Instructions for Furosemide-Darnitsa tablets 40 mg No. 50
Composition
active ingredient: furosemide;
1 tablet contains furosemide 40 mg;
Excipients: potato starch, lactose monohydrate, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: flat-cylindrical tablets of white or white with a creamy tint.
Pharmacotherapeutic group
Highly active diuretics. Simple sulfonamide preparations. Furosemide. ATX code C03C A01.
Pharmacological properties
Pharmacodynamics
Furosemide is a fast-acting loop diuretic with 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 the drug reaching the tubules at the lumen sites by an anion transport mechanism. The diuretic effect results from the reabsorption of sodium chloride 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 a dose-dependent stimulation of the renin-angiotensin-aldosterone system. In heart failure, furosemide leads to an acute reduction in cardiac overload (by constricting the capacious venous vessels). This early vascular effect is prostaglandin-mediated and occurs in the presence of adequate renal function with activation of the renin-angiotensin system and intact prostaglandin synthesis. In addition, due to its inherent natriuretic effect, furosemide reduces the increased vascular reactivity to catecholamines in patients with arterial hypertension.
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 1 hour after oral administration of the drug.
A dose-dependent increase in diuresis and natriuresis was observed in healthy subjects receiving furosemide in doses of 10-100 mg. The duration of action in healthy subjects is approximately 3-6 hours after oral administration of 40 mg furosemide.
The effect of furosemide is reduced if there is reduced tubular secretion or interaction of the drug with albumin inside the tubules.
Pharmacokinetics
Furosemide is rapidly absorbed from the gastrointestinal tract. The maximum absorption time is from 1 to 1.5 hours. The absorption of the drug shows significant individual variability.
The bioavailability of furosemide in healthy volunteers is approximately 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 be reduced to 30%.
Taking food at the same time as taking furosemide may affect the absorption of furosemide.
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 (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 is excreted in breast milk; it 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.
Kidney 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.
Liver failure.
In hepatic insufficiency, the half-life 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.
Depending on the level of renal development, the elimination of furosemide may be delayed. The metabolism of the drug is also reduced if the ability to glucuronidate is impaired in infants. The terminal half-life 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.
Indication
Edema in chronic congestive heart failure (if treatment with diuretics is necessary). Edema in nephrotic syndrome (if treatment with diuretics is necessary). 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). Arterial hypertension.
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 in the absence of a therapeutic response to furosemide. Renal failure due to poisoning with nephrotoxic or hepatotoxic drugs. Severe hypokalemia. Severe hyponatremia. Precomatous and comatose states associated with hepatic encephalopathy. Breastfeeding. Pregnancy.
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 combination of furosemide and chloral hydrate is not recommended.
Furosemide may potentiate the ototoxicity of aminoglycosides and other ototoxic drugs. As this may lead to 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 positive fluid balance when used to achieve a forced diuresis effect during cisplatin therapy.
Oral furosemide and sucralfate should not be administered less than 2 hours apart, as sucralfate reduces the absorption of furosemide from the intestine, i.e. reduces its effect.
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. 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 risks and benefits carefully weighed before deciding on combination therapy or concomitant use with furosemide or other potent diuretics.
Combinations to consider.
Concomitant use of NSAIDs, including acetylsalicylic acid, may reduce the effect of furosemide. In dehydrated or hypovolemic patients, 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 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 that, like furosemide, undergo significant tubular secretion in the kidneys 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.
It is possible to increase the harmful effects of nephrotoxic drugs on the kidneys.
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 impairment of renal urate excretion.
In patients at high risk for radiocontrast-induced nephropathy, a higher incidence of renal function deterioration after radiocontrast was observed when treated with furosemide compared with high-risk patients who received only intravenous hydration before radiocontrast.
Application features
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 blood to 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 required; premature infants (possible development of nephrocalcinosis/nephrolithiasis); monitoring of renal function and renal ultrasonography are required.
Regular monitoring of serum 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 a 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 plus risperidone compared to 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 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.
Ability to influence 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 react quickly, so during the treatment period, you should refrain from driving or operating machinery.
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, and the severity of the patient's condition. The drug is usually administered on an empty stomach.
For adults, the maximum total daily dose of Furosemide-Darnitsa should not exceed 1500 mg.
Specific dosage recommendations for adults.
For edema in chronic congestive heart failure, the recommended initial dose of the drug for oral administration is 40 mg per 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 the case of 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. It is recommended to switch from intravenous to oral administration as soon as possible.
For edema in nephrotic syndrome, the recommended initial oral dose is 40-80 mg per 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 in divided doses.
In edema in liver diseases Furosemide-Darnitsa 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 total daily dose can be administered as a single dose or divided into several doses.
The drug in this dosage form should be prescribed to children weighing more than 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.
Children
For children, the dose should be reduced according to body weight (see section “Method of administration and dosage”).
For children who cannot take the oral dosage form, such as premature infants and neonates, parenteral administration should be considered.
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 to 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 creatinine in the blood, increased uric acid in the blood, gout attacks, increased urea in the blood, pseudo-Bartter syndrome against the background of improper and/or prolonged use of furosemide, increased triglycerides in the blood, increased cholesterol in the blood, decreased glucose tolerance. The course of diabetes mellitus may transition from latent to severe.
Vascular: hypotension, including orthostatic hypotension (when used as intravenous infusion), vasculitis, thrombosis.
Renal and urinary tract disorders: increased urine volume, increased urinary sodium levels, increased urinary chloride levels, urinary retention (in patients with partial urinary outflow obstruction), tubulointerstitial nephritis, nephrocalcinosis/nephrolithiasis in premature infants, renal failure.
Gastrointestinal: nausea, vomiting, diarrhea, acute pancreatitis.
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 administration of furosemide. Cases of deafness, sometimes irreversible, have been reported after oral 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 or 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 weeks of life.
General disorders: increased body temperature.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a contour blister pack; 5 contour blister packs in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its place of business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
