INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FUROSEMIDE (FUROSEMIDE)

Composition:

Active substance: furosemide;

One tablet contains furosemide, calculated as 100 % substance – 40 mg;

Excipients: lactose monohydrate; magnesium stearate; potato starch.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets are white, almost white, or white with a creamy shade, round-shaped with a flat surface and a bevel edge.

Pharmacotherapeutic group.

High-ceiling diuretics. Simple sulfonamide agents. Furosemide. ATC code C03C A01.

Pharmacological properties.

Pharmacodynamics.

Furosemide is a potent, rapid-acting loop diuretic. It produces a relatively strong and short-lived diuretic effect. By blocking the Na+/2Cl-/K+ ion transporter, the drug inhibits reabsorption of these ions in the ascending limb of the loop of Henle. Thus, the saluretic efficacy of furosemide depends on whether the drug reaches the tubular lumen via an anion-transport mechanism. The diuretic effect results from inhibition of sodium chloride reabsorption in this segment of the loop of Henle. As a result, fractional excretion of sodium may reach up to 35% of the glomerular filtration of sodium. Increased sodium excretion leads to increased urine output and enhanced secretion of K+ in the distal tubules due to osmotically bound water. Excretion of calcium and magnesium ions is also increased. In addition to excretion of these electrolytes, a possible decrease in uric acid excretion and disturbance of acid-base balance may occur, potentially leading to metabolic alkalosis.

Furosemide disrupts the tubuloglomerular feedback mechanism at the macula densa, thereby maintaining its saluretic efficacy.

Furosemide induces dose-dependent stimulation of the renin–angiotensin–aldosterone system. In heart failure, furosemide causes acute reduction of cardiac preload (by constricting capacitance venous vessels). This early vascular effect is prostaglandin-mediated and requires adequate renal function with activation of the renin–angiotensin system and intact prostaglandin synthesis. Additionally, due to its intrinsic natriuretic effect, furosemide reduces vascular smooth muscle reactivity to catecholamines, which is elevated in patients with arterial hypertension.

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

The onset of diuretic effect occurs within 1 hour after oral administration of the drug.

Dose-dependent increases in diuresis and natriuresis have been observed in healthy subjects receiving furosemide at doses of 10–100 mg. The duration of action in healthy individuals is approximately 3–6 hours after oral administration of 40 mg furosemide.

The effect of furosemide diminishes if there is reduced tubular secretion or drug interaction with albumin within the tubules.

Furosemide reduces blood pressure by increasing excretion of sodium chloride, reducing vascular smooth muscle response to vasoconstrictor stimulation, and decreasing blood volume.

Pharmacokinetics.

After oral administration, approximately 60–70% of the furosemide dose is absorbed in the gastrointestinal tract. In patients with chronic heart failure or nephrotic syndrome, absorption may decrease to less than 30%.

Onset of action can be expected approximately 30 minutes after administration. Maximum plasma concentration is reached approximately 1 hour after oral administration of furosemide in tablet form.

Furosemide is approximately 95% bound to plasma proteins. In renal impairment, protein binding may decrease by up to 10%. The apparent volume of distribution is about 0.2 L/kg body weight (in newborns, 0.8 L/kg body weight).

Furosemide is only minimally metabolized in the liver (approximately 10%) and is primarily excreted unchanged. Two-thirds of the dose is excreted by the kidneys and one-third via bile and feces. With normal renal function, the elimination half-life is approximately 1 hour. In end-stage renal failure, it may be prolonged up to 24 hours.

Clinical characteristics.

Indications.

Edema in chronic congestive heart failure (if treatment with diuretics is required).
Edema in chronic renal failure.
Acute renal failure (including in pregnant women or during labor).
Edema in nephrotic syndrome (if treatment with diuretics is required).
Edema in liver diseases (if necessary, to supplement treatment with aldosterone antagonists).
Arterial hypertension.

Contraindications.

