Furosemide Darnytsia tablets 40 mg 50 pcs.

Pharmacodynamics. Furosemide is a fast-acting loop diuretic that causes a relatively strong and short-term diuretic effect. Furosemide blocks the Na + K + 2Cl cotransporter, which is located in the basal membranes of the cells of the thick segment of the ascending limb of the loop of Henle: the effectiveness of the saluretic action of furosemide therefore depends on whether the drug enters the tubules at the lumen sites by the anion transport mechanism. The diuretic effect develops as a result of inhibition of sodium chloride reabsorption in this segment of the loop of Henle. As a result, the fractional excretion of sodium can reach 35% of glomerular sodium filtration. Secondary effects of increased sodium excretion are increased urine output (due to osmotically bound water) and increased distal tubular secretion of potassium. The excretion of calcium and magnesium ions also increases. Furosemide causes dose-dependent stimulation of the renin-angiotensin-aldosterone system. In heart failure, furosemide leads to an acute reduction in cardiac preload (by constricting the capacious venous vessels). This early vascular effect is prostaglandin-mediated and assumes adequate renal function with activation of the renin-angiotensin system and intact prostaglandin synthesis. In addition, due to its inherent natriuretic effect, furosemide reduces vascular reactivity to catecholamines, which is increased in patients with atrial fibrillation.

The antihypertensive efficacy of furosemide is due to increased sodium excretion, decreased blood volume, and reduced vascular smooth muscle response to stimulation by vasoconstrictors or vasoconstrictor agents.

The onset of the diuretic effect is observed within 15 minutes after intravenous administration of the drug dose.

A dose-dependent increase in diuresis and natriuresis was noted in healthy volunteers receiving furosemide at a dose of 10-100 mg. The duration of action in healthy volunteers is about 3 hours after intravenous administration of 20 mg of furosemide.

In patients, the relationship between the concentrations of unbound (free) furosemide inside the tubular organs (determined on the basis of the rate of furosemide excretion in the urine) and the natriuretic effect is expressed in the form of a sigmoid curve with a minimum effective rate of furosemide excretion of about 10 μg/min. Thus, continuous i.v. infusion of furosemide is more effective than repeated bolus injections. Moreover, beyond a certain bolus dose of the drug, there is no significant increase in the severity of the effect. The effect of furosemide is reduced if there is reduced tubular secretion or binding of the drug to albumin inside the tubules.

Pharmacokinetics. Furosemide is rapidly absorbed from the gastrointestinal tract. The maximum absorption time is 1-1.5 hours. The absorption of the drug shows significant individual variability.

The bioavailability of furosemide in healthy volunteers is about 50-70% for tablets. In patients, the bioavailability of the drug is affected by various factors, including existing diseases. For example, in nephrotic syndrome, bioavailability may decrease to 30%.

Taking food at the same time as furosemide may affect the absorption of furosemide.

The volume of distribution of furosemide is 0.1-0.2 l/kg body weight. The volume of distribution may be higher depending on the disease.

Furosemide (more than 98%) forms strong compounds with blood plasma proteins, especially with albumin.

Furosemide is excreted mainly as unchanged drug by secretion into the proximal tubule.

The metabolite of furosemide, the glucuronide, accounts for 10-20% of the substance in the urine. The remaining dose is excreted in the feces, probably by biliary secretion.

Furosemide penetrates into breast milk, crosses the placental barrier and slowly reaches the fetus. Furosemide is detected in the fetus or newborn in the same concentrations as in the mother.

Renal disease. In renal failure, furosemide elimination is slowed and T½ _is prolonged; the final T½ _may be up to 24 hours in patients with severe renal failure.

In nephrotic syndrome, reduced plasma protein concentrations lead to increased concentrations of unbound (free) furosemide. On the other hand, the efficacy of furosemide in these patients is reduced due to binding to intratubular albumin and reduced tubular secretion.

Furosemide is poorly dialyzable in patients undergoing hemodialysis, peritoneal dialysis, and chronic outpatient peritoneal dialysis.

Hepatic insufficiency. In hepatic insufficiency, the T½ _of furosemide increases by 30-90%, mainly due to a larger volume of distribution. A wide variety of all pharmacokinetic parameters is observed in this group of patients.

Congestive heart failure, severe hypertension, elderly patients. Due to reduced renal function in such patients, the elimination of furosemide is slowed.

