Cefuroxime-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Cefuroxime-Darnitsia (Cefuroxime-Darnitsa)

Composition:

Active substance: cefuroxime;

One vial contains sterile sodium cefuroxime salt equivalent to cefuroxime 0.75 g or 1.5 g.

Pharmaceutical form. Powder for solution for injection.

Main physico-chemical properties: white or almost white powder with a yellowish or cream-colored hue, slightly hygroscopic.

Pharmacotherapeutic group. Antibacterial agents for systemic use. Other β-lactam antibiotics. Second-generation cephalosporins. Cefuroxime.

ATC code J01D C02.

Pharmacological Properties

Pharmacodynamics

Cefuroxime is a second-generation cephalosporin antibiotic for parenteral administration. It exerts a bactericidal effect by inhibiting the synthesis of the microbial cell wall. It has a broad spectrum of activity. It is resistant to the action of most β-lactamases; therefore, it demonstrates activity against many ampicillin- or amoxicillin-resistant strains.

Highly active against:

• Gram-negative aerobes (Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus rettgeri, Providencia spp., Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae (including ampicillin-resistant strains), Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae (including penicillinase-producing strains), Neisseria meningitidis, Salmonella spp.);
• Gram-positive aerobes (Staphylococcus aureus, Staphylococcus epidermidis (including penicillinase-producing strains, but excluding methicillin-resistant strains), Streptococcus pyogenes (and other β-hemolytic streptococci), Streptococcus pneumoniae, Streptococcus group B (Streptococcus agalactiae), Streptococcus mitis (viridans group), Bordetella pertussis);
• Anaerobes;
• Gram-positive and gram-negative cocci (including Peptococcus and Peptostreptococcus species);
• Gram-positive bacteria (including most Clostridium spp.) and gram-negative bacteria (including Bacteroides spp. and Fusobacterium spp.), Propionibacterium spp.;
• Other microorganisms: Borrelia burgdorferi.

Microorganisms insensitive to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin-resistant strains of Staphylococcus aureus, methicillin-resistant strains of Staphylococcus epidermidis, Legionella spp.

Some microorganisms with strains insensitive to cefuroxime: Enterococcus (Streptococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp., Bacteroides fragilis.

Pharmacokinetics

After intramuscular administration of a 0.75 g dose, the time to reach peak serum concentration is approximately 30–45 minutes and is about 27 µg/mL. Following intravenous infusion of 0.75 g and 1.5 g, peak concentrations at the end of infusion are approximately 50 µg/mL and 100 µg/mL, respectively.

Plasma protein binding ranges from 33% to 50%. Therapeutic concentrations are achieved in pleural and synovial fluids, bile, sputum, bone tissue, cerebrospinal fluid (during meningitis), myocardium, skin, and soft tissues. Cefuroxime crosses the placenta, is excreted in breast milk, and penetrates the blood-brain barrier during meningitis.

Approximately 85–90% of the administered dose is excreted unchanged by the kidneys within 24 hours (50% via tubular secretion and 50% by glomerular filtration).

The elimination half-life after intravenous and intramuscular administration is approximately 70 minutes (in neonates, it may be 3 to 5 times longer).

Clinical characteristics.

Indications.

Treatment of infections caused by microorganisms sensitive to cefuroxime, or treatment of infections prior to identification of the causative agent of the infectious disease.

Respiratory tract infections: acute and chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess, postoperative infections of the thoracic organs;

infections of the throat and nose: sinusitis, tonsillitis, pharyngitis;

urinary tract infections: acute and chronic pyelonephritis, cystitis, asymptomatic bacteriuria;

soft tissue infections: cellulitis, erysipelas, wound infections;

bone and joint infections: osteomyelitis, septic arthritis;

infections in obstetrics and gynecology: pelvic inflammatory diseases;

gonorrhea, especially when penicillin is contraindicated;

other infections, including septicemia and meningitis.

Prophylaxis of infectious complications following surgery on the chest and abdominal cavity, pelvic organs, as well as vascular, cardiovascular, and orthopedic surgeries.

