Cefotaxime-bhfz

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFOTAXIME-BHFS (CEFOTAXIME-BCPP)

Composition:

Active substance: cefotaxime;

Each vial contains cefotaxime (as sterile cefotaxime sodium salt) 500 mg or 1000 mg.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical characteristics: white or slightly yellowish hygroscopic powder.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Beta-lactam antibiotics. Third-generation cephalosporins. ATC code J01DD01.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Cefotaxime is a broad-spectrum parenteral antibiotic of the third-generation cephalosporins. Cefotaxime inhibits enzymes responsible for bacterial cell wall synthesis. This leads to bacterial cell lysis.

Resistance mechanisms

Bacterial resistance to cefotaxime may result from one or more of the following mechanisms:

• Hydrolysis by beta-lactamase. Cefotaxime may be hydrolyzed by many so-called broad-spectrum beta-lactamases. It is also hydrolyzed by chromosomally encoded (AmpC-type) beta-lactamases.
• Resistance based on impermeability.
• Expression of efflux pumps.

Several of these mechanisms may act simultaneously within a single bacterium.

Bacteria resistant to cefotaxime may exhibit varying degrees of cross-resistance to other beta-lactam antibiotics. Gram-negative bacteria resistant to cefotaxime show cross-resistance to other broad-spectrum third-generation cephalosporins (ceftazidime, ceftriaxone).

Clinical breakpoints

The clinical breakpoints of minimum inhibitory concentration (MIC) for cefotaxime, which distinguish susceptible microorganisms from resistant ones, as recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), are presented in the table below.

Clinical breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for cefotaxime:

Pathogenic microorganism	Susceptible	Resistant
Enterobacteriaceae	≤ 1 mg/l	> 2 mg/l
S. pneumoniae	≤ 0.5 mg/l	> 2 mg/l
Other Streptococci	≤ 0.5 mg/l	> 0.5 mg/l
H. influenzae	≤ 0.12 mg/l	> 0.12 mg/l
M. catarrhalis	≤ 1 mg/l	> 2 mg/l
N. gonorrhoeae	≤ 0.12 mg/l	> 0.12 mg/l
N. meningitidis	≤ 0.12 mg/l	> 0.12 mg/l
Intermediate values not species-related	≤ 1 mg/l	> 2 mg/l
Susceptibility of staphylococci (Staphylococcus) to cephalosporins is inferred from their susceptibility to methicillin. Susceptibility of streptococci (Streptococcus) of groups A, B, C, G is inferred from their susceptibility to benzylpenicillin.

Antibacterial spectrum of activity

The prevalence of resistance among individual species may vary depending on the region and time. When treating serious infections, it is advisable to take into account local information on resistance. If necessary, consultation with specialists should be sought when local resistance prevalence has reached a level at which the benefit of use is questionable.

Usually susceptible microorganisms

Aerobic Gram-positive bacteria Methicillin-susceptible Staphylococcus aureus Methicillin-susceptible coagulase-negative staphylococci Methicillin-susceptible Staphylococcus epidermidis Methicillin-susceptible Staphylococcus haemolyticus Group A streptococci (including Streptococcus pyogenes) Group B streptococci Streptococcus pneumoniae Streptococcus viridans group Aerobic Gram-negative bacteria Citrobacter spp. (except Citrobacter freundii) Escherichia coli Haemophilus influenzae Moraxella catarrhalis Neisseria gonorrhoeae Neisseria meningitidis Klebsiella spp. Proteus mirabilis Serratia spp. Yersinia enterocolitica Other microorganisms Borrelia spp.

Microorganisms that may develop resistance

Bacteroides fragilis Enterobacter spp. Aerobic Gram-positive bacteria Methicillin-resistant Staphylococcus aureus Methicillin-resistant coagulase-negative staphylococci Aerobic Gram-negative bacteria Acinetobacter spp. Citrobacter freundii Morganella morganii Providencia spp. Pseudomonas aeruginosa Stenotrophomonas maltophilia

Inherently resistant microorganisms

Aerobic Gram-positive bacteria Enterococcus spp. Other microorganisms Chlamydia spp. Legionella pneumophila Listeria spp. Mycoplasma spp. Treponema pallidum

Pharmacokinetics

Cefotaxime is administered parenterally. After a single intravenous dose of cefotaxime 1 g, its serum concentration was approximately 81–102 mg/L at 5 minutes and 46 mg/L at 15 minutes. After a single intravenous dose of cefotaxime 2 g, serum concentration was 167–214 mg/L at 8 minutes.

