Furosemide bufus, 10 mg/ml 2 ml 10 pcs

Pharmacotherapeutic group:

Diuretic.

ATX code:

C03SA01

Pharmacological properties

Pharmacodynamics
Furosemide is a fast acting diuretic that is a sulfonamide derivative. Furosemide blocks the transport system of sodium, potassium, chlorine ions in the thick segment of the ascending knee of Genle loop, due to which its saluretic action depends on entering the drug into renal tubules lumen (due to mechanism of anion transport). Diuretic effect of Furosemide bufus is associated with inhibition of sodium chloride reabsorption in this part of the Genle loop. Secondary effects in relation to increased sodium excretion are: increased amount of excreted urine (due to osmotically bound water) and increased potassium secretion in the distal part of the renal tubule. At the same time, excretion of calcium and magnesium ions increases. When repeated administration of Furosemide bufus, its diuretic activity is not reduced, since the drug interrupts the tubulo-collicular feedback in Macula densa (a tubular structure closely related to the juxtaglomerular complex). Furosemide causes dose-dependent stimulation of the renin-angiotensin-aldosterone system.

In heart failure, furosemide rapidly reduces preload (through vein dilation), reduces pulmonary artery pressure and left ventricular filling pressure. This rapidly developing effect appears to be mediated through the effects of prostaglandins and therefore a condition for its development is the absence of disturbances in prostaglandin synthesis, in addition to which sufficient preservation of renal function is also required to realize this effect.

Furosemide has hypotensive effect due to increase in sodium excretion, decrease in circulating blood volume and decrease in response of vascular smooth muscle to vasoconstrictor effects (due to the natriuretic effect, furosemide reduces vascular response to catecholamines which concentration in patients with arterial hypertension is increased).

Dose-dependent increases in diuresis and natriuresis are observed with furosemide bufus at doses ranging from 10 mg to 100 mg (healthy volunteers). After intravenous administration of 20 mg of Furosemide bufus, the diuretic effect develops in 15 minutes and lasts about 3 hours.

The relationship between intrachannel concentrations of unbound (free) furosemide and its natriuretic effect is in the form of a sigmoidal curve with a minimum effective excretion rate of approximately Yumkg/min. Therefore, prolonged infusion of furosemide is more effective than repeated bolus administration. In addition, there is no significant increase in effect if the defined bolus dose is exceeded. When tubular secretion of furosemide is decreased or when the drug binds to albumin in the tubule lumen (e.g., in nephrotic syndrome), the effect of furosemide is reduced.

Pharmacokinetics
Time to reach maximum concentration after intravenous administration – 30 minutes. The volume of furosemide distribution is 0.1-0.2 l/kg body weight and varies significantly depending on the underlying disease. Furosemide binds to plasma proteins (more than 98%), mainly to albumin.

It is metabolized in the liver to form 4-chloro-5-sulfamoyl-anthranilic acid. Furosemide is excreted mostly unchanged and mainly by secretion in the proximal tubules. After intravenous furosemide administration, 60-70% of the administered dose is excreted by this route. Glucuronized metabolites of furosemide account for 10-20% of the drug excreted by the kidneys. The remaining dose is excreted through the intestine, apparently by biliary secretion. Final elimination half-life of furosemide after intravenous administration is approximately 1-1.5 hours. Bioavailability is 60-70%.

Furosemide penetrates the placental barrier and is excreted in the mother’s milk. Its concentrations in the fetus and the newborn are the same as in the mother.

Peculiarities of pharmacokinetics in certain groups of patients
In renal failure, excretion of furosemide is slower and the elimination half-life is longer; in severe renal failure, the final elimination half-life may be increased up to 24 hours.

In nephrotic syndrome, a decrease in plasma protein concentrations leads to increased concentrations of unbound furosemide (its free fraction) due to which the risk of ototoxic effects increases. On the other hand, the diuretic effect of furosemide in these patients may be reduced due to the binding of furosemide to albumin in the tubules and decreased tubular secretion of furosemide.

