Instructions Furosemide-Darnitsa solution for injection 1% ampoule 2 ml No. 10
Composition
active ingredient: furosemide;
1 ml of solution contains furosemide 10 mg;
Excipients: sodium chloride, sodium hydroxide, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: clear colorless or slightly yellowish liquid.
Pharmacotherapeutic group
Highly active diuretics. Sulfonamide preparations. ATC code C03C A01.
Pharmacological properties
Pharmacodynamics
Furosemide is a fast-acting loop diuretic, which results in a relatively strong and short-term diuretic effect. Furosemide blocks the Na+K+2Cl cotransporter 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 reaches the tubules in the lumen by an anion transport mechanism. The diuretic effect occurs 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 the glomerular filtration of sodium. 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 is also increased. 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 arterial hypertension.
The antihypertensive efficacy of furosemide is explained by 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 a dose of the drug.
A dose-dependent increase in diuresis and natriuresis was observed in healthy volunteers receiving furosemide in doses of 10-100 mg. The duration of action in healthy volunteers is approximately 3 hours after intravenous administration of 20 mg furosemide.
In patients, the relationship between the concentration of unbound (free) furosemide inside the tubular organs (determined on the basis of the rate of furosemide excretion into the urine) and the natriuretic effect is expressed in the form of a sigmoid curve with a minimum effective rate of furosemide excretion of approximately 10 micrograms per minute. Thus, continuous infusion of furosemide is more effective than repeated bolus injections. Moreover, beyond a certain bolus dose of the drug, no significant increase in effect is observed. The effect of furosemide is reduced if there is reduced tubular secretion or binding of the drug to albumin inside the tubules.
Pharmacokinetics
The volume of distribution of furosemide is 0.1 to 0.2 liters per 1 kg of body weight. The volume of distribution may be higher depending on the disease.
Furosemide (over 98%) forms strong compounds with blood plasma proteins, especially with albumin.
Furosemide is excreted primarily as unchanged drug by secretion into the proximal tubule. After intravenous administration, 60% to 70% of the administered dose of furosemide is excreted in this manner. The metabolite of furosemide, the glucuronide, accounts for 10-20% of the urinary excretion. The remainder of the dose is excreted in the feces, presumably by biliary secretion.
The terminal half-life of furosemide after intravenous administration is approximately 1 to 1.5 hours.
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 of the child.
Renal disease: In renal failure, the elimination of furosemide is slowed and the half-life is prolonged; the terminal half-life 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.
Congestive heart failure, severe hypertension, elderly patients. The elimination of furosemide is slowed due to reduced renal function in patients with congestive heart failure, severe hypertension and in elderly patients.
Premature and full-term infants. Depending on the level of renal maturity, furosemide elimination may be delayed. Drug metabolism is also reduced if infants have impaired glucuronidation. Terminal half-life is shorter
12 hours in a fetus from 33 weeks after fertilization of the egg. In infants from 2 months of age, the terminal clearance is similar to that in adult patients.
Indication
Edema in chronic congestive heart failure (if treatment with diuretics is necessary). Edema in acute congestive heart failure. Edema in chronic renal failure. Acute renal failure, 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). Support of forced diuresis.
Contraindication
Hypersensitivity to furosemide or to other components of the drug. Patients with an allergy to sulfonamides (for example, to sulfonamide antibiotics or sulfonylureas) may have cross-sensitivity to furosemide. Hypovolemia or dehydration. Renal failure in the form of anuria, if there is no therapeutic response to furosemide. Renal failure due to poisoning with nephrotoxic or hepatotoxic drugs. Severe hypokalemia. Severe hyponatremia. Precomatous or comatose states associated with hepatic encephalopathy.
Interaction with other medicinal products and other types of interactions
Not recommended combinations.
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 unless furosemide is administered at low doses (e.g. 40 mg in patients with normal renal function) and with a positive fluid balance when used to achieve a forced diuresis effect during cisplatin therapy.
Furosemide reduces the excretion of lithium salts and may lead to increased serum lithium levels, resulting in an increased risk of lithium toxicity, including a greater risk of cardiotoxic and neurotoxic effects of lithium. Therefore, careful monitoring of lithium levels is recommended in patients receiving this combination therapy.
