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

Furosemide - rapid-acting diuretic, which is a derivative of sulfonamide. Furosemide blocks the system of transport of sodium, potassium, and chlorine ions in the thick segment of the ascending knee of the Henle loop, and therefore its saluretic effect depends on the admission of the drug into the lumen of the renal tubules (due to the mechanism of anion transport). Diuretic effect of the drug Furosemide is associated with inhibition of the reabsorption of sodium chloride in this section of the Henle loop. Secondary effects on the increase in sodium excretion are: an increase in the amount of urine released (due to osmotically bound water) and an increase in the secretion of potassium in the distal part of the renal tubule.At the same time, the excretion of calcium and magnesium ions increases. With the repeated administration of the drug Furosemide its diuretic activity does not decrease, as the drug interrupts the tubular-glomerular feedback in Macula densa (tubular structure, closely related to juxtaglomerular complex). Furosemide causes dose-dependent stimulation of the renin-angiotensin-aldosterone system. With heart failure furosemide quickly 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 kidney function. The drug has an antihypertensive effect, which is caused by increased sodium excretion, a decrease in the volume of circulating blood and a decrease in the response of the smooth muscles of the vessels to vasoconstrictive effects (due to the natriuretic effect furosemide reduces the response of blood vessels to catecholamines, whose concentration in patients with hypertension is increased). Dose-dependent diuresis and natriuresis is observed when taking furosemide at a dose of 10 mg to 100 mg (healthy volunteers). After intravenous administration of 20 mg of the drug Furosemide The diuretic effect develops after 15 minutes and lasts about 3 hours.

The relationship between the intracanular concentrations of unbound (free) furosemide and its natriuretic effect is in the form of a sigmoid curve with a minimum effective furosemide excretion rate of about 10 μg / min. Therefore, prolonged infusion of furosemide is more effective than repeated bolus administration. In addition, when a certain bolus dose is exceeded, no significant increase in the effect is observed. When the tubular secretion of furosemide decreases or when the drug binds to the albumin located in the lumen of the tubules (for example, in a nephrotic syndrome), the effect of furosemide decreases.

Pharmacokinetics:

The volume of distribution of furosemide is 0.1-0.2 l / kg body weight and varies significantly depending on the underlying disease. Furosemide binds to blood plasma proteins (more than 98%), mainly with albumins. Furosemide is excreted mainly unchanged and mainly through secretion in the proximal tubules. After intravenous administration of furosemide, 60-70% of the administered dose is excreted by this route. Glucuronated furosemide metabolites are 10-20% of the kidney-excreted drug. The remaining dose is secreted through the intestine, apparently by biliary secretion. The final half-life of furosemide after intravenous administration is approximately 1-1.5 hours. Furosemide penetrates the placental barrier and is excreted in the mother's milk. Its concentration in the fetus and the newborn is the same as that of the mother.

Peculiarities of pharmacokinetics in selected groups of patients

With renal insufficiency the elimination of furosemide slows down, and the half-life increases; with severe renal failure, the final half-life can increase 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.

With hepatic insufficiency the half-life of 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.

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

In preterm and full-term children, excretion of furosemide can be slowed 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 glucuric ability is inadequate. In children, whose age after conception exceeds 33 weeks, the final half-life 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.
Edema syndrome with acute heart failure.
Edema syndrome with chronic renal failure.
Acute renal failure, including those during pregnancy and burns (to maintain fluid excretion).
Edema syndrome with nephrotic syndrome (with nephrotic syndrome in the foreground is the treatment of the underlying disease).
Edema syndrome with liver diseases (if necessary in addition to treatment with aldosterone antagonists).
Cerebral edema.
Hypertensive crisis.

Maintenance of forced diuresis in case of poisoning with chemical compounds, kidneys being excreted unchanged.

Contraindications:

Hypersensitivity to the active substance or to any of the components of the drug; in patients with an allergy to sulfonamides (sulfanilamide antimicrobial agents or urea sulfonyl preparations), a "cross" allergy may develop furosemide.
Renal failure in anuria, which does not respond to the administration of furosemide.
Hepatic precoma and coma.
Pronounced hypokalemia.
Pronounced hyponatremia.
Hypovolemia (with or without arterial hypotension) or dehydration.
RHighly expressed outflow disorders urine of any etiology (including unilateral defeat urinary tract).