Hypersensitivity to furosemide or to any of the excipients of the drug. Cross-sensitivity to furosemide may occur in patients with allergy to sulfonamides (e.g., sulfonamide antibiotics or sulfonylureas).
Hypovolemia or dehydration.
Renal failure manifested as anuria unresponsive to furosemide therapy.
Renal failure due to poisoning with nephrotoxic or hepatotoxic agents.
Severe hypokalemia.
Severe hyponatremia.
Pre-comatose or comatose states associated with hepatic encephalopathy.
Breastfeeding.
Pregnancy (except for cases specified in the section "Indications").

Interaction with other medicinal products and other forms of interactions.

Not recommended combinations.

After intravenous administration of furosemide within 24 hours following chloral hydrate use, sensations of warmth, sweating attacks, restlessness, nausea, increased blood pressure, and tachycardia may occur in individual cases. Therefore, concomitant use of furosemide and chloral hydrate should be avoided.

Concomitant use of furosemide may enhance the ototoxicity of aminoglycosides (e.g., kanamycin, gentamicin, tobramycin) and other ototoxic medicinal products. Any hearing disturbances that may occur under these conditions can be irreversible. Therefore, concomitant use of the above-mentioned medicinal products should be avoided.

Combinations requiring precautions.

Concomitant use of cisplatin and furosemide may lead to hearing impairment. If forced diuresis is attempted during cisplatin therapy, furosemide should be administered only at low doses (e.g., 40 mg in patients with normal renal function) and provided there is a positive fluid balance. Otherwise, the nephrotoxicity of cisplatin may be enhanced.

Since sucralfate reduces intestinal absorption of furosemide, thereby diminishing its effect, an interval of at least 2 hours should be maintained between administration of these two medicinal products.

Aliskiren reduces plasma concentrations of furosemide when administered orally. When used concomitantly with aliskiren, monitoring of the diuretic effect of furosemide is recommended at the beginning of treatment and during dose adjustments.

Hypokalemia and/or hypomagnesemia induced by furosemide increase myocardial sensitivity to cardiac glycosides when used concomitantly. The risk of ventricular arrhythmias (including torsades de pointes) is increased if furosemide is used concomitantly with medicinal products that may prolong the QT interval (e.g., terfenadine, certain class I and III antiarrhythmics), especially in the presence of electrolyte disturbances in the patient.

Toxicity of salicylates administered in high doses may be potentiated when used concomitantly with furosemide.

Concomitant use of furosemide and lithium enhances cardiac and neurotoxic effects of lithium due to reduced lithium excretion. Therefore, careful monitoring of plasma lithium levels is recommended in patients receiving this combination.

If furosemide is used concomitantly with other antihypertensive agents, diuretics, or medicinal products with potential blood pressure-lowering effects, a more pronounced reduction in blood pressure should be expected.

Significant drops in blood pressure or even shock and worsening of renal function (in some cases, acute renal failure) have been observed, particularly when angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists are initiated or first used at higher doses. Therefore, whenever possible, furosemide should be temporarily discontinued or at least the dose reduced three days before starting treatment with an ACE inhibitor or angiotensin II receptor antagonist, or before increasing their doses.

Caution and careful assessment of risks versus benefits are required when considering concomitant use of risperidone with furosemide or other potent diuretics (see section "Special precautions" for information on increased mortality in elderly patients with dementia receiving risperidone).

Levothyroxine. High doses of furosemide may inhibit thyroid hormone binding to carrier proteins, leading initially to a transient increase in free thyroid hormone fractions, followed by an absolute decrease in all thyroid hormone fractions.

Thyroid hormone levels should be monitored.

Combinations that should be considered.

Nonsteroidal anti-inflammatory drugs (e.g., indomethacin, acetylsalicylic acid) may reduce the effect of furosemide. In patients who develop hypovolemia or dehydration during furosemide therapy, concomitant use of nonsteroidal anti-inflammatory drugs may precipitate acute renal failure.

Concomitant use of furosemide with glucocorticoids, carbenoxolone, or laxatives may lead to increased potassium deficiency, increasing the risk of hypokalemia. In this regard, large amounts of licorice act similarly to carbenoxolone.

Probenecid, methotrexate, and other medicinal products that, like furosemide, undergo significant tubular secretion in the kidneys, may reduce the effect of furosemide.

Cases of reduced furosemide effect have been reported with concomitant use of phenytoin.

