INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LASIX® (LASIX®)

Composition:

Active substance: furosemide;

1 tablet contains 40 mg of furosemide;

Excipients: lactose monohydrate, maize starch, pregelatinized starch, talc, colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white, round tablets with the letter code "DLI" imprinted above and below the break line on one side.

Pharmacotherapeutic group.

High-ceiling diuretics. Sulfonamide agents. ATC code C03CA01.

Pharmacological Properties

Pharmacodynamics

Furosemide is a potent, rapidly-acting loop diuretic that 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 Henle's loop; 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 Henle's loop. The fractional excretion of sodium may reach up to 35% of the amount of sodium filtered through the glomeruli. Increased sodium excretion leads to enhanced water elimination in urine and increased K+ secretion in the distal tubules due to osmotically-bound water. Excretion of calcium and magnesium ions is also increased. In addition to these electrolyte losses, reduced excretion of uric acid and disturbances in 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 an acute reduction in 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 inherent natriuretic effect, furosemide reduces vascular reactivity to catecholamines, which is heightened in patients with arterial hypertension.

The antihypertensive efficacy of furosemide is explained by increased sodium excretion, reduced blood volume, and decreased vascular smooth muscle responsiveness to vasoconstrictor stimuli or vasoconstricting agents.

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

Dose-dependent increases in diuresis and natriuresis have been observed in healthy volunteers 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, decreasing vascular smooth muscle response to vasoconstrictor stimulation, and reducing 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 intake of Lasix**®** tablets.

Furosemide is approximately 95% bound to plasma proteins. In renal insufficiency, 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 during pregnancy or childbirth.
Edema in nephrotic syndrome (if treatment with diuretics is required).
Edema in liver diseases (if necessary, as adjunctive therapy with aldosterone antagonists).
Arterial hypertension.

Contraindications.

Hypersensitivity to furosemide or to any other components of the medicinal product. Cross-sensitivity to furosemide may occur in patients with allergy to sulfonamides (e.g., sulfonamide antibiotics or sulfonylureas).
Hypovolemia or dehydration.
Renal failure manifesting as anuria unresponsive to furosemide therapy.
Renal failure due to 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 interaction.

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 may 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 in low doses (e.g., 40 mg in patients with normal renal function) and only if fluid balance is positive. 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. Reduced furosemide effect may occur in patients receiving both aliskiren and oral furosemide; therefore, monitoring for reduced diuretic effect is recommended, and dosage adjustments should be made accordingly. Monitoring of furosemide's diuretic effect is recommended when initiating or adjusting aliskiren therapy.

Hypokalemia and/or hypomagnesemia induced by furosemide increases myocardial sensitivity to cardiac glycosides when used concomitantly. An increased risk of ventricular arrhythmias (including torsades de pointes) may occur when 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.

Toxicity of high-dose salicylates may be potentiated when administered concomitantly with furosemide.

Concomitant use of furosemide and lithium may enhance 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.

Cases of significant drop in blood pressure or even shock and worsening of renal function (in some cases, acute renal failure) have been observed, particularly when an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor antagonist is initiated or first used at higher doses. Therefore, if possible, furosemide should be temporarily discontinued or at least the dose reduced three days prior to initiating treatment with an ACE inhibitor or angiotensin II receptor antagonist or prior to increasing their doses.

Caution and careful assessment of risks and benefits are required before deciding to use risperidone in combination 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 binding of thyroid hormones to carrier proteins, thus initially causing a transient increase in free fractions of thyroid hormones, followed by an absolute decrease in levels of all thyroid hormone fractions.

Thyroid hormone levels should be monitored.

Combinations to 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 treatment, concomitant use of nonsteroidal anti-inflammatory drugs may trigger the development of acute renal failure.

Concomitant use of furosemide with glucocorticoids, carbenoxolone, or laxatives may lead to enhanced potassium deficiency, increasing the risk of hypokalemia. In this regard, large amounts of licorice exert effects similar to carbenoxolone.

Probenecid, methotrexate, and other medicinal products that, like furosemide, undergo significant tubular secretion, 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 with high doses (especially when both furosemide and the other medicinal product are administered at high doses), such combination may lead to increased serum levels of these agents and 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 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 may occur.

Other types of interaction

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 procedures compared to high-risk patients who received only intravenous fluid (hydration) prior to contrast procedures.

Special precautions for use.

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

Treatment with Lasix® requires regular medical supervision.

Particular 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),
hypoproteinaemia, e.g., 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 cerebrovascular disease or ischemic heart disease,
premature infants (risk of developing nephrocalcinosis/nephrolithiasis; monitoring of renal function and performing renal ultrasonography is required).

Symptomatic hypotension, leading to dizziness, syncope, 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 if free urinary drainage is ensured, since 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 Lasix® due to enhanced electrolyte excretion, serum electrolyte levels must be monitored regularly.

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

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

Existing conditions (such as hepatic cirrhosis, heart failure), concomitant use of medications (see section "Interaction with other medicinal products and other forms of interactions"), and diet may influence the development of electrolyte imbalances.

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

In nephrotic syndrome, careful dose selection is required 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 furosemide and risperidone (7.3%; mean age 89 years, age range 75–97 years) compared to groups receiving risperidone alone (3.1%; mean age 84 years, age range 70–96 years) or furosemide alone (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 outcomes.