In most cases, monotherapy with cefuroxime is effective; however, if necessary, the drug may be used in combination with aminoglycoside antibiotics or metronidazole (orally, as suppositories, or by injection).

In cases of existing or suspected mixed aerobic and anaerobic infections (e.g., peritonitis, aspiration pneumonia, lung abscess, pelvic or brain abscess) or high likelihood of such infections (e.g., during surgery on the large intestine or in gynecological surgery), the use of cefuroxime in combination with metronidazole is appropriate.

For the treatment of pneumonia and acute exacerbations of chronic bronchitis, the drug may be administered parenterally prior to oral administration of cefuroxime axetil, when necessary.

Contraindications.

Hypersensitivity to cefuroxime or to any other component of the drug.

Hypersensitivity to cephalosporin antibiotics.

History of severe hypersensitivity (anaphylactic reactions) to other β-lactam antibiotics (penicillins, monobactams, and carbapenems).

Interaction with other medicinal products and other forms of interaction.

Medicinal products that reduce platelet aggregation (nonsteroidal anti-inflammatory drugs, salicylates, sulfinpyrazone) – cefuroxime, by inhibiting intestinal flora, interferes with vitamin K synthesis, thereby increasing the risk of bleeding.

Anticoagulants – enhanced anticoagulant effect, resulting in an increased risk of bleeding. Concomitant use with oral anticoagulants may lead to an increased international normalized ratio (INR).

Diuretics and potentially nephrotoxic antibiotics (e.g., aminoglycosides) – increased risk of nephrotoxic effects. Cephalosporin antibiotics in high doses should be administered with caution in patients receiving treatment with potent diuretics (such as furosemide) or potentially nephrotoxic agents (such as aminoglycoside antibiotics), as renal function impairment cannot be excluded with such drug combinations. When used in combination with aminoglycoside antibiotics, an additive effect is observed, and in some cases, synergy may occur.

Probenecid. Cefuroxime is eliminated via glomerular filtration and tubular secretion. Concomitant administration of probenecid is not recommended, as it reduces tubular secretion and decreases renal clearance of cefuroxime, leading to increased serum concentrations of cefuroxime.

Oral contraceptives – cefuroxime suppresses intestinal microflora, thereby reducing enterohepatic reabsorption of estrogens, which may result in decreased efficacy of combined oral contraceptives.

Interference with diagnostic tests.

During treatment with cefuroxime, blood and plasma glucose levels should be measured using glucose oxidase or hexokinase methods, as false-negative results may occur with the ferricyanide test (see section "Special precautions").

Cefuroxime does not affect the results of enzymatic methods for detecting glucosuria.

Cefuroxime may slightly affect methods based on copper reduction (Benedict’s, Fehling’s, Clinitest), but this does not lead to pseudopositive results, unlike with some other cephalosporins.

Cefuroxime does not interfere with creatinine measurements using alkaline picrate.

Development of a positive Coombs test during cefuroxime therapy may affect blood group determination due to the ability of cephalosporins to adsorb onto the surface of red blood cell membranes and interact with antibodies (see section « Adverse reactions*»* ).

Special precautions for use.

Use with caution in newborns, premature infants, patients with severe renal function impairment, colitis, impaired blood coagulation, peptic ulcer of the stomach and duodenum, elderly patients, and patients with renal insufficiency.

Hypersensitivity reactions.

As with other β-lactam antibiotics, severe and sometimes fatal hypersensitivity reactions have been reported. Hypersensitivity reactions progressing to Kounis syndrome—acute allergic coronary artery spasm that may lead to myocardial infarction—have been reported (see section "Adverse reactions"). In the event of severe hypersensitivity reactions, cefuroxime therapy should be immediately discontinued and appropriate emergency measures initiated.

Prior to initiating therapy, assess the patient’s history for severe hypersensitivity reactions to cefuroxime, cephalosporin antibiotics, or other β-lactam antibiotics. The drug should be administered with caution in patients with a history of hypersensitivity reactions to other β-lactam antibiotics.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS syndrome, which may be life-threatening or fatal, have been reported with cefuroxime therapy (see section "Adverse reactions").

