Instructions Furosemide tablets 40 mg blister No. 50
Composition
active ingredient: furosemide;
1 tablet contains furosemide in terms of 100% dry matter - 40 mg;
Excipients: corn starch, microcrystalline cellulose, magnesium stearate, povidone, polyethylene glycol (macrogols), lactose monohydrate.
Dosage form
Pills.
Main physicochemical properties: round tablets, white with a yellowish tinge, with a biconvex surface.
Pharmacotherapeutic group
Highly active diuretics. ATC code C03C A01.
Pharmacological properties
Pharmacodynamics.
Furosemide is a loop diuretic that inhibits the absorption of sodium and chloride ions in the ascending limb of the loop of Henle, the proximal and distal tubules of the nephron. The effect in the distal tubules is independent of the inhibitory effect of carbonic anhydrase or the effect of aldosterone. The pharmacological action of furosemide is limited to the kidneys.
Pharmacokinetics.
The onset of diuretic action occurs approximately 1 hour after oral administration. The duration of diuretic action is 3-6 hours.
When administered orally, the drug is rapidly absorbed from the gastrointestinal tract, with an average bioavailability of 50-70%.
Distribution. Characterized by a high degree of binding to plasma proteins, mainly albumin. In healthy subjects, plasma concentrations vary from 1 to 400 μg/ml, with 91-99% of furosemide bound to plasma proteins. Furosemide crosses the placental barrier and slowly reaches the fetus.
Metabolism: Glucuronides of furosemide are one or at least the major metabolites of its biotransformation in humans. A small amount is metabolized by side chain cleavage.
Excretion: Urinary excretion (glomerular filtration and proximal tubular secretion) accounts for about 66% of the dose, with the remainder excreted in the feces. A significantly larger amount of furosemide is excreted after intravenous administration than after oral administration (tablets or solution). Furosemide is excreted in breast milk.
Half-life: Furosemide has a biphasic half-life of approximately 2 hours. The half-life is prolonged in patients with renal or hepatic insufficiency.
Indication
Edema in chronic congestive heart failure (if treatment with diuretics is necessary).
Edema in chronic renal failure.
Acute renal failure, including in pregnant women or during childbirth.
Edema in nephrotic syndrome (if treatment with diuretics is necessary).
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.
Hypersensitivity to sulfonamides (e.g., sulfonamide antibiotics or sulfonylureas) due to possible cross-sensitivity to furosemide.
Hypovolemia or dehydration.
Anuria or renal failure with anuria, in which there is no therapeutic response to furosemide.
Renal failure due to poisoning with nephrotoxic or hepatotoxic drugs or renal failure associated with hepatic coma.
Severe hypokalemia.
Severe hyponatremia.
Precomatose and comatose states associated with hepatic encephalopathy.
Interaction with other medicinal products and other types of interactions
Not recommended combinations.
Chloral hydrate: In rare cases, taking furosemide within 24 hours of chloral hydrate administration may cause flushing, increased sweating, agitation, nausea, increased blood pressure, and tachycardia. Concomitant use of furosemide and chloral hydrate is not recommended.
Drugs with increased risk of ototoxicity: aminoglycosides (e.g. kanamycin, gentamicin, tobramycin), vancomycin, teicoplanin. Furosemide may potentiate the ototoxicity of the latter. As this may lead to irreversible hearing loss, these drugs should not be used concomitantly with furosemide.
Combinations requiring precautions.
Cisplatin: There is a risk of ototoxic effects when used with furosemide. There is also an increased risk of nephrotoxic effects unless furosemide is used at low doses (e.g. 40 mg in normal renal function) and with positive fluid balance during forced diuresis during cisplatin therapy.
Risperidone: Caution should be exercised and the risks and benefits carefully weighed before deciding on combination therapy with furosemide or other potent diuretics.
Sucralfate, cholestyramine, colestipol. Gastrointestinal absorption of furosemide is reduced, the concentration of furosemide in the blood and, accordingly, its effect are reduced. Therefore, these drugs and furosemide should be used with an interval of at least 2-3 hours.
