exfoliative dermatitis, purpura, fever, vasculitis, eosinophilia, photosensitivity.

- extremely rare - severe anaphylactic or anaphylactoid reactions up to shock, which until now have been described only after intravenous administration.

From the peripheral blood:

- rarely - thrombocytopenia, in rare cases, leukopenia, in some cases agranulocytosis, aplastic or hemolytic anemia.

Overdose:

Symptoms: marked decrease in blood pressure, drowsiness, flaccid paralysis, apathy and confusion, collapse, shock, thrombosis, delirium, acute renal failure.

Treatment: provocation of vomiting, gastric lavage, Activated carbon, correction of indicators of water-electrolyte balance and acid-base state under the control of serum concentrations of electrolytes, hematocrit, symptomatic treatment.

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.

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 digitalic intoxication due to hypokalemia (for high- and low-polarity) and elongation of the half-life (for low-polarity).

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 administration of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists to 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 probenecid 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.

Cyclosporin A - when combined with furosemide, the risk of gouty arthritis is increased due to furosemide-induced hyperuricemia, and cyclosporine-induced excretion of urate by the kidneys.

In patients with a high risk of developing nephropathy for the introduction of radiopaque agents that received 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 intravenous hydration prior to the administration of the radiopaque.

Special instructions:

Apply strictly according to the doctor's prescription.

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 use of potassium and potassium-sparing diuretics (primarily spironolactone) is recommended, as well as a diet rich in potassium.

Increased risk of development of violations of water-electrolyte balance is observed in patients with renal insufficiency. During course treatment it is necessary to periodically monitor the concentration of plasma electrolytes (includingincluding sodium, calcium, potassium, magnesium), acid-base state, residual nitrogen, creatinine, uric acid and, if necessary, appropriate corrective therapy (with higher multiplicity in patients with frequent vomiting and parenteral fluids).

With the appearance or strengthening of azotemia and oliguria in patients with severe progressive kidney disease, it is recommended to suspend treatment.

Selection of the dosage regimen for patients with ascites against the background of cirrhosis of the liver should be performed under steady-state conditions (violations of the water-electrolyte balance may lead to the development of hepatic coma). This category of patients shows regular monitoring of plasma electrolytes.

The use of furosemide can cause a worsening of the course of systemic lupus erythematosus, an exacerbation of gout (especially in combination with other ototoxic drugs).

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

In patients in the unconscious state, with prostatic hyperplasia, narrowing of the ureters, diuretic control is necessary in connection with the possibility of acute urinary retention.

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

Form release / dosage:

Tablets of 40 mg.

Packaging:10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil. For 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store in a 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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002906/10

Date of registration:07.04.2010

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 (Furosemide )