After intramuscular administration of cefotaxime, maximum serum concentration (approximately 20 mg/L following a 1 g dose) was achieved within 30 minutes.

Distribution

Cefotaxime rapidly penetrates tissues, crosses the placental barrier, and reaches high concentrations in fetal tissues (up to 6 mg/kg). It appears in breast milk only in low amounts (milk concentration of 0.4 mg/L after a 2 g dose).

In cases of inflammation of the meninges, cefotaxime and desacetylcefotaxime penetrate into the cerebrospinal fluid (CSF) and achieve therapeutically effective concentrations (e.g., in infections caused by Gram-negative bacteria and pneumococci).

The apparent volume of distribution is 21–37 L. Plasma protein binding is approximately 25–40%.

Metabolism

Cefotaxime undergoes extensive metabolism in the human body. Approximately 15–25% of the parenterally administered dose is excreted as O-desacetylcefotaxime. This metabolite possesses antibacterial activity.

In addition to desacetylcefotaxime, two other inactive metabolites (lactones) are formed. The lactone is formed from desacetylcefotaxime as a short-lived intermediate, which is rapidly no longer detectable in urine or plasma, as it quickly converts into stereoisomers of the lactone with an open ring structure (β-lactam ring). These are also excreted in urine.

Excretion

Excretion of cefotaxime and desacetylcefotaxime occurs predominantly via the renal route. A small percentage (about 2%) is excreted in bile. In urine collected over 6 hours, 40–60% of the dose was recovered unchanged and approximately 20% as desacetylcefotaxime. After intravenous administration of radiolabeled cefotaxime, more than 80% was excreted in urine, of which 50–60% was unchanged and the remainder as three metabolites.

Total clearance of cefotaxime is 240–390 mL/min, and renal clearance is 130–150 mL/min.

The elimination half-life of cefotaxime and its active metabolite in serum is 50–80 minutes and 125 minutes, respectively. In elderly patients (>80 years of age), the elimination half-life for cefotaxime and the active metabolite is 120–150 minutes and 5 hours, respectively.

In cases of severe renal impairment (creatinine clearance 3–10 mL/min), the elimination half-life of cefotaxime may be prolonged to 2.5–10 hours.

Under these conditions, cefotaxime accumulates only to a minor extent, in contrast to active and inactive metabolites.

Both cefotaxime and desacetylcefotaxime are significantly removed from the blood by hemodialysis.

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to the drug:

• infections of ENT organs (tonsillitis, otitis);
• respiratory tract infections (bronchitis, pneumonia, pleurisy, abscesses);
• complicated infections of the genitourinary system;
• septicemia, bacteremia (if the infection is caused by gram-negative bacteria, it should be combined with another appropriate antibiotic);
• intra-abdominal infections (including peritonitis): when treating intra-abdominal infections, cefotaxime should be used in combination with an antibiotic active against anaerobic microorganisms;
• severe skin and soft tissue infections;
• bone and joint infections;
• meningitis (except listeriosis) and other central nervous system infections;
• prophylaxis of infections after gastrointestinal, urological, and obstetrical-gynecological surgeries.

Contraindications.

Hypersensitivity to cephalosporin antibiotics and other beta-lactam antibiotics, hypersensitivity to lidocaine (for intramuscular administration); bleeding, enterocolitis in medical history (especially ulcerative nonspecific colitis).

Atrioventricular blocks without an implanted cardiac pacemaker, severe heart failure.

Interaction with other medicinal products and other types of interactions.

When cefotaxime is used concomitantly with nephrotoxic drugs (aminoglycosides) and potent diuretics (ethacrynic acid, furosemide), colistin, polymyxin, the risk of developing renal failure increases. In such patients, kidney function should be monitored.