Carefully:

arterial hypotension;
conditions in which excessive reduction in blood pressure is particularly dangerous (stenosing coronary and / or cerebral arteries);

acute myocardial infarction (increased risk of developing cardiogenic shock), latent or manifested diabetes mellitus;

gout;
hepatorenal syndrome (ie, with functional renal failure associated with liver disease);
increased risk of development of water-electrolyte balance and acid-alkaline state disorders or in case of significant additional fluid losses (vomiting, diarrhea, profuse sweating) (control of water-electrolyte balance and acid-base state and, if necessary, correction of these disorders prior to the use of furosemide);
hypoproteinemia (for example, with nephrotic syndrome, when it is possible to reduce the diuretic effect and increase the risk of developing the ototoxic effect of furosemide, so the dose selection in such patients should be carried out with extreme caution);
partial obstruction of the urinary tract (prostatic hyperplasia, narrowing of the urethra);
hearing loss,
pancreatitis,
ventricular arrhythmias in the anamnesis,
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), so these children need regular monitoring of kidney function and ultrasound of the kidneys is required).
while concomitant use of risperidone in elderly patients with dementia (risk of increased mortality).

Pregnancy and lactation:

Furosemide penetrates the placental barrier, so it should not be administered during pregnancy without strict indications for use. If for vital reasons Furosemide is prescribed to pregnant women, careful monitoring of the condition and development of the fetus 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:

When the drug is prescribed Furosemide it is recommended to use its lowest doses, sufficient to achieve the necessary therapeutic effect.

The drug is administered intravenously and in exceptional cases intramuscularly (when intravenous administration or oral administration is not possible). Intravenous administration of the drug Furosemide is performed only 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 if it is necessary to obtain the most rapid effect. With intravenous administration of the drug Furosemide it is always advisable to transfer the patient as soon as possible to taking Furosemide in tablets. With intravenous administration Furosemide 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 intravenous administration of the drug Furosemide did not exceed 2.5 mg per min. To achieve optimal efficiency and suppression of counterregulation (activation of the renin-angiotensin and antinatriuretic neurohumoral regulating units), a prolonged intravenous infusion of the drug should be preferred Furosemide compared with repeated intravenous bolus administration of the drug. If after one or more bolus intravenous injections in acute conditions there is no possibility of a continuous intravenous infusion, it is more preferable to administer low doses with small intervals between administrations (approximately 4 hours) than intravenous bolus administration of higher doses with longer time intervals between introductions. The solution for parenteral administration has a pH of about 9 and does not have buffer properties. At pH below 7, the active ingredient may fall into the sediment, so when the preparation is diluted Furosemide It is necessary to strive for the pH of the resulting solution to fluctuate from neutral to slightly alkaline. For dilution, 0.9% sodium chloride solution can be used. Diluted drug solution Furosemide should be used as soon as possible after cooking. The recommended maximum daily dose for intravenous administration for adults is 1500 mg. In children, the recommended dose for parenteral administration is 1 mg / kg body weight (but not more than 20 mg per day).

The duration of treatment is determined by the doctor individually, depending on the indications.

Special recommendations on the dosing regimen in adults

Edema Syndrome in Chronic Heart Failure

The recommended initial dose is 20-80 mg per day. The necessary dose is selected depending on the diuretic response. It is recommended that the daily dose be administered two to three times.

Edema in acute heart failure

The recommended initial dose is 20-40 mg as an intravenous bolus. If necessary, the dose of the drug Furosemide can be adjusted depending on the therapeutic effect.

Edema Syndrome in Chronic Renal Failure

The natriuretic reaction to furosemide depends on several factors, including the severity of renal failure and the sodium content in the blood, so the effect of the dose can not be exactly predictable. In patients with chronic renal failure, careful dose selection is required, by gradually increasing it so that fluid loss occurs gradually (at the beginning of treatment, a loss of fluid up to about 2 liters per day is possible).

In patients on hemodialysis, the usual maintenance dose is 250-1500 mg / day. When administered intravenously, the dose of Furosemide can be determined as follows: treatment begins with intravenous drip administration at a rate of 0.1 mg per minute, and then gradually increase the rate of administration every 30 minutes. depending on the therapeutic effect.

Acute renal failure (to maintain the excretion of fluid)

Before starting treatment with the drug Furosemide hypovolemia, arterial hypotension and significant disturbances in the water-electrolyte and acid-alkaline state should be eliminated. It is recommended that the patient is transferred from the intravenous route as soon as possible Furosemide on the taking of tablets Furosemide (dose of the drug Furosemide in tablets depends on the selected intravenous dose). The recommended initial intravenous dose is 40 mg. If after its introduction the necessary diuretic effect is not achieved, then Furosemide can be administered in the form of continuous intravenous infusion, starting at an administration rate of 50-100 mg per hour.

Edema with nephrotic syndrome

The recommended initial dose is 20-40 mg per day. The necessary dose is selected depending on the diuretic response.