Premature and full-term infants. Depending on the level of renal development, furosemide excretion may be delayed. Drug metabolism is also reduced if infants have impaired glucuronidation. The terminal T½ _is less than 12 hours in fetuses older than 33 weeks after fertilization. In infants older than 2 months, the terminal clearance is the same as in adult patients.

Edema in chronic congestive heart failure (if treatment with diuretics is necessary).

Edema in acute congestive heart failure.

Edema in chronic renal failure.

Acute respiratory distress syndrome, including in pregnant women or during childbirth.

Edema in liver diseases (if necessary, to supplement treatment with aldosterone antagonists).

Hypertensive crisis (as a supportive measure).

Solution for injection – support of forced diuresis.

Tablets. The dosage regimen is set by the doctor individually depending on the severity of water-electrolyte balance disorders, the value of glomerular filtration, and the severity of the patient’s condition. The drug is usually used on an empty stomach.

For adults, the maximum total daily dose of Furosemide Darnytsia should not exceed 1500 mg.

Special dosage recommendations for adults

In edema in chronic congestive heart failure, the initial oral dose is 40 mg/day. If necessary, the dose can be adjusted depending on the patient’s therapeutic response. It is recommended to take the daily dose divided into 2 or 3 doses.

In edema in chronic renal failure, the dose should be carefully titrated to ensure a gradual initial fluid loss. For adult patients, this means administering a dose that results in a daily weight loss of approximately 2 kg (approximately 280 mmol Na ^+). The recommended initial daily oral dose is 40-80 mg. If necessary, the dose can be adjusted depending on the patient’s therapeutic response. The total daily dose can be administered as a single dose or divided into 2 doses. For patients on hemodialysis, the total daily oral dose is 250-1500 mg.

In acute renal failure, hypovolemia, hypotension, and significant electrolyte and acid-base imbalances should be corrected before starting furosemide. The transition from intravenous to oral administration should be made as soon as possible.

For edema in nephrotic syndrome, the initial oral dose is 40-80 mg/day. If necessary, the dose can be adjusted depending on the patient’s therapeutic response. The total daily dose can be administered as a single dose or divided into several doses.

In edema in liver diseases Furosemide Darnytsia is prescribed as an adjunct to aldosterone antagonist therapy in cases where the use of aldosterone antagonists alone is insufficient. To prevent complications such as orthostatic hypotension or electrolyte and acid-base imbalance, the dose should be carefully titrated to ensure a gradual initial loss of fluid. For adult patients, this means prescribing a dose that results in a daily weight loss of approximately 0.5 kg. The recommended initial daily oral dose is 40-80 mg. If necessary, the dose can be adjusted depending on the patient’s therapeutic response. The daily dose can be administered once or divided into several doses.

The drug in this dosage form is prescribed to children weighing 10 kg. For children, the recommended dose of furosemide for oral administration is 2 mg/kg body weight, but the maximum daily dose should not exceed 40 mg.

Solution for injection. The regimen of use is set by the doctor individually depending on the severity of water and electrolyte balance disorders, the value of glomerular filtration, the severity of the patient’s condition. During the use of the drug, the indicators of water and electrolyte balance should be adjusted taking into account diuresis and the dynamics of the patient’s general condition.

Furosemide is prescribed intravenously only when oral administration is inappropriate or ineffective (for example, when absorption in the intestine is impaired) or when a rapid effect is required. When using intravenous therapy, it is recommended to switch to oral administration as soon as possible.

To achieve optimal efficacy and to suppress counterregulation, continuous infusion of furosemide is generally preferred over repeated bolus injections.

In cases where continuous infusion of furosemide is not appropriate for further treatment after administration of one or more bolus doses, a further treatment regimen with low doses administered at short intervals (approximately 4 hours) is preferred over high bolus doses administered at long intervals.

For adults, the recommended maximum daily dose of furosemide is 1500 mg.

For children, the recommended dose of furosemide for parenteral administration is 1 mg/kg body weight, but the maximum daily dose should not exceed 20 mg.

Specific dosage recommendations: Dosage for adults is generally based on the use of the following recommendations.

Edema in chronic congestive heart failure. The recommended initial dose of the drug is 20-50 mg/day. If necessary, the dose can be adjusted according to the patient’s therapeutic response. It is recommended to take the daily dose divided into 2 or 3 doses.