In hemodialysis and peritoneal dialysis and continuous ambulatory peritoneal dialysis, furosemide is slightly excreted.

In hepatic insufficiency, the half-life of furosemide is increased by 30-90%, mainly due to increased volume of distribution. Pharmacokinetic parameters in this category of patients may vary greatly.

In heart failure, severe, arterial hypertension and in elderly patients, furosemide excretion is delayed due to decreased renal function.

In premature and premature infants, excretion of furosemide may be delayed depending on the degree of maturity of the kidneys; metabolism of the drug in infants may also be delayed because their liver glucuronidation capacity is incomplete. In children whose age after conception is greater than 33 weeks, the final elimination half-life does not exceed 12 hours. In infants two months of age and older, the excretion of furosemide is not different from that of adults.

Indications

Active ingredient

Composition

Active ingredient:

Furosemide – 10.00 mg

Excipients:

Sodium chloride – 7.50 mg
sodium hydroxide – 1.28 mg
sodium hydroxide solution 1 M – to pH 8.0-9.3
water for injection – to 1 ml

How to take, the dosage

General recommendations
When prescribing the drug Furosemide bufus, it is recommended to use its lowest dose, sufficient to achieve the desired therapeutic effect. The dose is adjusted individually.

The drug Furosemide Boothus is given intravenously and, in exceptional cases, intramuscularly (when intravenous injection or ingestion is not possible). Intramuscular administration of the drug is not suitable for the treatment of acute conditions, such as pulmonary edema.

Injection of Furosemide bufus is carried out only when intravenous administration of the drug is not possible or when there is a violation of absorption of the drug in small intestine or when it is necessary to obtain the maximum rapid effect. When administering Furosemide bufus intravenously it is always recommended to switch to oral administration as soon as possible.

In case of intravenous administration, the drug should be administered slowly. The rate of intravenous administration should not exceed 4 mg/min. In patients with severe renal insufficiency (with serum creatinine concentration ≥ 5 mg/dL) it is recommended that the rate of intravenous administration of Furosemide bufus should not exceed 2.5 mg/min. To achieve optimal efficacy and suppression of counter-regulation (activation of renin-angiotensin and antinatriuretic neurohumoral regulatory links), prolonged intravenous infusion of Furosemide bufus is preferable to repeated intravenous bolus administration. If continuous intravenous infusion is not available after one or more bolus injections in acute conditions, low-dose infusion with short intervals between injections (approximately 4 hours) is preferable to intravenous bolus administration of higher doses with longer intervals between injections.

The parenteral solution has a pH of about 9 and has no buffering properties. If pH is lower than 7 the active substance may precipitate, therefore when diluting Furosemide bufus the pH of the obtained solution must be made to vary from neutral to slightly alkaline. For dilution can be used 0.9% sodium chloride solution. The diluted solution of Furosemide Bufus should be used, if possible, immediately after preparation.

The recommended maximum daily dose for intravenous administration in adults is 1500 mg and in children 20 mg.

The duration of treatment is determined by the physician individually depending on the indication.

Special recommendations for the dosage regimen in children
In children, the dose should be reduced according to body weight. The recommended dose for parenteral administration is 1 mg/kg/body weight per day, but not more than 20 mg/day.

Special recommendations for dosing regimen in adults
Edema syndrome in liver disease
Furosemide bufus is indicated in addition to treatment with aldosterone antagonists in case of their insufficient effectiveness. To prevent the development of complications, such as orthostatic circulatory dysregulation, water-electrolyte balance disorders or acid-base status, careful dose selection is required to ensure that fluid loss occurs gradually (at the beginning of treatment fluid loss up to about 0.5 kg of body weight per day is possible). If intravenous administration is necessary, the initial dose for intravenous administration is 20-40 mg.