An antagonistic effect is possible with bacteriostatic antibiotics (e.g., tetracyclines, erythromycin, chloramphenicol).

Should not be mixed with solutions of aminoglycosides – they must be administered separately.

With nifedipine, the bioavailability of cefotaxime increases by 70%.

With probenecid, tubular secretion of cefotaxime is blocked, and its elimination half-life is prolonged. This approximately doubles cefotaxime exposure and reduces renal clearance by about 50% at therapeutic doses. Due to the wide therapeutic range of cefotaxime, dosage adjustment is not required in patients with normal renal function. However, dosage adjustment may be necessary in patients with impaired renal function.

Cefotaxime must not be used together with lidocaine:

• for intravenous administration;
• in children under 30 months of age;
• in patients with a history of hypersensitivity to lidocaine;
• in patients with heart block.

During treatment with cefotaxime, the effectiveness of oral contraceptives may be reduced; therefore, additional contraceptive measures should be used during this period.

Special precautions.

As with other broad-spectrum antibiotics, prolonged use of cefotaxime may lead to overgrowth of resistant microorganisms, necessitating discontinuation of treatment. If superinfection occurs during therapy, appropriate antimicrobial therapy should be initiated.

The drug should be administered with caution in patients with impaired renal or hepatic function. In patients with renal impairment, the dose should be reduced according to the severity of renal dysfunction and pathogen susceptibility.

Anaphylactic reactions

Serious, including fatal, hypersensitivity reactions have been reported in patients receiving cefotaxime. If a hypersensitivity reaction occurs, treatment should be discontinued immediately. Cefotaxime is strictly contraindicated in patients with a history of immediate-type hypersensitivity reactions to cephalosporins.

Since cross-allergy between penicillins and cephalosporins occurs in 5–10% of cases, cephalosporins should be used with particular caution in individuals with hypersensitivity to penicillins.

Cefotaxime should be prescribed cautiously in patients with allergic diathesis or asthma.

Severe skin reactions

During the post-marketing period, cases of severe skin adverse reactions associated with cefotaxime therapy have been reported, including acute generalized exanthematous pustulosis (AGEP), Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be life-threatening or fatal.

Patients should be informed about the signs and symptoms of skin reactions when cefotaxime is prescribed. If symptoms suggestive of these reactions occur, cefotaxime should be discontinued immediately. If AGEP, SJS, TEN, or DRESS syndrome develops during cefotaxime therapy, the drug must not be restarted and must be permanently discontinued.

In children, rash may be mistaken for the underlying infection or another infectious process; therefore, physicians should consider the possibility of a reaction to cefotaxime in children who develop rash and fever during therapy.

Clostridium difficile-associated disease (e.g., pseudomembranous colitis)

Diarrhea, particularly severe and/or persistent, occurring during or within weeks after treatment may be caused by Clostridium difficile (CDAD). CDAD may range in severity from mild to life-threatening, with the most severe form being pseudomembranous colitis. Diagnosis of this rare but potentially fatal condition can be confirmed by colonoscopy and/or histological examination. This diagnosis should be considered in patients who develop diarrhea during or after cefotaxime administration. If pseudomembranous colitis is suspected, cefotaxime should be discontinued immediately and appropriate specific antibiotic therapy should be initiated promptly. Clostridium difficile-associated disease may lead to fecal stasis. Medicinal products that inhibit intestinal peristalsis should not be used.

Hematological reactions

Leukopenia, neutropenia, and, less frequently, bone marrow suppression, pancytopenia, and agranulocytosis may occur during cefotaxime therapy, especially with prolonged treatment. If treatment lasts longer than 7–10 days, blood counts should be monitored regularly. If blood test results (hemogram) deviate from normal, treatment should be discontinued.

There have been reports of several cases of eosinophilia and thrombocytopenia, which resolved rapidly after discontinuation of therapy. Cases of hemolytic anemia have also been reported.

Patients with renal impairment

Dosage must be adjusted based on calculated creatinine clearance. Caution should be exercised when cefotaxime is used concomitantly with aminoglycosides, furosemide, probenecid, or other nephrotoxic medicinal products. Renal function should be monitored regularly in elderly patients and in patients with pre-existing renal impairment.