Patients should be informed of the signs and symptoms of these reactions and carefully monitored for skin reactions during drug administration. If signs or symptoms suggestive of these reactions occur, cefuroxime should be immediately discontinued and alternative therapy considered. If a serious reaction such as SJS, TEN, or DRESS syndrome develops during cefuroxime therapy, re-administration of cefuroxime to this patient is absolutely contraindicated.

Concomitant therapy with potent diuretics or aminoglycosides.

With prolonged use, renal function should be monitored in elderly patients and in patients with known pre-existing renal impairment (especially when high doses are used), and prophylaxis against dysbiosis should be implemented. Cephalosporin antibiotics in high doses should be used cautiously in patients receiving concomitant therapy with potent diuretics such as furosemide or aminoglycoside antibiotics, as there have been reports of adverse effects on renal function with such combinations. In patients with impaired renal function, the dose should be reduced according to the severity of renal insufficiency and the susceptibility of the causative organism. Renal function must be monitored in these patients, as well as in elderly patients and those with pre-existing renal insufficiency (see section "Dosage and administration").

Growth of resistant microorganisms.

As with other antibiotics, prolonged use of cefuroxime may lead to overgrowth of resistant microorganisms (e.g., Candida, Enterococci, Clostridium difficile), which may necessitate discontinuation of therapy (see section "Adverse reactions").

Cases of pseudomembranous colitis of varying severity—from mild to life-threatening—have been reported with antibiotic use. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic therapy (see section "Adverse reactions"). In cases of persistent or severe diarrhea, or if abdominal cramps occur, therapy should be immediately discontinued, further patient evaluation conducted, and specific treatment against Clostridium difficile considered. Medicinal products that inhibit peristalsis should not be prescribed.

Intra-abdominal infections.

Due to its spectrum of activity, cefuroxime is not suitable for the treatment of infections caused by non-fermenting Gram-negative bacteria.

Intracameral administration and ocular disorders.

Cefuroxime is not intended for intracameral administration. Individual cases of serious ocular adverse reactions have been reported following inappropriate intracameral use of sodium cefuroxime approved for intravenous/intramuscular administration. These reactions included macular edema, retinal edema, retinal detachment, retinal toxicity, visual disturbances, decreased visual acuity, blurred vision, corneal opacity, and corneal edema.

Other important information.

After resolution of disease symptoms, treatment should be continued for an additional 48–72 hours.

As with other meningitis treatment regimens, cases of moderate to severe hearing loss have been reported in several children treated with cefuroxime.

As with treatment using other antibiotics, cultures of Haemophilus influenzae have been detected in cerebrospinal fluid 18–36 hours after cefuroxime injection. However, the clinical significance of this phenomenon is unknown.

When using cefuroxime in a sequential therapy regimen, the timing of transition to oral cefuroxime depends on the severity of infection, the patient’s clinical condition, and microbial susceptibility. Transition to oral administration is permitted upon clinical improvement. If no clinical improvement occurs within 72 hours, parenteral administration should be continued. Prior to using the oral formulation, the product’s instructions for medical use should be consulted.

Alcohol consumption is contraindicated during treatment, as disulfiram-like effects may occur (facial flushing, abdominal and epigastric cramps, nausea, vomiting, headache, hypotension, tachycardia, and respiratory difficulty).

Important information on excipients.

Each 0.75 g vial of cefuroxime contains 42 mg (1.8 mEq) of sodium.

Each 1.5 g vial of cefuxime contains 84 mg (3.6 mEq) of sodium.

This should be taken into account for patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

Pregnancy.

Data on the use of cefuroxime in pregnant women are limited. Reproductive toxicity has not been observed in animal studies. Cefuroxime-Darnytsia should be administered to pregnant women only when the potential benefit justifies the potential risk.

Cefuroxime crosses the placenta and reaches therapeutic levels in amniotic fluid and umbilical cord blood after intramuscular or intravenous dosing in the mother.

Breastfeeding.