ACE inhibitors/angiotensin-II receptor antagonists: Patients receiving diuretics may experience sudden severe hypotension and deterioration of renal function, including cases of renal failure, especially when first starting/first increasing the dose of ACE inhibitors/angiotensin-II receptor antagonists. It should be decided whether furosemide should be temporarily discontinued or at least the dose of furosemide should be reduced 3 days before starting/increasing the dose of ACE inhibitors/angiotensin-II receptor antagonists.
Combinations that require special attention.
If antihypertensive drugs, diuretics or other drugs that have the property of lowering blood pressure are used simultaneously with furosemide, a further decrease in blood pressure should be expected. The dosage of these drugs may need to be adjusted when used simultaneously with furosemide.
Alpha-blockers (e.g. prazosin, doxazosin, terazosin, tamsulosin). Increased hypotensive effect, risk of first-dose hypotension when used with furosemide. Increased risk of orthostatic hypotension.
Renin inhibitors: Aliskiren reduces the plasma concentration of furosemide.
Vasodilators. The hypotensive effect is enhanced, including moxifloxacin (thymoxamine), hydralazine, and nitrates.
Other diuretics: Significant increase in diuresis is possible when used with metolazone, increased risk of hypokalemia when combined with thiazides, increased risk of hyperkalemia with potassium-sparing diuretics (e.g., amiloride, spironolactone).
Drugs that prolong the QT interval (including antiarrhythmic drugs, antihistamines), cardiac glycosides, antipsychotics (e.g. pimozide, amisulpride, sertindole, phenothiazines). Diuretic-induced electrolyte disturbances, including hypokalemia, hypomagnesemia, increase the risk of toxic, including cardiotoxic effects of these drugs, the risk of cardiac arrhythmias, including torsades de pointes. The effects of lidocaine, tocainide, mexiletine may counteract the effects of furosemide. Combination with pimozide should be avoided. The hypotensive effect is increased when combined with phenothiazines. Drugs that do not have the property of provoking torsades de pointes arrhythmia in hypokalemia should be used.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid. The effect of furosemide is reduced, the risk of nephrotoxicity increases (especially in hypovolemia). In patients with dehydration/hypovolemia, NSAIDs can lead to acute renal failure. Furosemide may increase the toxicity of salicylates. Indomethacin and ketorolac may antagonize the effects of furosemide (it is advisable to avoid this combination if possible).
Nephrotoxic drugs (e.g. aminoglycosides, some high-dose cephalosporins, polymyxins). The toxic effects of these drugs may be increased by concomitant use of potent diuretics such as furosemide. Increased risk of hypokalemia and nephrotoxicity may occur with combination with amphotericin.
Antidepressants. Increased hypotensive effect when used with MAO inhibitors. Increased risk of orthostatic hypotension with tricyclic antidepressants. Increased risk of hypokalemia with reboxetine.
Antidiabetic drugs (including insulin), pressor amines (e.g. epinephrine, norepinephrine), allopurinol. Furosemide may reduce the effects of these drugs.
Antiepileptic drugs. Increased risk of hyponatremia when used with carbamazepine. The diuretic effect of furosemide is reduced by up to 50% when combined with phenytoin (higher doses of diuretic may be required).
Aminoglutethimide: Increased risk of hyponatremia.
Carbenoxolone, high-dose licorice root preparations, beta2-sympathomimetics, long-term use of stimulant laxatives. Increased risk of hypokalemia (additive effect), which requires monitoring. Do not use stimulant laxatives.
Corticosteroids, tetracosactide (systemic action). Sodium and fluid retention in the body and decreased antihypertensive effect are possible. Risk of hypokalemia.
Probenecid, methotrexate and other drugs that, like furosemide, undergo significant renal tubular secretion. The effectiveness of furosemide may be reduced. Conversely, furosemide may reduce the renal excretion of these drugs. High doses (of both furosemide and these drugs) may lead to increased serum levels and an increased risk of side effects of furosemide and the concomitant drug.
Immunomodulators. Cyclosporine, tacrolimus increase the risk of hyperkalemia. Concomitant use of cyclosporine is associated with an increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and impaired renal urate excretion caused by cyclosporine. Potentiation of the hypotensive effect of furosemide with aldesleukin.
Muscle relaxants (e.g. baclofen, tizanidine), general anesthetics, theophylline, levodopa, amifostine, anxiolytics and hypnotics, prostaglandins (e.g. alprostadil), alcohol. The hypotensive effect of furosemide is enhanced. Increased effects of curare-like muscle relaxants, theophylline.