Neurotoxicity (encephalopathy)

High doses of beta-lactam antibiotics, including cefotaxime, especially in patients with renal impairment, may lead to encephalopathy (e.g., impaired consciousness, abnormal movements, and seizures).

If such reactions occur, patients should seek immediate medical attention before continuing treatment.

During post-marketing surveillance, potentially life-threatening arrhythmias have been reported in a very small number of patients receiving cefotaxime via rapid intravenous administration through a central venous catheter. Therefore, the recommended infusion time should be strictly observed.

Effect on laboratory tests. False-positive Coombs test results may occur during treatment with cefotaxime. This phenomenon may interfere with cross-matching of blood. False-positive results may also occur when testing for glucose in urine using the reduction method. To avoid this, an enzymatic test should be used.

Alcohol should not be consumed during treatment, as disulfiram-like effects may occur (facial flushing, abdominal cramps, nausea, vomiting, headache, hypotension, tachycardia, respiratory difficulty).

Sodium. Each gram of the drug contains approximately 0.048 g of sodium, which should be taken into account in patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

The use of this medicinal product during pregnancy is contraindicated.

Use in women of childbearing potential requires careful assessment of expected benefits versus potential risks.

Cefotaxime passes into breast milk. An effect on the infant’s normal intestinal flora cannot be excluded, which may lead to diarrhea, colonization with yeast-like fungi, or sensitization of the child.

Therefore, a decision must be made whether to discontinue breastfeeding temporarily or to discontinue therapy permanently, weighing the benefits of breastfeeding for the child against the benefits of treatment for the mother.

Ability to affect reaction speed when driving or operating machinery.

Due to the possibility of nervous system adverse reactions, driving or operating machinery should be avoided during treatment.

Administration and Dosage

Cefotaxime-BHFS is administered intramuscularly and intravenously, by bolus injection or by infusion.

Treatment may be initiated before the results of antibiotic susceptibility testing are available. Cefotaxime exerts a synergistic effect when used in combination with aminoglycosides.

Dosage

The dosage and route of administration depend on the severity of infection, microbial susceptibility, and the patient's condition.

Duration of Treatment

The duration of treatment with Cefotaxime-BHFS depends on the clinical condition of the patient and the course of the disease.

Treatment should last for at least 10 days if the infection is caused by Streptococcus pyogenes (parenteral therapy may be switched to oral therapy before completion of the 10-day period).

Adults and adolescents (aged 12 to 16–18 years)

The usual dose is 1 g of cefotaxime every 12 hours. In severe infections, the daily dose may be increased up to 12 g. Daily doses up to 6 g can be divided into at least two separate doses administered at 12-hour intervals. Higher daily doses should be divided into at least three or four separate doses administered at 8- or 6-hour intervals, respectively.

The table below may serve as a guide for dosage.

Type of infection	Single dose of cefotaxime	Interval between administrations of the drug	Daily dose of cefotaxime
Typical infections in which microbial sensitivity has been demonstrated or is expected	1 g	12 hours	2 g
Infections in which high or moderate sensitivity of various microorganisms has been demonstrated or is expected	2 g	12 hours	4 g
Bacterial diseases of unclear etiology that cannot be localized and in which the patient's condition is critical	2-3 g	8 hours 6 hours	6-9 g 8-12 g

Infants and children (from 28 days to 11 years of age)

Usually 50–100 mg/kg body weight per day, depending on the severity of the infection (up to 150 mg), divided into 2–4 equal doses (every 12–6 hours).

The table below may serve as a guide for dosing.

Type of infection	Interval between administrations of the drug	Daily dose of cefotaxime
Typical infections where microbial sensitivity has been demonstrated or is expected	6-12 hours	50 mg/kg
Infections where high or moderate sensitivity of various microorganisms has been demonstrated or is expected	6-12 hours	100 mg/kg
Bacterial diseases of unclear etiology that cannot be localized and where the patient's condition is critical	6-8 hours	150 mg/kg*

*In exceptional cases, especially if there is a life-threatening situation, it may be necessary to increase the daily dose up to 200 mg/kg body weight per day. However, the maximum daily dose of 12 grams should not be exceeded.