Edema in acute congestive heart failure. The recommended initial dose of the drug is 20-40 mg/day and is administered as a bolus injection. If necessary, the dose can be adjusted based on the patient’s therapeutic response.

Edema in chronic renal failure. The natriuretic effect of furosemide depends on a number of factors, including the severity of renal failure and sodium balance. Therefore, it is not possible to accurately predict the effectiveness of the dose. In patients with chronic renal failure, the dose should be carefully titrated to ensure a gradual initial loss of fluid. For adult patients, this means using a dose that results in a daily weight loss of approximately 2 kg (about 280 mmol Na ^+).

In the case of intravenous administration, the dose of furosemide can be determined as follows: treatment begins with a continuous intravenous infusion of 0.1 mg over 1 minute, then the infusion rate is increased every half hour depending on the patient’s response.

In acute renal failure, hypovolemia, hypotension, and significant electrolyte and acid-base imbalance should be corrected before starting furosemide.

You should switch from IV administration to oral administration as soon as possible.

The recommended initial dose is 40 mg and is administered as an intravenous injection. If this dose does not result in the desired increase in fluid excretion, furosemide can be administered as a continuous intravenous infusion, starting with the administration of 50-100 mg of the drug over 1 hour.

Edema in liver disease. Furosemide is prescribed as an adjunct to aldosterone antagonist therapy in cases where the use of aldosterone antagonists alone is insufficient. To prevent complications such as orthostatic hypotension or electrolyte and acid-base imbalance, the dose should be carefully titrated to ensure a gradual initial loss of fluid. For adult patients, this means administering a dose that results in a daily weight loss of approximately 0.5 kg. If IV administration is absolutely necessary, the initial single dose is 20-40 mg.

Hypertensive crisis. The recommended initial dose is 20-40 mg administered as an intravenous bolus injection. If necessary, the dose can be adjusted depending on the patient’s therapeutic response.

Support of forced diuresis in case of poisoning. Furosemide is administered intravenously in addition to the administration of infusions of electrolyte solutions. The dose depends on the therapeutic response to furosemide. Fluid and electrolyte losses should be corrected during the initiation period and during treatment. In case of poisoning with acidic or alkaline substances, fluid excretion can be accelerated by alkalinization or oxidation of the urine, respectively.

The recommended initial dose is 20-40 mg and is administered intravenously.

Special recommendations for use

IV injection/infusion: In the case of IV administration, furosemide should be administered as a slow injection or infusion at a rate of no more than 4 mg per minute. In patients with severe liver dysfunction (plasma creatinine 5 mg/dl), an infusion rate of no more than 2.5 mg per minute is recommended.

Intramuscular injection: The use of the drug as an intramuscular injection should be limited to exceptional cases where oral and intravenous administration are inappropriate. It should be noted that the intramuscular injection route is not indicated for the treatment of acute conditions such as pulmonary edema.

Infusion of the drug Furosemide Darnytsia should not be carried out together with other drugs!

Furosemide Darnytsia is a solution with a pH level of 8.8-9.8, which has no buffer capacity. Thus, the active ingredient may precipitate at pH values ​​of 7. When diluting this solution, care should be taken to ensure that the pH of the diluted solution is in the range from slightly alkaline to neutral.

0.9% sodium chloride solution can be used as a diluent. It is recommended to use diluted solutions as soon as possible.

Hypersensitivity to furosemide or other components of the drug. Patients with an allergy to sulfonamides (e.g. sulfonamide antibiotics or sulfonylureas) may show cross-sensitivity to furosemide.

Hypovolemia or dehydration.

Renal failure in the form of anuria, if no therapeutic response to furosemide is detected.

Renal failure due to poisoning with nephrotoxic or hepatotoxic drugs.

Severe hypokalemia.

Severe hyponatremia.

Precomatose or comatose states associated with hepatic encephalopathy.

From the side of the organs of hearing and vestibular apparatus: hearing impairment, usually reversible, especially in patients with renal failure, hypoproteinemia (for example, in nephrotic syndrome) and / or in the case of too rapid intravenous administration of furosemide. Cases of deafness, sometimes irreversible, have been reported after oral administration or injection of furosemide. tinnitus.

On the part of the digestive system: nausea, vomiting, diarrhea, acute pancreatitis.