Cefuroxime is excreted in breast milk in small amounts. With therapeutic doses, adverse reactions in the infant are not expected, but the risk of diarrhea or fungal mucosal infections in the infant cannot be excluded. Therefore, a decision should be made whether to discontinue breastfeeding or to discontinue/abstain from cefuroxime therapy, taking into account the benefits of breastfeeding for the infant and the benefits of therapy for the mother.

Fertility.

There are no data on the effect of sodium cefuroxime on human fertility. Studies on reproductive function in animals have not shown any effect of this drug on fertility.

Ability to affect reaction speed when driving or operating machinery.

No studies have been conducted on the effect of cefuroxime on the ability to drive vehicles or operate machinery. However, considering the known adverse reactions, it can be concluded that cefuroxime is unlikely to affect reaction speed when driving or operating machinery.

Method of Administration and Dosage.

Sensitivity to cefuroxime varies among different regions and may change over time. Local antibiotic susceptibility data should be consulted when necessary.

The medicinal product should be administered only intramuscularly or intravenously.

Since cefuroxime is also available in an oral formulation, a sequential switch from parenteral to oral therapy may be performed when clinically appropriate.

Solvents for cefuroxime powder: 5% glucose injection solution, 10% glucose injection solution, 0.9% sodium chloride injection solution, 5% glucose solution with 0.9%, 0.45%, or 0.225% sodium chloride injection solution, Ringer's solution, Ringer-lactate solution, Hartmann's solution, water for injections.

Intramuscular administration: Add 3 mL of water for injections to 0.75 g of the medicinal product and gently shake the vial until a homogeneous suspension is formed.

Intravenous administration: Dissolve 0.75 g of the medicinal product in not less than 6 mL of water for injections, or 1.5 g in 15 mL of solvent in a 20 mL syringe; gently shake until complete dissolution.

For short-term intravenous infusions (up to 30 minutes): Dissolve 0.75 g of the medicinal product in not less than 25 mL of solvent (water for injections, 0.9% sodium chloride solution, 5% glucose solution), or 1.5 g in 50–100 mL of solvent.

Solvents for intravenous administration: 5% glucose injection solution, 5% glucose and lactated Ringer's injection solution, 5% glucose and 0.9% sodium chloride injection solution, 10% glucose injection solution, lactated Ringer's injection solution, 0.9% sodium chloride injection solution. The resulting solutions may be administered directly into the vein or into the infusion tubing during infusion therapy. Color intensity changes may occur during storage of prepared solutions.

Adults: Administer 0.75 g of the medicinal product intramuscularly or intravenously three times daily. In more severe infections, administer 1.5 g intravenously three times daily. If necessary, the dosing interval may be reduced to 6 hours. The daily dose of the medicinal product is 3–6 g. When required, certain infections may be treated as follows: 750 mg or 1.5 g twice daily (intravenously or intramuscularly), followed by oral cefuroxime.

Infants and children: Administer at a dose of 30–100 mg/kg/day in 3–4 divided doses. For most infections, the optimal daily dose is 60 mg/kg/day.

Neonates: Administer 30–100 mg/kg/day in 2–3 divided doses. It should be noted that the elimination half-life of cefuroxime during the first weeks of life may be 3–5 times longer than in adults.

In gonorrhea: Administer a single dose of 1.5 g as one or two injections of 0.75 g each, administered into both buttocks.

In meningitis: May be used as monotherapy in bacterial meningitis caused by susceptible strains. Adults: Administer 3 g intravenously every 8 hours. Infants and children: Administer 200–240 mg/kg/day intravenously in 3–4 divided doses. This dosage may be reduced to 100 mg/kg/day intravenously after 3 days of treatment or upon clinical improvement. Neonates: Administer 100 mg/kg/day intravenously. The dose may be reduced to 50 mg/kg/day upon clinical improvement.

Prophylaxis.

For prevention of infections during abdominal, pelvic, and orthopedic surgeries: Administer 1.5 g intravenously as a single dose during anesthesia. If necessary, additional doses of 0.75 g intramuscularly may be given three times daily for the following 24–48 hours.