Furosemide may reduce renal excretion of probenecid, methotrexate, and other medicinal products that, like furosemide, undergo significant tubular secretion. In treatment involving high doses (especially when both furosemide and the other medicinal product are used at high doses), such combination may lead to increased serum levels of these drugs and an increased risk of adverse effects caused by furosemide or the concomitantly administered medicinal product.

Furosemide may enhance the effect of theophylline or curare-like muscle relaxants.

The effect of antidiabetic agents and sympathomimetics that increase blood pressure (e.g., adrenaline, noradrenaline) may be reduced when used concomitantly with furosemide.

Furosemide may potentiate the harmful effects of nephrotoxic medicinal products (e.g., antibiotics such as aminoglycosides, cephalosporins, polymyxins).

In patients receiving furosemide concomitantly with high doses of certain cephalosporins, worsening of renal function is possible.

Other types of interactions

Concomitant use of cyclosporine A and furosemide is associated with an increased risk of gouty arthritis due to furosemide-induced hyperuricemia and impaired renal excretion of uric acid caused by cyclosporine.

In patients at high risk of kidney injury from radiographic contrast agents, treatment with furosemide has been associated with a higher frequency of worsening renal function after contrast examinations compared to patients in the high-risk group who received only intravenous fluid (hydration) prior to contrast procedures.

Special precautions for use.

During treatment with Furosemide, continuous urine outflow must be ensured. Patients with partial obstruction of urinary outflow require close monitoring, especially during the initial stages of therapy.

Treatment with Furosemide requires regular medical supervision.

Special caution is necessary in the following situations:

arterial hypotension,
overt or latent diabetes mellitus (regular monitoring of blood glucose levels is required),
gout (regular monitoring of serum uric acid levels is required),
impaired urinary excretion (e.g., due to benign prostatic hyperplasia, hydronephrosis, ureteral stenosis),
hypoproteinemia, for example in nephrotic syndrome (careful dose adjustment is required),
hepatorenal syndrome (rapidly progressive renal failure associated with severe liver disease, such as hepatic cirrhosis),
patients belonging to a high-risk group for significant drop in arterial pressure, e.g., patients with cerebral circulation disorders or ischemic heart disease,
premature infants (risk of developing nephrocalcinosis/nephrolithiasis; monitoring of renal function and ultrasound examination of kidneys is required).

Symptomatic hypotension, leading to dizziness, fainting, or loss of consciousness, may occur in patients receiving furosemide, particularly in elderly patients, patients taking other medications that may cause hypotension, and patients with other conditions predisposing to hypotension.

Furosemide should be administered to patients with impaired urinary excretion (e.g., due to benign prostatic hyperplasia) only when free urine outflow is ensured, as a sudden increase in urine production may lead to urinary retention with overdistension of the urinary bladder.

Furosemide increases the excretion of sodium and chloride, and consequently water. Excretion of other electrolytes (especially potassium, calcium, and magnesium) is also enhanced. Since disturbances in water-electrolyte balance frequently occur during treatment with Furosemide due to increased electrolyte excretion, serum electrolyte levels must be monitored regularly.

Regular monitoring of serum electrolytes (especially potassium, sodium, calcium), bicarbonates, creatinine, urea, and uric acid, as well as blood glucose levels, is required, particularly during prolonged treatment with Furosemide.

Particularly careful monitoring is necessary for patients at high risk of electrolyte imbalance and patients with significant fluid deficit (e.g., due to vomiting, diarrhea, or excessive sweating). Hypovolemia or dehydration, as well as any pronounced disturbances in electrolyte and acid-base balance, should be corrected. This may require temporary discontinuation of furosemide therapy.

The development of electrolyte imbalances may be influenced by pre-existing conditions (such as hepatic cirrhosis, heart failure), concomitant use of medications (see section "Interaction with other medicinal products and other forms of interaction"), and diet.

Weight loss due to enhanced diuresis should not exceed 1 kg per day, regardless of the volume of urine excreted.

In nephrotic syndrome, dose selection should be carefully considered due to the risk of increased adverse effects.

Concomitant use with risperidone.