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 should be carefully weighed before deciding to use this combination or concomitant therapy with other potent diuretics. In patients who received risperidone together with other diuretics, no increase in mortality was observed. Regardless of treatment, dehydration was a common risk factor for mortality; therefore, it should be avoided in the treatment of elderly patients with dementia (see section "Contraindications").

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

Use of Lasix® may lead to positive doping test results. Moreover, abuse of Lasix® as a doping agent may be hazardous to health.

Warnings regarding certain excipients.

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

Use during pregnancy or breastfeeding.

Pregnancy.

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

However, if furosemide must be administered 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 albumin binding sites 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 attributable to furosemide use have been reported in humans. However, there are insufficient data to draw definitive conclusions regarding potential 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 furosemide treatment.

Ability to influence the ability to drive and use machines.

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

Method of Administration and Dosage.

The dosage regimen is 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 should always be used. The medication should be taken on an empty stomach, swallowing the tablets whole with sufficient fluid (e.g., one glass of water).

Special Dosage Recommendations.

In acute renal failure, hypovolemia, arterial hypotension, and significant electrolyte or acid-base imbalances should be corrected before initiating furosemide therapy. Transition from intravenous to oral administration should be performed as soon as possible.

Edema due to chronic congestive heart failure / edema due to liver disease / edema due to chronic renal failure.

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

The usual daily maintenance dose corresponds to 1–2 tablets of Lasix® (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 administered as a single dose or divided into several doses.

Arterial hypertension. The usual dose corresponds to 1 tablet of Lasix® (equivalent to 40 mg of furosemide) once daily, used either as monotherapy or in combination with other medicinal products.

For children unable to take oral dosage forms, such as preterm infants and newborns, consideration should be given to using a parenteral formulation.

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 pharmaceutical form is indicated for children with body weight exceeding 10 kg.

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.

For children unable to take oral dosage forms, such as preterm infants and newborns, consideration should be given to using a parenteral formulation.

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 more 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 occur (symptoms: sweating, nausea, cyanosis, marked drop in blood pressure, impaired consciousness, or even coma).

Treatment

In case of overdose or development of signs of hypovolemia (arterial hypotension, orthostatic disturbances), Lasix® should be discontinued immediately.

If only a short time has passed after oral intake of furosemide, measures to eliminate initial poisoning 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 levels, and urinary excretion substances should be performed, with correction of any identified abnormalities as necessary.

In patients with urinary outflow disorders (e.g., due to prostate hyperplasia), free urine elimination must be ensured, as a sudden increase in urine production may lead to urinary retention with bladder overdistension.

Treatment of hypovolemia: fluid infusion.

Treatment of hypokalemia: potassium replacement therapy with potassium supplements.

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

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

ensure venous access;
in addition to standard emergency procedures, place the patient in a horizontal supine position with elevated lower limbs, ensure airway patency, and administer oxygen;
if necessary, implement other emergency intensive care measures (including administration of epinephrine, plasma expanders, 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. If 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 (especially in elderly patients), increased triglyceride levels.

Common: hyponatremia, hypochloremia (particularly in patients with restricted sodium chloride intake), hypokalemia (especially 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 may progress to overt diabetes (see section "Special Warnings and Precautions for Use").

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, paralysis), gastrointestinal signs (nausea, 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.

Rarely, tetany or development of cardiac arrhythmias due to hypomagnesemia has been observed.

Vascular system

Very common (when administered intravenously as appropriate dosage form): arterial hypotension, including orthostatic hypotension (see section "Special Warnings and Precautions for Use").

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 disturbances.

Renal and urinary system

Very common: increased blood creatinine levels.

Common: increased urine volume.

Rare: tubulointerstitial nephritis.

Frequency not known:

increased urinary sodium, increased urinary chloride, increased blood urea levels, symptoms of urinary dysfunction (e.g., in patients with benign prostatic hyperplasia, hydronephrosis, ureteral stenosis), up to urinary retention with development of secondary complications (see section "Special Warnings and Precautions for Use");
nephrocalcinosis and/or nephrolithiasis in premature infants (see section "Special Warnings and Precautions for Use");
renal failure (see section "Interaction with Other Medicinal Products and Other Forms of Interaction").

Gastrointestinal system

Uncommon: nausea.

Rare: vomiting, diarrhea.

Very rare: acute pancreatitis.

Hepatobiliary disorders

Very rare: intrahepatic cholestasis, increased transaminase levels.

Ear and labyrinth disorders

Uncommon: hearing disturbances, which are usually transient, particularly in patients with renal insufficiency, hypoproteinemia (e.g., in nephrotic syndrome), and/or with 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 flushing 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, 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 familial/genetic disorders

Frequency not known: increased risk of failure of closure of the arterial duct 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 a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions.

Keep out of the reach of children. Store in the original packaging at a temperature not exceeding +30 °C.

Packaging.

No. 45 (15 × 3): 15 tablets per strip, 3 strips per cardboard box.

Prescription status. Prescription only.

Manufacturer. Zentiva Private Limited, India.

Manufacturer's address.

Plot No. 3501 to 3515, 6301 to 6313 and 16.00 meter Road/c, G.I.D.C. Estate, AT&Post - Ankleshwar – 393 002, Dist. - Bharuch, India.

Marketing Authorization Holder. LLC "Sanofi-Aventis Ukraine", Ukraine / Sanofi-Aventis Ukraine LLC, Ukraine.