Estrogens: Possible reduction of the diuretic effect of furosemide due to fluid retention in the body.
Progestogens (drospirenone). Increased risk of hyperkalemia.
Warfarin, clofibrate. Compete with furosemide for binding to serum albumin. May be important in hypoalbuminemia (e.g., nephrotic syndrome).
Metformin: Development of lactic acidosis due to possible functional renal failure associated with diuretics, and more specifically, with loop diuretics. Metformin should not be used when blood creatinine levels exceed 15 mg/L (135 μmol/L) in men and 12 mg/L (110 μmol/L) in women.
Radiocontrast agents: In patients at high risk for radiocontrast-induced nephropathy treated with furosemide, the use of radiocontrast agents without prior intravenous hydration increased the incidence of deterioration in renal function compared with patients at high risk who received intravenous hydration prior to the administration of radiocontrast agents.
Application features
During treatment with the drug, it is necessary to ensure constant urine outflow. Patients with partial obstruction of the urinary outflow tract require close attention, especially in the initial stages of treatment.
The use of furosemide requires regular medical and laboratory monitoring.
The condition should be monitored particularly closely and/or the dose should be reduced:
Elderly patients, who are particularly susceptible to side effects. Treatment should be started with low doses.
· patients with arterial hypotension;
· patients who are at risk due to a particular predisposition to a sharp decrease in blood pressure, for example, patients with severe stenosis of the coronary arteries or vessels supplying blood to the brain;
· patients with latent or manifest diabetes mellitus. In patients with diabetes mellitus, glycemic control may deteriorate; diabetes mellitus may progress from latent to manifest: an increase in the insulin dose may be necessary. Blood sugar levels should be monitored regularly. Furosemide should be discontinued before a glucose tolerance test;
· patients with gout. The use of furosemide slows down the excretion of uric acid and can provoke a gout attack; some diuretics are considered dangerous in acute porphyria;
· patients with impaired liver function. Liver failure and especially cirrhosis of the liver can provoke the development of hypokalemia and hypomagnesemia;
· patients with hepatorenal syndrome, i.e. with functional renal failure associated with severe liver disease;
· patients with hypoproteinemia due to nephrotic syndrome or cirrhosis of the liver (reduction of the effects of furosemide with simultaneous potentiation of its ototoxicity). Careful dose titration is necessary;
· premature infants (possible development of nephrocalcinosis/nephrolithiasis); renal function should be monitored and renal ultrasonography performed.
In the presence of dropsy without peripheral edema, the drug is recommended to be used in doses that provide additional diuresis in a volume of no more than 700-900 ml/day, which does not cause significant changes in blood plasma ion indices, residual nitrogen, and helps prevent oliguria.
If oliguria persists for 24 hours, treatment with the drug should be discontinued.
When treating arterial hypertension, the daily dose should be divided into 2-3 doses, which makes it possible to avoid the development of the "rebound" phenomenon.
During furosemide therapy, especially long-term therapy, periodic measurement of blood pressure, regular monitoring of serum sodium, potassium, calcium, chlorine, magnesium, uric acid and creatinine levels is recommended, especially in patients at high risk of developing electrolyte imbalance or in case of significant fluid loss (e.g. as a result of vomiting, diarrhea or intense sweating). Hypovolemia or dehydration, electrolyte and acid-base imbalances should be corrected; temporary discontinuation of furosemide is possible.
The development of electrolyte imbalances is influenced by factors such as existing diseases (e.g., cirrhosis, heart failure), concomitant medication use, and dietary habits. For example, potassium deficiency may occur as a result of vomiting or diarrhea.
In placebo-controlled trials of risperidone in elderly patients with dementia, a higher mortality rate was observed in patients receiving furosemide concomitantly with risperidone compared to patients receiving risperidone or furosemide alone. Caution should be exercised and the risks and benefits carefully weighed before deciding to use risperidone with furosemide or other potent diuretics. Dehydration should be avoided.
The simultaneous use of alcohol and furosemide should be avoided.