Liver and biliary tract: cholestasis, increased transaminase levels.

On the part of the kidneys and urinary system: tubulointerstitial nephritis, increased urine volume, increased sodium levels in the urine, increased chlorine levels in the urine, urinary retention (in patients with partial obstruction of urine outflow), nephrocalcinosis / nephrolithiasis in premature infants, renal failure.

From the side of metabolism: electrolyte imbalance (including with clinical manifestations), dehydration and hypovolemia, especially in elderly patients, hyponatremia, hypochloremia, hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, increased levels of TG, cholesterol, creatinine, uric acid in the blood, gout attacks, increased levels of urea in the blood, decreased glucose tolerance, the course of diabetes mellitus may transition from a latent form to a pronounced one, pseudo-Barter syndrome against the background of improper and / or prolonged use of furosemide.

Nervous system: paresthesia, hepatic encephalopathy in patients with hepatocellular insufficiency.

From the cardiovascular system: hypotension, including orthostatic, vasculitis, thrombosis.

From the blood and lymphatic system: hemoconcentration, thrombocytopenia, leukopenia, eosinophilia, agranulocytosis, aplastic or hemolytic anemia.

Immune system disorders: severe anaphylactic and anaphylactoid reactions (including those accompanied by shock).

Skin and subcutaneous tissue disorders: pruritus, urticaria, rash, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, photosensitivity reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis and DRESS syndrome (drug rash with eosinophilia and systemic symptoms).

General disorders and administration site conditions: fever, local reactions, e.g. pain after injection.

Congenital and hereditary/genetic disorders: Increased risk of ductus arteriosus obstruction if furosemide is administered to premature infants during the first days of life.

During treatment with furosemide, it is necessary to ensure a constant outflow of urine. Patients with partial obstruction of urine outflow require close attention, especially in the initial stages of treatment.

Treatment with furosemide requires regular medical supervision. Particularly careful monitoring is required:

– patients with arterial hypotension;

– patients who are at particular risk due to a significant decrease in blood pressure, for example patients with severe stenosis of the coronary arteries or blood vessels supplying the brain;

– patients with latent or severe diabetes mellitus;

– patients with gout;

– patients with hepatorenal syndrome, i.e. with functional renal failure associated with severe liver disease;

– patients with hypoproteinemia associated with nephrotic syndrome (the effect of furosemide may be weakened simultaneously with potentiation of ototoxicity). Careful dose titration is necessary;

– premature infants (possible development of nephrocalcinosis/nephrolithiasis); monitoring of renal function and renal ultrasonography are required.

Regular monitoring of plasma sodium, potassium and creatinine is recommended during furosemide therapy. Particularly careful monitoring is required in patients at high risk of developing electrolyte imbalances or in cases of significant additional fluid loss (e.g. as a result of vomiting, diarrhoea or excessive sweating). Hypovolaemia or dehydration, as well as any significant disturbances of electrolyte and acid-base balance, should be corrected. This may require temporary discontinuation of furosemide therapy.

The development of electrolyte imbalances is influenced by factors such as existing diseases (e.g. cirrhosis, heart failure), concomitant medication, and diet. For example, vomiting or diarrhea can lead to potassium deficiency.

When using furosemide, it is advisable to recommend that the patient consume foods with a high potassium content (baked potatoes, bananas, tomatoes, spinach, dried fruits). It should be remembered that when using furosemide, there may be a need for drug compensation of potassium deficiency.

Concomitant use with risperidone: In placebo-controlled trials of risperidone in elderly patients with dementia, higher mortality rates were observed in patients receiving furosemide and risperidone concomitantly compared with patients receiving risperidone or furosemide alone.

Caution should be exercised and the risks and benefits carefully weighed before deciding to use this combination or concomitant treatment with other potent diuretics. Dehydration should be avoided.

The drug contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Use during pregnancy and breastfeeding. Pregnancy. Furosemide crosses the placental barrier. It should not be prescribed during pregnancy.

Breastfeeding. Furosemide passes into breast milk and may inhibit lactation. Women should discontinue breastfeeding during treatment with furosemide.

Children: For children, the dose should be reduced according to body weight (see Method of administration).

For children who cannot take the oral dosage form, such as premature infants and neonates, parenteral administration should be considered.