Preterm and full-term newborns (aged 0–27 days)

Usually 50 mg/kg body weight per day, divided into 2–4 equal doses (every 12–6 hours). In life-threatening situations, an increase in the daily dose may be required. For severe infections, a dose of 150 mg/kg body weight per day is administered.

The table below can serve as a guide for dosing.

Type of infection	Age	Interval between doses of the drug	Daily dose of cefotaxime
Typical infections caused by susceptible microorganisms, or cases where high or moderate sensitivity has been demonstrated or is expected	0–7 days 8 days – 1 month	6–12 hours	50 mg/kg
Bacterial diseases of unknown etiology that cannot be localized and where the patient's condition is critical	0–7 days 8 days – 1 month	6–12 hours	100 mg/kg* 150 mg/kg*

*In exceptional cases, especially if life-threatening, the daily dose may be increased up to 200 mg/kg body weight per day. This dose should not be exceeded due to the immature renal excretory function in newborns (parameter: endogenous creatinine clearance).

Elderly patients

No dose adjustment is required in patients with normal renal and hepatic function.

Patients with renal impairment

In patients with creatinine clearance less than 10 mL/min, after the initial standard dose, maintenance doses should be reduced to half the standard dose without changing the dosing interval.

Patients undergoing hemodialysis: 1 to 2 g per day, depending on the severity of infection. On the day of hemodialysis procedure, cefotaxime should be administered after completion of the dialysis session.

Patients undergoing peritoneal dialysis: 1 to 2 g per day, depending on the severity of infection. Cefotaxime is not removed by peritoneal dialysis.

Other recommendations

Gonorrhea

Single dose (intramuscular or intravenous) of 0.5 g to 1 g of cefotaxime. In case of complicated infections, official guidelines should be followed. Syphilis should be ruled out before initiating treatment.

Urinary tract infections

In uncomplicated urinary tract infections: 1 g every 12 hours.

Bacterial meningitis

Adults: recommended daily doses of 6 to 12 g, divided into equal doses every 6–8 hours. Children: recommended daily doses of 150 to 200 mg/kg body weight per day, divided into equal doses every 6–8 hours. Newborns from day 1 to day 7 of life may receive 50 mg/kg body weight of cefotaxime every 12 hours; newborns from day 7 to day 28 of life – 50 mg/kg body weight every 8 hours.

Intra-abdominal infections

Intra-abdominal infections should be treated with cefotaxime in combination with other appropriate antibiotics.

Perioperative prophylaxis

For perioperative prophylaxis of infectious complications, a single dose of 1 to 2 g of cefotaxime is recommended 30–60 minutes before the start of surgery. An additional antibiotic is required to provide protection against anaerobic microorganisms. If the surgery lasts longer than 90 minutes, an additional dose is needed.

Administration method

Cefotaxime and aminoglycosides should not be mixed in the same syringe or infusion solution.

Preparation of solutions must be performed under aseptic (sterile) conditions. Use immediately after preparation.

Intramuscular administration

Dissolve 500 mg of Cefotaxime-BHPhZ in 2 mL, and 1000 mg in 4 mL of sterile water for injection or 1% lidocaine solution, and inject deeply into the gluteal muscle. When lidocaine is used, intravenous administration is strictly contraindicated.

Intravenous administration

Dissolve 500 mg of Cefotaxime-BHPhZ in 4 mL, 1000 mg in 8 mL, and 2000 mg in 10 mL of sterile water for injection. The solution should be injected slowly over 3–5 minutes, as life-threatening arrhythmias may occur when cefotaxime is administered via central venous catheter.

Intravenous infusion

Dissolve 1000–2000 mg of the drug in 40–100 mL of 0.9% isotonic sodium chloride solution or 5% glucose solution and administer over 50–60 minutes.

Children.

The drug should not be administered intramuscularly to children under 2.5 years of age.

Overdose.

Symptoms: possible fever, leukopenia, thrombocytopenia, acute hemolytic anemia, skin, gastrointestinal and hepatic reactions, dyspnea, renal failure, stomatitis, anorexia, temporary hearing loss, disorientation, seizures, encephalopathy (especially in patients with renal impairment).