Edema syndrome with liver diseases

Furosemide is prescribed in addition to treatment with aldosterone antagonists in case of their insufficient effectiveness. To prevent the development of complications, such as a violation of orthostatic regulation of blood circulation or disturbance of water electrolyte or acid-base state, careful dose selection is required so that the loss of fluid occurs gradually (at the beginning of treatment, a loss may occur liquid to about 0.5 kg of body weight per day). If intravenous administration is absolutely necessary, the initial dose for intravenous administration is 20-40 mg. Hypertensive crisis, cerebral edema

The recommended initial dose is 20-40 mg by intravenous bolus administration. The dose can be adjusted depending on the effect.

Maintenance of forced diuresis in poisoning

Furosemide is appointed after intravenous infusion of electrolyte solutions. The recommended initial dose for intravenous administration is 20-40 mg. The dose depends on the response to furosemide. Before and during drug treatment Furosemide it is necessary to control and restore losses of liquid and electrolytes.

Side effects:

The incidence of adverse reactions listed below was determined as follows: very often -> 10%; often -> 1%, but <10%; infrequently -> 0.1%, but less than 1%; rarely -> 0.01%, but less than 0.1%; very rarely - less than 0.01%, including individual reports; frequency is unknown (can not be calculated from available data).

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

Often: disturbances of the water-electrolyte balance, including those that occur with clinical symptoms. Symptoms that indicate the development of violations of water-electrolyte balance may be headache, convulsions, tetany, muscle weakness, heart rhythm disorders and dyspeptic disorders.These disorders can develop either gradually (for a long time) or quickly (for a very short time, for example, in the case of high doses of furosemide in patients with normal renal function). Factors contributing to the development of violations of water-electrolyte balance are the main diseases (for example, cirrhosis of the liver or heart failure); concomitant therapy with drugs that change the water-electrolyte balance; malnutrition and drinking regimen; vomiting, diarrhea, increased sweating. Dehydration and hypovolemia (decrease in the volume of circulating blood), especially in elderly patients, which can lead to hemoconcentration with a tendency to develop thrombosis (see below). Increase in the concentration of creatinine in the blood. Increase in the concentration of triglycerides in the blood serum.

Often: hyponatremia, hypochloraemia, hypokalemia, increased concentration cholesterol in the blood. Increased concentration of uric acid in the blood and exacerbation of the gout.

Infrequently: decreased glucose tolerance. A manifestation is possible

latent-flowing diabetes mellitus.

Frequency unknown: hypocalcemia, hypomagnesemia, increased concentration urea in the blood, metabolic alkalosis.

From the cardiovascular system:

Often: a marked decrease in blood pressure, including orthostatic hypotension;

Rarely: vasculitis;

Frequency unknown: thrombosis.

From the side of the kidneys and urinary system:

Often: increased urine volume;

Rarely: tubulointerstitial nephritis;

Frequency unknown: increased urinary sodium, increased urinary chloride, urinary retention (in patients with partial obstruction of the urinary tract, see section "Special instructions"), nephrocalcinosis / nephrolithiasis in premature infants (see section "Special instructions"), renal insufficiency see section "Interaction with other drugs").

From the digestive system:

Infrequently: nausea;

Rarely: vomiting, diarrhea;

Rarely: acute pancreatitis.

From the liver and bile ducts:

Rarely: cholestasis, increased activity of "liver" transaminases.

From the nervous system:

Often: hepatic encephalopathy in patients with hepatocellular insufficiency (cf.section "Contraindications"),

Rarely: paresthesia.

From the organ of hearing:

Infrequently: hearing impairment, although usually transient, especially in patients with renal insufficiency, hypoproteinemia (eg, with nephrotic syndrome) and / or too fast intravenous administration of furosemide;

Rarely: noise in ears.

From the skin:

Infrequently: pruritus, urticaria, rash, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, photosensitivity reactions;

Frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis and drug rash with eosinophilia and systemic symptoms (DRESS-syndrome).

From the immune system:

Rarely: severe anaphylactic or anaphylactoid reactions up to the development of anaphylactic shock.

On the part of the blood system:

Often: hemoconcentration;

Infrequently: thrombocytopenia;

Rarely: leukopenia, eosinophilia;

Rarely: agranulocytosis, aplastic anemia, or hemolytic anemia.

Congenital, hereditary and genetic disorders:

Frequency unknown: increased risk of non-invasion of the arterial duct, when furosemide is introduced to premature infants during the first week of life.

General violations and violations at the place of introduction:

Rarely: fever;

Frequency unknown: after intramuscular injection, a local reaction in the form of pain is possible.