Patients receiving diuretics may experience severe hypotension and deterioration of renal function, including cases of renal failure, especially when an angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin II receptor antagonist is first used, or when these drugs are first used in increased doses. It should be decided whether furosemide should be temporarily discontinued, or at least the dose of furosemide should be reduced 3 days before starting treatment, or the dose of the ACE inhibitor or angiotensin II receptor antagonist should be increased.
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 consider.
Concomitant use of non-steroidal anti-inflammatory drugs, including acetylsalicylic acid, may reduce the effect of furosemide. In dehydrated or hypovolemic patients, non-steroidal anti-inflammatory drugs 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 of phenytoin.
The use of corticosteroids, carbenoxolone, licorice root in large doses, and long-term use of laxatives may increase the risk of developing hypokalemia.
Some electrolyte imbalances (such as hypokalemia, hypomagnesemia) may increase the toxicity of certain other drugs (e.g., digitalis drugs and drugs that cause QT prolongation syndrome).
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 an increased 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. epinephrine, norepinephrine) may be reduced. The effect of curare-like muscle relaxants or theophylline may be enhanced.
The harmful effects of nephrotoxic drugs on the kidneys may be increased.
Renal impairment may develop in patients receiving concomitant therapy with furosemide 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 for contrast-induced nephropathy, a higher incidence of renal function deterioration after receiving contrast media was observed when treated with furosemide compared to high-risk patients who received only intravenous hydration before receiving contrast media.
Application features
During treatment with Furosemide-Darnitsa, constant urine outflow should be ensured. Patients with partial obstruction of urine outflow require close attention, especially in the initial stages of treatment.
Treatment with Furosemide-Darnitsa requires regular medical supervision of the patient. Particularly careful monitoring is required:
patients with arterial hypotension; patients who are at particular risk of 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. functional renal failure associated with severe liver disease; patients with hypoproteinemia, e.g. 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); renal function should be monitored and renal ultrasonography performed.
Regular monitoring of serum sodium, potassium and creatinine is generally 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 use, and diet. For example, vomiting or diarrhea can lead to a potassium deficiency.
When using the drug Furosemid-Darnitsa, it is advisable to recommend to the patient foods with a high potassium content (baked potatoes, bananas, tomatoes, spinach, dried fruits). It should be remembered that when using the drug Furosemid-Darnitsa, it may be necessary to compensate for potassium deficiency with medication.
In placebo-controlled trials of risperidone in elderly patients with dementia, higher mortality rates were observed in patients receiving furosemide concomitantly with risperidone compared with patients receiving risperidone alone 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 simultaneous use of alcohol and Furosemide-Darnitsa should be avoided.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using the drug Furosemide-Darnitsa, 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, you should refrain from driving or operating other machinery during the treatment period.
Use during pregnancy or breastfeeding
Breastfeeding. Furosemide passes into breast milk and may inhibit lactation. Women should discontinue breastfeeding during treatment with furosemide.
Method of administration and doses
The dosage regimen 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 administered intravenously only when oral administration is inappropriate or ineffective (e.g., in cases of impaired intestinal absorption) or when a rapid effect is required. In the case of intravenous therapy, it is recommended to switch to oral therapy 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 larger bolus doses administered at longer intervals.
For adults, the recommended maximum daily dose of furosemide is 1,500 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.
Special dosage recommendations
Dosage for adults is generally based on using the recommendations below.
Edema in chronic congestive heart failure. The recommended initial dose of the drug for oral administration is 20 mg to 50 mg per day. If necessary, the dose can be adjusted according to the patient's therapeutic response. It is recommended to divide the daily dose into 2 or 3 doses.
Edema in acute congestive heart failure. The recommended initial dose of the drug is 20 to 40 mg and is administered as a bolus injection. If necessary, the dose can be adjusted according to 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 predict the exact dose. In patients with chronic renal failure, the dose should be carefully titrated to ensure a gradual initial fluid loss. For adult patients, this means using a dose that results in a daily weight loss of approximately 2 kg (approximately 280 mmol Na+).