Oedema syndrome in chronic renal failure
The natriuretic response to Furosemide bufus depends on several factors, including the severity of renal failure and blood sodium content, so the effect of the dose cannot be accurately predicted. In patients with chronic renal insufficiency, careful selection of the dose is required, by gradually increasing it so that fluid loss occurs gradually (at the beginning of treatment, fluid loss up to approximately 2 l/day may occur, which can be up to 280 mmol Na+ per day). In patients on hemodialysis, the maintenance dose is usually 250-1500 mg/day orally.

In intravenous administration, the dose of Furosemide bufus can be determined as follows: treatment begins with intravenous drip infusion at a rate of 0.1 mg/min and then gradually increases the infusion rate every 30 minutes depending on the therapeutic effect.

Acute renal failure (to maintain fluid excretion)
Before treatment with Furosemide bufus the patient should eliminate hypovolemia, arterial hypotension and significant disorders of water-electrolyte and acid-base status. It is recommended that the patient should be transferred as early as possible from intravenous Furosemide bufus to intake of Furosemide tablets (the dose of Furosemide tablets depends on the dose selected for intravenous administration).

The recommended initial intravenous dose is 40 mg. If the desired diuretic effect is not achieved after its administration, Furosemide bufus may be administered as a continuous intravenous infusion, starting at a rate of 50-100 mg/h.

Oedema in nephrotic syndrome
The recommended starting dose is 20-40 mg/day. The required dose is adjusted depending on the diuretic effect. The daily dose may be administered once or divided into several injections (see sections “Pharmacokinetics” and “Special indications”).

The edema syndrome in chronic heart failure
The recommended initial dose is 20-80 mg/day. The required dose is adjusted depending on the diuretic response. It is recommended that the daily dose be divided into 2-3 injections.

The edematous syndrome in acute heart failure
The recommended initial dose is 20-40 mg as an intravenous bolus injection. If necessary, the dose of Furosemide bufus may be adjusted depending on the therapeutic effect.

Hypertensive crisis
The recommended starting dose is 20-40 mg by intravenous bolus injection. The dose may be adjusted depending on the effect.

Maintenance of forced diuresis in poisoning
Furosemide is indicated in addition to intravenous infusion of electrolyte solutions. The recommended initial dose for intravenous administration is 20-40 mg. The dose depends on the response to furosemide. Before and during treatment with Furosemide bufus, fluid and electrolyte losses should be monitored and restored. In case of poisoning by substances with acidic or alkaline reaction, their excretion can be accelerated by additional alkalinization, or by increasing the acidity of the urine, respectively.

Interaction

Unrecommended combinations

Combinations in the use of which caution should be exercised

Interactions to be considered

Intravenously administered Furosemide Bufus is slightly alkaline, so it should not be mixed with medications with a pH less than 5.5.

Special Instructions

Before treatment with Furosemide Bufus, the presence of severe urinary outflow disorders, including unilateral ones, should be excluded.

Patients with partial urine outflow abnormalities should be closely monitored, especially at the start of treatment with Furosemide Bufus.

At the time of treatment, blood pressure, residual nitrogen, uric acid, and liver function should be monitored periodically.

Furosemide bufus treatment usually requires regular monitoring of serum sodium, potassium and creatinine concentration; especially careful monitoring should be conducted in patients with high risk of electrolyte and fluid balance disorders in cases of additional fluid and electrolyte losses (eg due to vomiting, diarrhea or heavy sweating) and if necessary appropriate treatment adjustments should be made.

Patients receiving high doses of furosemide should not be limited in their intake of table salt to avoid the development of hyponatremia and metabolic alkalosis.

When treating with Furosemide bufus it is always advisable to eat food rich in potassium (lean meat, potatoes, bananas, tomatoes, cauliflower, spinach, dried fruits, etc.). In some cases, taking potassium preparations or taking potassium-saving drugs may be indicated.

In patients with hypoproteinemia, e.g., associated with nephrotic syndrome, a careful change of the dose of Furosemide bufus is required (the effectiveness of furosemide may be impaired and its ototoxicity increased). If azotemia and oliguria appear or increase in patients with severe progressive renal disease, it is recommended to stop treatment.