Since some adverse reactions (such as a change in the blood picture, severe anaphylactic or anaphylactic reactions, severe skin allergic reactions) may, under certain conditions, threaten the life of the patient, then any side effects should immediately be reported to the doctor.

Overdose:

The clinical picture of acute or chronic drug overdose depends mainly on the extent and consequences of fluid loss and electrolytes.

Symptoms: hypovolemia, dehydration, hemoconcentration, cardiac rhythm and conduction disorders (including atrioventricular block and ventricular fibrillation). Symptoms of these disorders are lowering blood pressure (progressing up to the development of shock), acute renal failure, thrombosis, delusional state, flaccid paralysis, apathy and confusion.

Treatment is aimed at correction of clinically significant disorders of water electrolyte and acid-base state under the control of the content of electrolytes in blood serum, acid-base state, hematocrit, and prevention or therapy of possible serious complications developing against the background of these disorders.

Interaction:

Not recommended combinations

Aminoglycosides - a delay in excretion of aminoglycosides by the kidneys when they are used simultaneously with furosemide and an increased risk of ototoxic and nephrotoxic action aminoglycosides. For this reason, the use of this combination of drugs should be avoided. except when it is necessary for life indications, and in this case correction (reduction) of maintenance doses is required aminoglycosides.

Combinations where caution should be exercised

Ototoxic drugs - furosemide potentiates their ototoxicity. Since this can lead to irreversible damage to the hearing organ, these drugs should be used concomitantly with furosemide only under strict medical conditions. Cisplatinum - with simultaneous application with furosemide, there is a risk of development of ototoxic action. In addition, an increase in nephrotoxic action of cisplatin, if furosemide is not used in low doses (for example, 40 mg in patients with normal renal function) and in conjunction with appropriate hydration of the patient when it is used to perform forced diuresis during treatment with cisplatin.

Inhibitors angotensin-converting enzyme (ACE) and angiotensin II receptor antagonists (ARAN) - the administration of an ACE inhibitor and ARAP to patients previously treated with furosemide may lead to an excessive decrease in blood pressure with impaired renal function and, in some cases, to acute renal failure, therefore three days before the start of treatment with ACE inhibitors and ARAN or an increase in their dose, it is recommended that furosemide be withdrawn or reduced.

Lithium salts - under the influence of furosemide, lithium excretion decreases, which increases the serum concentration of lithium and increases the risk of developing toxic effect of lithium,including its damaging effects on the heart and nervous system. Therefore, when applying this combination, monitoring serum concentration of lithium.

Risperidone - caution should be exercised, carefully weighing the risk-benefit ratio when combined with risperidone with furosemide or other strong diuretics (there was an increase in mortality in elderly patients with dementia who received concomitantly risperidone and furosemide).

Interactions that should be taken into account

Cardiac glycosides, drugs that cause prolongation of the QT interval - in the case of development of water-electroline arrows (hypokalemia or hypomagnesemia) with furosemide, the toxic effect of cardiac glycosides and drugs causing prolongation of the QT interval increases (the risk of rhythm disturbances increases ).

Glucocorticosteroids, licorice preparations, in large quantities and prolonged use of laxatives combined with furosemide increase the risk of hypokalemia.

Medicines with nephrotoxic action - when combined with furosemide, the risk of developing their nephrotoxic effect increases. High doses Some cephalosporins (especially those with a predominantly renal excretory route) - in combination with furosemide, the risk of nephrotoxic action increases. Non-steroidal Anti-inflammatory drugs (NSAIDs) - NSAIDs, including acetylsalicylic acid, can reduce the diuretic effect of furosemide. In patients with hypovolemia and dehydration (including those taking furosemide), NSAIDs can cause the development of acute renal failure. Furosemide can increase the toxicity of salicylates.

Phenytoin - decrease diuretic actions furosemide.

Hypotensive drugs, diuretics or other drugs, to reduce blood pressure - when combined with furosemide, a more pronounced decrease in blood pressure is expected.

Probenecid, 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. All this increases the risk of side effects of furosemide, as well as taken simultaneously the above drugs. Hypoglycemic agents, pressor amines (epinephrine, norepinephrine) - weakening effects when combined with furosemide.

Theophylline, diazoxide, curare like muscle relaxants - enhancing effects when combined with furosemide.

Sucralfate - decrease in absorption of furosemide when it is ingested (not provided for this dosage form) and weakening its effect (furosemide and sucralfate should be taken at intervals of not less than two hours). 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. Radiopaque means - in patients with a high risk of developing nephropathy on the administration of radiocontrast preparations that received furosemide, a higher incidence of renal dysfunction was observed compared to patients at high risk of developing nephropathy for the introduction of radiopaque preparations that received only intravenous hydration prior to the administration of the radiopaque preparation.