In the case of intravenous administration, the dose of furosemide can be determined as follows: treatment is initiated 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, arterial hypotension, and significant electrolyte and acid-base imbalance should be compensated for before starting furosemide.
It is recommended to switch from intravenous administration to oral administration as soon as possible.
The recommended initial dose is 40 mg 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 50 mg to 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 avoid complications such as orthostatic hypotension or disturbances of electrolyte and acid-base balance, 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 intravenous administration is absolutely necessary, the initial single dose is 20-40 mg.
Hypertensive crisis: The recommended initial dose is 20 mg to 40 mg administered as an intravenous bolus injection. The dose may be adjusted as necessary based on the patient's 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 controlled before initiating 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 mg to 40 mg and is administered intravenously.
Intravenous injection/infusion: When administered intravenously, furosemide should be administered as a slow injection or infusion at a rate not exceeding 4 mg per minute. In patients with severe hepatic impairment (serum creatinine > 5 mg/dl), an infusion rate not exceeding 2.5 mg per minute is recommended.
Intramuscular injection: The use of the drug by intramuscular injection should be limited to exceptional cases where oral and intravenous administration is inappropriate. It should be noted that the intramuscular route of administration is not indicated for the treatment of acute conditions such as pulmonary edema.
Infusion of Furosemide-Darnitsa should not be carried out together with other medications!
Furosemide-Darnitsa is a solution with a pH level of 8.8 to 9.8, which has no buffering capacity. Thus, the active ingredient may precipitate at pH values below 7. In the case of dilution of 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 quickly as possible.
Children
For children, the dose should be reduced according to body weight (see section “Method of administration and dosage”).
Overdose
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 (progressing to shock), acute renal failure, thrombosis, delirium, peripheral paralysis, apathy and confusion.
Treatment: There are no specific antidotes for furosemide. Therapy is symptomatic.
Adverse reactions
Metabolic and nutritional disorders: electrolyte imbalance (including those with clinical manifestations), dehydration and hypovolemia, especially in elderly patients, hyponatremia, hypochloremia, hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, increased triglyceride levels in the blood, increased cholesterol levels in the blood, increased creatinine levels in the blood, increased uric acid levels in the blood, gout attacks, increased urea levels in the blood, decreased glucose tolerance, the course of diabetes mellitus may transition from latent to severe, pseudo-Barter syndrome against the background of improper and/or prolonged use of furosemide.
Vascular disorders: hypotension, including orthostatic hypotension, vasculitis, thrombosis.
Renal and urinary disorders: tubulointerstitial nephritis, increased urine volume, increased urinary sodium levels, increased urinary chloride levels, urinary retention (in patients with partial urinary outflow obstruction), nephrocalcinosis/nephrolithiasis in premature infants, renal failure.
Gastrointestinal: nausea, vomiting, diarrhea, acute pancreatitis.
Hepatobiliary disorders: cholestasis, increased transaminase levels.
Hearing and balance disorders: hearing impairment, which is usually transient, especially in patients with renal insufficiency, hypoproteinemia (e.g. nephrotic syndrome) and/or in case of too rapid intravenous administration of furosemide. Cases of deafness, sometimes irreversible, have been reported after oral or intravenous administration of furosemide. Tinnitus.
Skin and subcutaneous tissue disorders: pruritus, urticaria, rash, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, photosensitivity reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP) and DRESS syndrome (drug rash with eosinophilia and systemic symptoms).
Immune system disorders: severe anaphylactic and anaphylactoid reactions (including those accompanied by shock).
Nervous system: paresthesia, hepatic encephalopathy in patients with hepatocellular insufficiency.
From the blood and lymphatic system: hemoconcentration, thrombocytopenia, leukopenia, eosinophilia, agranulocytosis, aplastic anemia or hemolytic anemia.
Congenital and hereditary/genetic disorders: Increased risk of patent ductus arteriosus if furosemide is administered to premature infants during the first days of life.
General disorders and administration site conditions: fever, local reactions, e.g. pain after intramuscular injection.
Expiration date
3 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25°C. Do not freeze.
Packaging
2 ml in an ampoule; 10 ampoules in a contour blister pack; 1 contour blister pack in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