In premature infants, regular monitoring of renal function and renal ultrasound examination are required (possibility of nephrolithiasis and nephrocalcinosis).

A higher incidence of death has been observed in elderly patients with dementia receiving risperidone and furosemide concomitantly compared to patients receiving risperidone alone or furosemide alone. The pathophysiological mechanism of this effect has not been established. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) has not been associated with increased mortality in elderly patients with dementia. In elderly patients with dementia, furosemide and risperidone should be administered simultaneously with caution, carefully weighing the benefit-risk ratio. Because dehydration is a common risk factor for increased mortality, patient dehydration should be avoided when deciding to use this combination in elderly patients with dementia.

The course or exacerbation of systemic lupus erythematosus may worsen.

The dosing regimen of patients with ascites due to liver cirrhosis should be determined in hospital (impaired water-electrolyte balance can lead to hepatic coma). Regular monitoring of plasma electrolyte content is indicated for this category of patients.

In patients with diabetes mellitus or with reduced glucose tolerance, periodic monitoring of blood and urine glucose levels is required.

In unconscious patients with adenoma of the prostate, ureteral narrowing, or hydronephrosis, monitoring of urine output is necessary due to the possibility of acute urinary retention.

Prompts for compatibility
Furosemide bufus should not be mixed with other medicinal products in the same syringe.

Emergency measures in the development of anaphylactic shock
The following measures are generally recommended:
At the first signs (sudden weakness, cold sweat, nausea, cyanosis) stop the injection, leaving the needle in the vein. Along with other normal emergency measures, the head and torso should be kept low and the airway kept clear.

Intravenous medications (dosage recommendations are for an adult of normal body weight; when treating children, the dosage should be reduced in proportion to body weight).

Injection of epinephrine (adrenaline) immediately intravenously: after diluting 1 ml of standard solution of adrenaline 1:1000 to 10 ml, first slowly inject 1 ml of the resulting solution (equal to 0.1 mg of adrenaline) under control of heart rate, blood pressure and heart rate. If necessary, the administration of epinephrine (adrenaline) may be continued by intravenous infusion. Simultaneously with the administration of epinephrine (adrenaline), intravenous administration of glucocorticosteroids (250-1000 mg of methylprednisolone or prednisolone), which can be repeated if necessary. In addition to these measures, intravenous infusion of plasma substitutes and/or electrolyte solutions is carried out to replenish the volume of circulating blood. If necessary: artificial respiration, oxygen inhalation, antihistamines.

Some side effects (e.g., significant decrease in BP) may impair the ability to concentrate and decrease the speed of psychomotor reactions, which may be dangerous while driving vehicles or performing other potentially dangerous activities. This especially refers to the period of starting treatment or increasing the drug dose, as well as to cases of concomitant use of hypotensive drugs. In such cases, it is not recommended to drive vehicles or engage in potentially dangerous activities.

Synopsis

Contraindications

Side effects

The following are the adverse reactions (HP) that have been identified in clinical trials as well as in the use of furosemide in clinical practice.

The following criteria were used to assess the incidence of HP: “very frequent” (≥1/10); “frequent” (≥1/100, < 1/10); “infrequent” (≥1/1000, < 1/100); “rare” (≥1/10000, < 1/1000); “very rare” (< 1/10000); “frequency unknown” (frequency cannot be determined from available data). HPs are grouped according to the system-organ classes of the MedDRA Medical Regulatory Dictionary, within each class HPs are listed in descending order of frequency of occurrence, within each group allocated by frequency of occurrence HPs are arranged in decreasing order of importance.

Disorders of the blood and lymphatic system
Frequent: hemoconcentration.
Infrequent: thrombocytopenia.
Rare: leukopenia, eosinophilia.
Very rare: agranulocytosis, aplastic anemia or hemolytic anemia.