In placebo-controlled studies using risperidone in elderly patients with dementia, a higher mortality rate was observed in the group receiving both furosemide and risperidone (7.3%; mean age 89 years, age range 75–97 years) compared to groups receiving only risperidone (3.1%; mean age 84 years, age range 70–96 years) or only furosemide (4.1%; mean age 80 years, age range 67–90 years). Concomitant use of risperidone with other diuretics (mostly low-dose thiazide diuretics) did not lead to similar results.

No pathophysiological mechanism has been identified to explain these data, and no patterns regarding the causes of death in these patients have been observed. However, caution should be exercised and risks and benefits carefully weighed before deciding to use this combination or concomitant treatment with other potent diuretics. In the group of patients who received other diuretics concomitantly with risperidone, no increased mortality was observed. Regardless of treatment, dehydration was a common risk factor for mortality; therefore, dehydration should be avoided when treating elderly patients with dementia (see section "Contraindications").

There is a possibility of exacerbation or activation of systemic lupus erythematosus.

Administration of Furosemide may lead to positive doping test results. Moreover, misuse of Furosemide as a doping agent may be hazardous to health.

Warnings regarding specific excipients.

Patients with rare hereditary disorders of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take Furosemide.

Use during pregnancy or breastfeeding.

Pregnancy. Furosemide crosses the placental barrier and therefore should be used during pregnancy only for short periods and only after careful consideration of the necessity of such treatment (see section "Indications"). Diuretics are not appropriate for routine treatment of arterial hypertension and edema during pregnancy, as they impair placental circulation and, consequently, fetal intrauterine development.

However, if furosemide must be prescribed due to renal insufficiency in a pregnant woman, serum electrolyte and hematocrit levels, as well as fetal development, should be closely monitored. Displacement of bilirubin from its binding sites on albumin has been reported with furosemide use, increasing the risk of kernicterus in newborns in cases of hyperbilirubinemia.

Furosemide crosses the placental barrier, and its concentration in umbilical cord blood reaches 100% of the maternal serum concentration. To date, no congenital malformations in humans have been definitively linked to furosemide use. However, there are insufficient data to draw definitive conclusions regarding possible harmful effects on the embryo/fetus. Intrauterine stimulation of fetal urine production is possible. Cases of urolithiasis have been observed in premature infants who received furosemide.

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

Ability to affect performance when driving or operating machinery.

Some adverse effects (such as unexpected significant drop in arterial pressure) may impair a patient's ability to concentrate and reaction speed; therefore, patients should refrain from driving vehicles or operating machinery during treatment.

Dosage and Administration

The dosage regimen should be determined individually by a physician, depending on the severity of water-electrolyte imbalance, glomerular filtration rate, and the patient's clinical condition. During treatment, water-electrolyte parameters should be adjusted according to diuresis and the patient’s overall clinical progress. The lowest effective dose that provides the desired therapeutic effect should always be used. The medicinal product should be taken on an empty stomach, swallowing the tablets whole with sufficient fluid (e.g., one glass of water).

Special Dosage Recommendations

Acute Renal Failure

Before initiating furosemide therapy, hypovolemia, arterial hypotension, and significant electrolyte or acid-base imbalances must be corrected. Transition from intravenous to oral administration should be made as soon as possible.

Edema in Chronic Congestive Heart Failure / Edema in Liver Disease / Edema in Chronic Renal Failure

The usual initial dose in adults corresponds to 1 tablet of the medicinal product (equivalent to 40 mg of furosemide). If adequate diuresis is not achieved, a double dose—2 tablets (equivalent to 80 mg of furosemide)—may be administered once after 6 hours. If satisfactory diuresis is still not achieved, 4 tablets (equivalent to 160 mg of furosemide) may be taken after another 6 hours. In exceptional cases and under strict clinical monitoring, initial doses exceeding 200 mg of furosemide may be used.

The usual daily maintenance dose corresponds to 1–2 tablets of the medicinal product (equivalent to 40–80 mg of furosemide). Weight loss due to increased diuresis should not exceed 1 kg per day.

Edema in Nephrotic Syndrome

The recommended initial oral dose is 40–80 mg daily. If necessary, the dose may be adjusted according to the patient's therapeutic response. The total daily dose may be taken as a single dose or divided into several doses.