For cardiac, pulmonary, esophageal, and vascular surgeries: The usual dose is 1.5 g intravenously administered at the induction of anesthesia, followed by supplementary intramuscular doses of 0.75 g three times daily for the next 24–48 hours.

In joint replacement surgery: Mix 1.5 g of the medicinal product with one packet of methylmethacrylate polymer cement before adding the liquid monomer.

Sequential therapy.

Pneumonia: Administer 1.5 g of the medicinal product 2–3 times daily (intramuscularly or intravenously) for 48–72 hours, followed by transition to oral cefuroxime 500 mg twice daily for 7–10 days.

Exacerbation of chronic bronchitis: Administer 0.75 g of the medicinal product 2–3 times daily (intramuscularly or intravenously) for 48–72 hours, followed by transition to oral cefuroxime 500 mg twice daily for 7 days.

The duration of both parenteral and oral therapy should be determined based on the severity of infection and the patient's clinical condition.

Renal impairment.

Cefuroxime is eliminated via the kidneys. Therefore, as with other similar antibiotics, dosage reduction is recommended in patients with impaired renal function to compensate for slower drug excretion. Standard dosing (750 mg–1.5 g three times daily) does not need to be reduced if creatinine clearance is greater than 20 mL/min. For adults with moderate renal impairment (creatinine clearance 10–20 mL/min), the recommended dose is 750 mg twice daily. In more severe cases (creatinine clearance less than 10 mL/min), the dose is 750 mg once daily.

During hemodialysis, administer 750 mg intravenously or intramuscularly at the end of each dialysis session. In addition to parenteral administration, cefuroxime may be added to peritoneal dialysis fluid (usually 250 mg per 2 liters of dialysis fluid). For patients undergoing scheduled hemodialysis or high-flux hemofiltration in intensive care units, the recommended dose is 750 mg twice daily. Patients undergoing low-flux hemofiltration should follow the dosing regimen recommended for renal impairment.

Children.

May be administered from the first days of life. The safety profile of cefuroxime in children corresponds to that observed in adults.

Overdose.

Overdose of cephalosporins may lead to symptoms of central nervous system irritation, potentially resulting in seizures, encephalopathy, and coma.

Overdose symptoms may occur if the dose is not appropriately reduced in patients with renal impairment (see sections "Method of Administration and Dosage" and "Special Instructions").

Treatment: Administration of anticonvulsants, airway protection, ventilation and perfusion support, monitoring and maintenance of vital signs, blood gases and electrolytes at required levels, hemodialysis and peritoneal dialysis.

Adverse Reactions

The most commonly observed adverse reactions are neutropenia, eosinophilia, and transient elevations in liver enzymes or bilirubin levels, particularly in patients with pre-existing liver disease. However, there are no data indicating hepatotoxic effects or injection site reactions.

The frequency of adverse reactions listed below is approximate, as sufficient data for precise calculation are lacking for most reactions. Moreover, the incidence of adverse reactions associated with cefuroxime varies depending on the indication.

The classification of adverse effects from very common to rare is based on clinical trial data. Most adverse reactions are rare (less than 1/10,000), generally mild and reversible, and are primarily derived from post-marketing surveillance data, reflecting reporting rates rather than true incidence. Additionally, the frequency of adverse reactions varies by indication and is presented below by system organ class, frequency, and severity according to the MedDRA classification.

Criteria for assessing frequency of adverse effects: very common (≥ 1/10); common (≥ 1/100 and < 1/10); uncommon (≥ 1/1,000 and < 1/100); rare (≥ 1/10,000 and < 1/1,000); very rare (< 1/10,000); and frequency not known (cannot be estimated from available data).

Ear and labyrinth disorders: very rare – hearing loss of mild to moderate severity has been observed in children treated for meningitis.

Gastrointestinal disorders: uncommon – gastrointestinal discomfort, abdominal pain, nausea, vomiting, diarrhea; frequency not known – cases of pseudomembranous colitis have been reported (see section "Special precautions").