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

Special instructions:

Before starting treatment with the drug Furosemide It is necessary to exclude the presence of sharply expressed violations of the outflow of urine, including unilateral ones.

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

During treatment with the drug Furosemide typically requires regular monitoring of sodium, potassium, and creatinine, especially careful control should be performed in patients with high risk of disturbances of water and electrolyte balance in the cases of additional fluid and electrolyte losses (e.g., due to vomiting, diarrhea or intense sweating). Before and during drug treatment Furosemide must be checked and, in case of, eliminate hypovolemia or dehydration, as well as clinically significant disorders vodnoelektrolitnogo and / or acid-base status, which may require short-term cessation of drug treatment Furosemide. When treating the drug Furosemide it is always advisable to consume foods rich in potassium (lean meat, potatoes, bananas, tomatoes, cauliflower, spinach, dried fruits, etc.).In some cases, the intake of potassium preparations or the administration of potassium-sparing drugs may be indicated.

In premature infants - regular monitoring of kidney function and ultrasound examination of the kidneys (the possibility of nephrolithiasis and nephrocalcinosis) is required. There was a high incidence of fatalities in elderly patients who simultaneously received risperidone and furosemide, compared with those patients who received one risperidone or one furosemide.

The mechanism of this effect is unclear. The simultaneous use of risperidone with other diuretics (mainly low doses of thiazide diuretics) was not associated with an increase in mortality in elderly patients with dementia. In elderly patients with dementia, caution should be exercised, carefully weighing the benefit / risk ratio, appointing furosemide and risperidone Simultaneously. Since dehydration is a common risk factor for increasing mortality, when deciding to use this combination in elderly patients with dementia, patients should be dehydrated.

The choice of dosage regimen for patients with ascites against the background of liver cirrhosis should be performed in a hospital (violations of the water-electrolyte state can lead to the development of hepatic coma).

Compatibility Guidelines

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

Emergency measures in the development of anaphylactic shock

As a rule, the following measures are recommended: at the first signs (severe weakness, cold sweat, nausea, cyanosis) stop the injection, leaving the needle in the vein. Along with other usual urgent measures, it is necessary to ensure a low position of the head and trunk and maintain airway patency. Urgent medication (recommendations for dosage are calculated for an adult with normal body weight, when treating children, the dosage should be reduced in proportion to the body weight):

Immediate intravenous injection of epinephrine (adrenaline): after diluting 1 ml of a standard epinephrine (adrenaline) solution 1: 1000 to 10 ml, 1 ml of the resulting solution (0.1 mg of epinephrine) is slowly introduced at the beginning, under the control of the heart rate,blood pressure and heart rate). If necessary, the introduction of epinephrine (adrenaline) can be continued by intravenous infusion. Simultaneously with the introduction of epinephrine (adrenaline), intravenous glucocorticosteroids (250-1000 mg of methylprednisolone or prednisolone) are produced, which can be repeated if necessary. In addition to these measures, intravenous infusion of plasma substitutes and / or electrolyte solutions is used to replenish the volume of circulating blood.

If necessary: artificial respiration, inhalation of oxygen, antihistamines.

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

Some side effects (for example, a significant reduction in blood pressure) may impair the ability to concentrate and the speed of the psychomotor reaction, which can be dangerous when driving or engaging in other potentially hazardous activities. Especially it refers to the period of starting treatment or increasing the dose of the drug, as well as to the cases of simultaneous use of antihypertensive drugs or alcohol.

In such cases, it is not recommended to drive vehicles or engage in potentially hazardous activities.

Form release / dosage:Solution for intravenous and intramuscular injection 10 mg / ml.

Packaging:2 ml each into ampoules of colorless neutral glass type I according to ISO 9187 with a colored break ring or with a colored dot and a notch or without a kink ring, a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding can additionally be applied to the ampoules. 5 ampoules per circuit cell packaging of films

polyvinylchloride and aluminum foil lacquer or film polymeric, or without foil and without film. Or 5 ampoules are placed in a prefabricated form (tray) made of cardboard for consumer containers with cells for packing ampoules.

One or two contour squares or cardboard trays, together with an instruction for use and a scarifier or knife, ampoule, or without a scarifier and a knife ampoule, are placed in a cardboard package (bundle).

Storage conditions:

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

Do not freeze.

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:LP-002243

Date of registration:23.09.2013

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp12.11.2015

Illustrated instructions

Instructions

Furosemide (Furosemide)