Arterial Hypertension

The usual dose is 1 tablet of the medicinal product (equivalent to 40 mg of furosemide) once daily, either as monotherapy or in combination with other medicinal products.

For children unable to take oral dosage forms (e.g., premature infants and newborns), parenteral formulations should be considered.

For children, the recommended oral dose of furosemide is up to 2 mg/kg body weight, but the maximum daily dose should not exceed 40 mg. The dose should be adjusted according to body weight.

Children

This medicinal product in the given dosage form should be prescribed only to children with body weight above 10 kg. The recommended daily oral dose of furosemide for children is 2 mg/kg body weight. The maximum daily dose in children should not exceed 40 mg.

For children unable to take oral dosage forms (e.g., premature infants and newborns), parenteral formulations should be considered.

Overdose

Symptoms: The clinical picture of acute or chronic overdose primarily depends on the degree and consequences of fluid and electrolyte loss.

Overdose may lead to arterial hypotension, orthostatic disturbances, electrolyte imbalances (hypokalemia, hyponatremia, hypochloremia), or alkalosis. In cases of severe fluid deficit, marked hypovolemia, dehydration, circulatory collapse, and hemoconcentration with a tendency toward thrombosis may occur. Delirium may occur with rapid fluid and electrolyte losses. In rare cases, anaphylactic shock may develop (symptoms: sweating, nausea, cyanosis, marked drop in arterial pressure, impaired consciousness, or even coma).

Treatment

In case of overdose or development of signs of hypovolemia (arterial hypotension, orthostatic disturbances), furosemide must be discontinued immediately.

If only a short time has passed since oral intake of furosemide, measures to eliminate initial intoxication are recommended (induce vomiting, gastric lavage) and to reduce drug absorption (activated charcoal).

In more severe cases, vital signs must be monitored, and repeated assessment of fluid and electrolyte balance, acid-base balance, blood glucose, and urinary excretion of substances should be performed, with correction of any identified abnormalities as needed.

In patients with impaired urinary excretion (e.g., due to benign prostatic hyperplasia), free urine passage must be ensured, as a sudden increase in urine production may lead to urinary retention and bladder overdistension.

Treatment of hypovolemia: fluid infusion.

Treatment of hypokalemia: potassium replacement therapy.

Treatment of circulatory collapse: the patient should be placed in anti-shock position; anti-shock therapy should be administered if necessary.

Emergency measures in case of anaphylactic shock at the first signs (e.g., skin reactions such as urticaria or hyperemia, restlessness, headache, sweating attacks, nausea, cyanosis):

Ensure intravenous access.
In addition to standard emergency measures, place the patient in a horizontal supine position with elevated lower limbs, ensure airway patency, and administer oxygen.
If necessary, implement other intensive care emergency measures (including administration of adrenaline, plasma substitutes, glucocorticoids).

Adverse Reactions

The frequency of adverse reactions is based on published references to study data in which furosemide was administered to a total of 1387 patients at any dose and for any indication. When the same adverse reaction was reported in different frequency categories across different sources, the highest frequency category was selected. Where possible, the following CIOMS criteria were applied to classify adverse reactions by frequency: very common (≥ 10%); common (≥ 1% to < 10%); uncommon (≥ 0.1% to < 1%); rare (≥ 0.01% to < 0.1%); very rare (< 0.01%); frequency not known (cannot be estimated from available data).

Metabolic and nutritional disorders

Very common: electrolyte imbalance (including symptomatic manifestations), dehydration and hypovolemia (particularly in elderly patients), increased triglyceride levels.

Common: hyponatremia, hypochloremia (especially in patients with restricted sodium chloride intake), hypokalemia (particularly in patients with concomitant reduced potassium intake and/or increased potassium loss from the body, e.g., due to vomiting or chronic diarrhea), increased blood cholesterol levels, increased blood uric acid levels, gout attacks.

Uncommon: impaired glucose tolerance and hyperglycemia. In patients with overt diabetes mellitus, this may lead to worsening of metabolic status. Latent diabetes mellitus may progress to overt disease (see section "Special precautions").