Photosensitivity reactions have been reported with furosemide. If they occur, discontinuation of the drug is recommended. If furosemide is to be re-administered, exposed skin should be protected from the sun or artificial UV radiation.
Athletes should be aware that the use of furosemide may lead to a positive result during doping control.
The drug contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use it.
Use during pregnancy or breastfeeding
Furosemide crosses the placental barrier and should not be used during pregnancy unless absolutely necessary. Treatment with the drug during pregnancy requires monitoring of fetal growth and development.
Furosemide passes into breast milk and may inhibit lactation. Breastfeeding should be discontinued during treatment with the drug.
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 vehicles or other mechanisms.
Method of administration and doses
Furosemide is usually taken orally on an empty stomach. The dosage regimen is set by the doctor individually according to the severity of the water-electrolyte imbalance, the value of glomerular filtration, the severity of the patient's condition. During treatment, the indicators of water-electrolyte balance should be adjusted taking into account diuresis and the dynamics of the patient's general condition.
The lowest effective dose should be used. Furosemide has a wide therapeutic range and its effects are dose-proportional.
Adults: The maximum daily dose of furosemide is 1500 mg.
Children. The drug in this dosage form should be prescribed to children weighing more than 10 kg. The recommended oral dose of furosemide for children is 2 mg/kg of body weight, but the maximum daily dose should not exceed 40 mg.
Special dosage recommendations for adults.
Edema in chronic congestive heart failure. The recommended initial dose of the drug is 20-40 mg per day. If necessary, the dose can be adjusted depending on the patient's therapeutic response. It is recommended to divide the daily dose into 2-3 doses.
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. 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+).
The recommended initial oral dose is 40-80 mg per day. The dose may be adjusted as necessary based on the patient's response. The total daily dose may be administered as a single dose or in two divided doses.
For patients on hemodialysis, the total daily oral dose is 250-1500 mg.
Acute renal failure. Before starting Furosemide, hypovolemia, arterial hypotension and significant electrolyte and acid-base imbalance should be compensated. It is recommended to switch from intravenous administration to oral administration of the drug as soon as possible.
Edema in nephrotic syndrome. The recommended initial oral dose is 40-80 mg per day. The dose may be adjusted as necessary based on the patient's response. The total daily dose may be administered as a single dose or in divided doses.
Edema in liver disease. Furosemide should be administered as an adjunct to aldosterone antagonist therapy when aldosterone antagonist therapy alone is insufficient. To avoid complications such as orthostatic hypotension or electrolyte and acid-base imbalance, the dose should be titrated carefully to ensure a gradual initial fluid loss. For adult patients, this means using a dose that results in a daily weight loss of approximately 0.5 kg. The recommended initial oral dose is 20-40-80 mg per day. The dose can be adjusted as necessary depending on the patient's therapeutic response. The total daily dose can be administered as a single dose or in divided doses.
Elderly patients. Should be used with caution, as furosemide elimination is slowed in these patients. Treatment should be initiated with 20 mg and the dose increased if necessary.
If it is necessary to prescribe the drug in a dose of 20 mg, furosemide preparations with the possibility of such a dosage should be used.
Children
The drug should not be used in children weighing less than 10 kg. The recommended oral dose of furosemide for children is 2 mg/kg body weight, the maximum daily dose should not exceed 40 mg.
For children who cannot use the tablet form (e.g., premature infants, neonates), the parenteral form should be considered.
Overdose
The clinical picture of acute or chronic overdose depends mainly on the extent and consequences of electrolyte and fluid loss.
Symptoms: hypovolemia, dehydration, hemoconcentration, electrolyte imbalance (including hypokalemia and hypochloremic alkalosis) due to the diuretic effect, cardiac arrhythmias (including AV block and ventricular fibrillation), severe arterial hypotension (may progress to shock), orthostatic collapse, acute renal failure, thrombosis, delirium, peripheral paralysis, apathy and confusion.
Treatment: discontinuation of the drug, in case of recent intake - induction of vomiting, gastric lavage, use of activated charcoal to limit further absorption, correction of water and electrolyte balance, restoration of BCC, symptomatic therapy. There is no specific antidote.
Adverse reactions
Metabolic disorders.