Immune system disorders
Rare: severe anaphylactic or anaphylactoid reactions up to development of anaphylactic shock.
Frequency unknown: aggravation of the course or exacerbation of systemic lupus erythematosus.

Metabolic and nutritional disorders
Very common:

Often: hyponatremia, hypochloremia, hypokalemia, increased concentration of cholesterol in blood, increased concentration of uric acid in blood and development of gout attack.
Infrequently: decrease of glucose tolerance. Manifestation of latent diabetes mellitus is possible (see section “Indications”).
Frequency is unknown: hypocalcemia, hypomagnesemia, increased concentration of urea in blood, metabolic alkalosis, pseudosyndrome Bartter in improper and/or prolonged use of furosemide.

Nervous system disorders
Often: hepatic encephalopathy in patients with hepatocellular insufficiency (see section “Contraindications”).
Rarely: paresthesia.
Frequently unknown: dizziness, syncope (fainting) or loss of consciousness, headache.

Hearing and labyrinth disorders
Infrequent: hearing disorders, usually transient, especially in patients with renal failure, hypoproteinemia (e.g., in nephrotic syndrome) and/or too rapid intravenous administration of furosemide. Cases of deafness, sometimes irreversible, after oral or intravenous administration of furosemide have been reported.
Rarely: tinnitus.

Vascular disorders
Very common (for intravenous infusion): decreased blood pressure, including orthostatic hypotension.
Rare: vasculitis.
Frequency unknown: thrombosis.

Gastrointestinal disorders
Infrequent: nausea.
Rare: vomiting, diarrhea.
Very rare: acute pancreatitis.

Liver and biliary tract disorders
Very rare: cholestasis, increased liver transaminase activity.

Skin and subcutaneous tissue disorders
Infrequent: skin itching, urticaria, skin rash, bullous dermatitis, erythema multiforme, pemphigoid, exfoliative dermatitis, purpura, photosensitization reactions.
Frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, DRESS syndrome: drug rash with eosinophilia and systemic symptoms, lichenoid reactions.

Muscular, skeletal and connective tissue disorders
Frequency unknown: cases of rhabdomyolysis have been reported, often associated with severe hypokalemia (see Contraindications).

Renal and urinary tract disorders
Often: increased urine volume.
Rarely: tubulointerstitial nephritis.
Frequent unknown: increased sodium and chloride content in the urine, urinary retention (in patients with partial obstruction of the urinary tract, see section “Special Indications”), nephrocalcinosis/nephrolithiasis in preterm children (see section “Special Indications”), renal failure (see section “Interaction with other medicinal products”).

Congenital, familial and genetic disorders
Frequency unknown: Increased risk of arterial duct obstruction when furosemide is administered to premature infants during the first weeks of life.

General disorders and reactions at the site of administration
Rare: fever.
Frequency unknown: local reaction in the form of pain may occur after intramuscular injection.
Since some adverse reactions (such as changes in blood pattern, severe anaphylactic or anaphylactoid reactions, severe skin allergic reactions) under certain conditions can be life threatening for the patient, if any side effects occur, it is necessary to inform the doctor immediately.

The effect on the results of laboratory and instrumental studies
Frequency unknown: hyperglycemia, hypercholesterolemia, hyperuricemia, glucosuria, hypercalciuria.

Overdose

The clinical picture of acute or chronic overdose of the drug depends mainly on the degree and consequences of fluid and electrolyte loss. Overdose may manifest itself as hypovolemia, dehydration, hemoconcentration, cardiac rhythm and conduction disturbances (including atrioventricular blockade and ventricular fibrillation).

Symptoms: marked decrease in blood pressure (progressing up to the development of shock), collapse, acute renal failure with anuria, thrombosis, delirium, flaccid paralysis, apathy and confusion.

The treatment: correction of clinically significant disorders of water-electrolyte balance and acid-base state under control of serum electrolyte content, acid-base state parameters, hematocrit, as well as the prevention or therapy of possible severe complications arising from these disorders.

There is no specific antidote.

Pregnancy use