Frequency not known: hypocalcemia, hypomagnesemia, metabolic alkalosis, pseudo-Bartter syndrome due to incorrect and/or prolonged use of furosemide.

Common symptoms of sodium deficiency include apathy, calf muscle cramps, loss of appetite, weakness, drowsiness, vomiting, and confusion.

Hypokalemia may manifest as neuromuscular signs (muscle weakness, paresthesia, paresis), gastrointestinal signs (vomiting, constipation, flatulence), renal signs (polyuria, polydipsia), and cardiac signs (disturbances in myocardial impulse generation and conduction). Severe potassium deficiency may lead to paralytic ileus, disturbances of consciousness, or even coma.

Hypocalcemia may rarely cause tetany.

Rare cases of tetany or development of cardiac arrhythmias due to hypomagnesemia have been observed.

Vascular system

Very common (with administration of the drug in the appropriate dosage form by intravenous infusion): arterial hypotension, including orthostatic arterial hypotension (see section "Special precautions").

Rare: vasculitis.

Frequency not known: thrombosis (particularly in elderly patients).

Circulatory disturbances (even circulatory collapse) may occur with excessive diuresis, especially in children and elderly patients, manifesting primarily as headache, dizziness, visual disturbances, dry mouth, thirst, arterial hypotension, and orthostatic disorders.

Renal and urinary disorders

Very common: increased blood creatinine levels.

Common: increased urine volume.

Rare: tubulointerstitial nephritis.

Frequency not known:

increased urinary sodium levels, increased urinary chloride levels, increased blood urea levels, symptoms of impaired urination (e.g., in patients with prostate hyperplasia, hydronephrosis, ureteral stenosis), up to urinary retention with development of secondary complications (see section "Special precautions");
nephrocalcinosis and/or nephrolithiasis in premature infants (see section "Special precautions");
renal failure (see section "Interaction with other medicinal products and other forms of interaction").

Gastrointestinal disorders

Uncommon: nausea.

Rare: vomiting, diarrhea.

Very rare: acute pancreatitis.

Hepatobiliary disorders

Very rare: intrahepatic cholestasis, increased transaminase levels.

Auditory and vestibular disorders

Uncommon: hearing disturbances, which are usually transient, particularly in patients with renal insufficiency, hypoproteinemia (e.g., in nephrotic syndrome), and/or in cases of too rapid intravenous administration of furosemide. Cases of deafness, sometimes irreversible, have been reported.

Rare: tinnitus.

Skin and subcutaneous tissue disorders

Uncommon: pruritus, urticaria, rash, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, photosensitivity reaction.

Frequency not known: Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP), and DRESS syndrome (drug reaction with eosinophilia and systemic symptoms).

Immune system disorders

Uncommon: allergic reactions affecting the skin and mucous membranes (see "Skin and subcutaneous tissue disorders").

Rare: severe anaphylactic or anaphylactoid reactions, e.g., anaphylactic shock (treatment information see section "Overdose"). Initial signs of shock include skin reactions such as hyperemia or urticaria, restlessness, headache, sweating, nausea, cyanosis.

Frequency not known: exacerbation or activation of systemic lupus erythematosus.

Nervous system disorders

Common: hepatic encephalopathy in patients with hepatic insufficiency (see section "Contraindications").

Rare: paresthesia.

Frequency not known: dizziness, syncope, loss of consciousness, and headache.

Blood and lymphatic system disorders

Common: hemoconcentration (due to excessive diuresis).

Uncommon: thrombocytopenia.

Rare: leukopenia, eosinophilia.

Very rare: agranulocytosis, aplastic anemia, or hemolytic anemia. Signs of agranulocytosis may include fever with chills, mucosal changes, and sore throat.

Musculoskeletal and connective tissue disorders

Frequency not known: cases of rhabdomyolysis have been reported, often in the context of severe hypokalemia (see section "Contraindications").

Congenital and hereditary/genetic disorders

Frequency not known: increased risk of failure of arterial duct closure if furosemide is administered to premature infants during the first weeks of life.

General disorders and administration site conditions

Rare: increased body temperature.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after medicinal product registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 10 tablets per blister, 5 blisters per pack.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and place of business.

139 Saksahanskoho St., Kyiv, 01032, Ukraine.