Electrolyte disturbances (including symptomatic), especially in patients receiving high doses of furosemide for a long period: hyponatremia, hypochloremia, hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis. Symptomatic electrolyte disturbances and metabolic alkalosis may lead to gradually increasing electrolyte deficits or, when higher doses are used in patients with normal renal function, to acute significant electrolyte loss and a sharp deterioration in the condition.
Excessive diuresis can lead to dehydration and hypovolemia, especially in elderly patients and children.
Increased levels of creatinine, urea, triglycerides in the blood, hypercholesterolemia.
Increased uric acid levels in the blood and risk of gout flare-ups.
Hyperglycemia, impaired glucose tolerance, which may lead to worsening of glycemic control in patients with diabetes mellitus; manifestation of latent diabetes mellitus is possible. With prolonged use of diuretics, the development of hyperosmolar coma is possible.
Pseudo-Bartter syndrome when using too high doses for a long time.
Blood and lymphatic system.
Significant fluid loss can lead to hemoconcentration with a tendency to increase blood clotting processes and thrombosis, especially in elderly patients.
Thrombocytopenia with potentially increased bleeding tendency.
Leukopenia, eosinophilia.
Bone marrow depression, aplastic anemia, hemolytic anemia, agranulocytosis with increased susceptibility to infections. Hematopoietic status should be monitored regularly.
Immune system.
Allergic reactions, severe anaphylactic reactions, including anaphylactic shock, and anaphylactoid reactions.
Skin and subcutaneous tissue.
Pruritus, urticaria, bullous reactions, including bullous pemphigoid, other types of rashes, exudative erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis and Stevens-Johnson syndrome, purpura, AGEP syndrome (acute generalized exanthematous pustulosis), DRESS syndrome (drug hypersensitivity syndrome with systemic symptoms), in some cases - photosensitization.
Cardiovascular system.
Arrhythmias, arterial hypotension, including orthostatic hypotension, vasculitis, including necrotizing vasculitis, thrombosis.
Urinary system.
Increased urine production can provoke or aggravate any difficulty in urine outflow (including in case of prostatic hyperplasia or urethral narrowing, in case of bladder pathology), acute urinary retention is possible in patients with partial urinary tract obstruction.
Tubulointerstitial nephritis, renal failure. Possible decreased diuresis, urinary incontinence. Potassium deficiency may manifest as renal symptoms such as polyuria and polydipsia.
Premature infants may develop nephrocalcinosis/nephrolithiasis.
Increased levels of sodium and chlorine in the urine.
Digestive system.
Decreased appetite/anorexia, irritation of the oral and gastric mucosa, dry mouth, thirst, flatulence, colic, intestinal motility disorders/intestinal obstruction (in severe hypokalemia), nausea, vomiting, diarrhea/constipation, acute pancreatitis.
Hepatobiliary system.
Intrahepatic cholestasis, jaundice, increased levels of hepatic transaminases in the blood, hepatic encephalopathy in patients with hepatocellular insufficiency.
Nervous system.
Headache/feeling of pressure in the head, dizziness, vertigo, depression, paresthesias, decreased concentration, confusion, drowsiness, weakness, delirium.
Transient short-term hearing loss, tinnitus, especially in patients with renal insufficiency, hypoproteinemia (e.g. nephrotic syndrome) and/or in case of too rapid intravenous administration of furosemide (for parenteral form). Cases of deafness, sometimes irreversible, have been reported.
Visual disturbances, including blurred vision, xanthopsia.
Musculoskeletal system.
Muscle weakness, possible partial or complete paralysis, muscle spasms/convulsions, tetany.
General disorders.
Feeling tired, malaise, fever.
Congenital, hereditary and genetic disorders.
Increased risk of non-closure of the patent ductus arteriosus in premature infants with respiratory distress syndrome when furosemide is administered in the first weeks of life.
Expiration date
4 years.
Do not use the drug after the expiration date indicated on the package!
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister, 5 blisters in a pack.
Vacation category
According to the recipe.
Manufacturers
Public Joint Stock Company "Research and Production Center "Borshchagov Chemical and Pharmaceutical Plant".
Limited Liability Company "Agropharm".
Location of manufacturers and their business addresses
Ukraine, 03134, Kyiv, Myru St., 17.
Ukraine, 08200, Kyiv region, Irpin, Centralna st., 113-A.