Hepatobiliary disorders: common – transient increase in liver enzyme activity (mainly in patients with pre-existing liver pathology, but no data on hepatotoxic effects); uncommon – transient increase in bilirubin levels, cholestasis. Transient elevations in serum liver enzymes or bilirubin were reversible.

Renal and urinary disorders: frequency not known – increased serum creatinine and blood urea nitrogen levels, decreased creatinine clearance.

Nervous system disorders: rare – headache, dizziness, seizures.

Cardiac disorders: frequency not known – Kounis syndrome.

Blood and lymphatic system disorders: common – eosinophilia, neutropenia, decreased hematocrit, decreased hemoglobin; uncommon – leukopenia, positive Coombs test; frequency not known – thrombocytopenia, anemia, hemolytic anemia. Cephalosporins may adsorb onto the surface of red blood cell membranes and interact with antibodies, leading to a positive Coombs test, which may interfere with blood grouping and hemolytic anemia diagnosis.

Immune system disorders: uncommon – hypersensitivity reactions, including skin rash, maculopapular rash, pruritus, urticaria; frequency not known – drug rash with eosinophilia and systemic symptoms (DRESS syndrome), interstitial nephritis, cutaneous vasculitis, anaphylaxis, angioedema, anaphylactic shock.

Skin and subcutaneous tissue disorders: frequency not known – polymorphic erythema, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug-induced eosinophilia with systemic symptoms (DRESS syndrome).

Administration site reactions: common – reactions at the injection site, which may include pain; with intravenous administration – burning sensation at the injection site, thrombophlebitis. The likelihood of pain following intramuscular injection increases with higher doses, but this is unlikely to lead to discontinuation of treatment.

Infections and infestations: frequency not known – prolonged use may lead to overgrowth of non-susceptible microorganisms, such as Candida, Enterococci, Clostridium difficile.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.

Shelf life. 2 years.

Storage conditions.

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

Incompatibilities.

Cefuroxime should not be mixed in the same syringe with aminoglycoside antibiotics.

The pH of a 2.74% sodium bicarbonate injection solution significantly affects the color of the solution; therefore, this solution is not recommended for diluting the medicinal product. However, if necessary and the patient is receiving a sodium bicarbonate infusion intravenously, cefuroxime may be administered directly into the infusion line.

1.5 g of cefuroxime dissolved in 15 mL of water for injections may be used concomitantly with metronidazole injection (500 mg/100 mL); both medicinal products retain their activity for 24 hours at temperatures below 25 °C.

1.5 g of cefuroxime is compatible with 1 g of azlocillin (in 15 mL of diluent) or with 5 g (in 50 mL of diluent) for 24 hours at 4 °C and for 6 hours at temperatures up to 25 °C.

Cefuroxime (5 mg/mL) may be stored for 24 hours at 25 °C in 5% or 10% xylitol injection solution.

The medicinal product is compatible with solutions containing up to 1% lidocaine hydrochloride.

Cefuroxime is compatible with most commonly used intravenous infusion solutions. It remains stable for 24 hours at room temperature in the following solutions: 0.9% sodium chloride injection; 5% glucose injection; 0.18% sodium chloride with 4% glucose injection; 5% glucose with 0.9% sodium chloride injection; 5% glucose with 0.45% sodium chloride injection; 5% glucose with 0.225% sodium chloride injection; 10% glucose injection; 10% invert sugar in water for injection; Ringer’s solution; Ringer’s lactate solution; M/6 sodium lactate solution; Hartmann’s solution.

The stability of the medicinal product in 0.9% sodium chloride injection with 5% glucose is not altered in the presence of hydrocortisone sodium phosphate.

The medicinal product is also compatible for 24 hours at room temperature when diluted in infusion solutions:

• with heparin (10 or 50 units/mL) in 0.9% sodium chloride injection;
• with potassium chloride solution (10 or 40 mEq/L) in 0.9% sodium chloride injection.

Packaging.

1 vial per carton; 5 vials in a blister pack; 1 blister pack per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and location of business activity.

13, Boryspilska Street, Kyiv, 02093, Ukraine.