Ability to influence the reaction speed when driving vehicles or other mechanisms. Some side effects (for example, an unexpected significant decrease in blood pressure) may impair the patient’s ability to concentrate and the speed of his reaction, therefore, during the period of treatment, one should refrain from driving vehicles or working with mechanisms.

Combinations that are not recommended. In some cases, taking furosemide within 24 hours of chloral hydrate may cause flushing, increased sweating, agitation, nausea, increased blood pressure, and tachycardia. Therefore, the simultaneous use of furosemide and chloral hydrate is not recommended.

Furosemide may potentiate the ototoxicity of aminoglycosides and other ototoxic drugs. As this may result in irreversible damage, these drugs should not be used concomitantly with furosemide.

Combinations requiring precautions. There is a risk of ototoxic effects when cisplatin and furosemide are used concomitantly. In addition, the nephrotoxicity of cisplatin may be enhanced if furosemide is not administered at low doses (e.g. 40 mg in patients with normal renal function) and with a positive fluid balance when the drug is used to achieve a forced diuresis effect during cisplatin therapy.

Furosemide reduces the excretion of lithium salts and may lead to increased plasma lithium levels, resulting in an increased risk of lithium toxicity, including a higher risk of cardiotoxic and neurotoxic effects of lithium. Therefore, careful monitoring of lithium levels is recommended in patients receiving this combination therapy.

In patients receiving diuretics, severe hypotension and deterioration of renal function, including cases of renal failure, may occur, especially when an ACE inhibitor or an angiotensin II receptor antagonist is first used, or when these drugs are first used in high doses. It should be decided whether to temporarily discontinue furosemide, or at least reduce the dose of furosemide 3 days before starting treatment, and increase the dose of the ACE inhibitor or angiotensin II receptor antagonist.

Risperidone: Caution should be exercised and the risk and benefit should be carefully weighed before deciding on combination therapy or concomitant use with furosemide or other potent diuretics.

Combinations to be used with caution. Concomitant use of NSAIDs, including acetylsalicylic acid, may reduce the effect of furosemide. In patients with dehydration or hypovolemia, NSAIDs may lead to acute heart failure. Salicylate toxicity may be increased by furosemide.

A decrease in the effectiveness of furosemide may occur after concomitant use with phenytoin.

The use of corticosteroids, carbenoxolone, licorice root in large doses, and prolonged use of laxatives may increase the risk of developing hypokalemia.

Some electrolyte imbalances (such as hypokalemia, hypomagnesemia) may increase the toxicity of some other drugs (e.g. digitalis drugs and drugs that cause QT prolongation syndrome).

If antihypertensive drugs, diuretics or other drugs with blood pressure-lowering properties are used simultaneously with furosemide, an even greater decrease in blood pressure should be expected.

Probenecid, methotrexate and other drugs, such as furosemide, which are subject to significant renal tubular secretion, may reduce the effectiveness of furosemide. Conversely, furosemide may reduce the renal excretion of these drugs. Treatment with high doses (including both furosemide and other drugs) may lead to increased serum levels and the risk of side effects caused by furosemide or concomitant therapy.

The effectiveness of antidiabetic drugs and sympathomimetics that have the property of increasing blood pressure (e.g. adrenaline, noradrenaline) may be reduced. The effect of curare or theophylline may be enhanced.

The harmful effects of nephrotoxic drugs on the kidneys may be increased.

Renal impairment may develop in patients receiving furosemide therapy and high doses of certain cephalosporins.

Concomitant use of cyclosporine A and furosemide is associated with an increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine-induced impaired renal urate excretion.

In patients at high risk of nephropathy resulting from radiocontrast therapy, a higher incidence of renal function deterioration after receiving radiocontrast was observed in patients treated with furosemide compared with high-risk patients who received only intravenous hydration before administration of radiocontrast.

Symptoms: The clinical picture of acute or chronic overdose depends mainly on the degree and consequences of electrolyte and fluid loss and includes signs such as hypovolemia, dehydration, hemoconcentration, cardiac arrhythmias (including AV block and ventricular fibrillation). Symptoms of these disorders include severe arterial hypotension (progressive to shock), acute renal failure, thrombosis, delirium, peripheral paralysis, apathy and confusion.

Treatment: There are no specific antidotes for furosemide. Therapy is symptomatic.

In the original packaging at a temperature not exceeding 25 °C. Do not freeze the solution for injection.