Treatment: no specific antidote is available. Serum levels of cefotaxime can be reduced by hemodialysis. Peritoneal dialysis is ineffective in removing cefotaxime. Symptomatic therapy should be administered as needed.

In case of anaphylactic shock, appropriate measures should be taken immediately. If signs of hypersensitivity reaction occur (skin rash, urticaria, headache, nausea, loss of consciousness), administration of cefotaxime should be discontinued. In case of severe hypersensitivity reaction or anaphylactic reaction, appropriate therapy should be initiated (administration of epinephrine and/or glucocorticoids). Additional measures may be required in these clinical conditions, such as artificial ventilation, administration of histamine receptor antagonists. In case of circulatory failure, resuscitation measures should be initiated.

Side effects

Infections and parasitic diseases: superinfection.

Blood and lymphatic system: leukopenia, eosinophilia, thrombocytopenia, bone marrow suppression, pancytopenia, neutropenia, agranulocytosis, hemolytic anemia.

Immune system: Jarisch-Herxheimer reaction; anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock, malaise.

Nervous system: seizures, headache, dizziness, reversible encephalopathy, increased fatigue, weakness.

Heart: arrhythmia (with rapid intravenous infusion).

Gastrointestinal tract: nausea, vomiting, diarrhea, flatulence, abdominal pain, dysbiosis, stomatitis, glossitis, pseudomembranous colitis.

Hepatobiliary system: increased levels of liver transaminases, lactate dehydrogenase, alkaline phosphatase, and bilirubin; hepatitis, acute liver failure, liver dysfunction, jaundice, cholestasis.

Skin and subcutaneous tissue: hypersensitivity reactions including erythema, rash, pruritus, urticaria, acute generalized exanthematous pustulosis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), erythema.

Renal and urinary system: renal dysfunction/increased creatinine concentration (especially when used concomitantly with aminoglycosides), oliguria, acute renal failure, interstitial nephritis.

Local reactions: pain and infiltration at injection site (with intramuscular administration), fever, inflammatory reactions at injection site such as phlebitis/thrombophlebitis.

Jarisch-Herxheimer reaction

During treatment of infections caused by spirochetes, including Lyme disease, the Jarisch-Herxheimer reaction may develop within the first days of therapy. The following symptoms, either singly or in combination, have been reported within several weeks of treatment for Lyme disease: skin rash, pruritus, fever, leukopenia, elevated liver enzymes, dyspnea, joint discomfort.

Encephalopathy

Administration of high doses of beta-lactam antibiotics, including cefotaxime, particularly in patients with renal impairment, may lead to encephalopathy (with symptoms such as altered/loss of consciousness, abnormal movements, confusion, and seizures).

Hepatobiliary disorders

Elevations in liver enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase) and/or bilirubin have been observed.

These laboratory parameters may sometimes exceed the upper limit of normal by up to two times, indicating liver dysfunction, usually cholestatic in nature and often asymptomatic.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after the medicine has been authorized. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any adverse reactions via the national pharmacovigilance system.

Shelf life. 2 years.

After reconstitution, the solution may be stored for up to 24 hours in a refrigerator at 5±3 °C in a light-protected container, and for 12 hours at room temperature (20±5 °C) without light protection.

From a microbiological standpoint, the reconstituted solution should be used immediately. If not used immediately, the responsibility for storage conditions and duration lies with the user.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children!

Incompatibilities.

The drug solution is incompatible with aminoglycoside solutions in the same syringe or infusion (see also section "Interaction with other medicinal products and other forms of interaction"). Use only the diluents specified in the section "Method of administration and dosage".

Packaging. Vial №1 (without carton): 55 vials per box; vial №1 (in carton): 1 vial per carton; vial №1 (in carton): 1 vial with 5 ml solvent (water for injections) in an ampoule, packaged together with a cardboard divider in a carton.

Prescription status. Prescription only.

Manufacturer. Public Joint-Stock Company "Scientific and Production Center "Borshchahivskiy Chemical and Pharmaceutical Plant".

Manufacturer's address and location of operations.

17 Myru Street, Kyiv, 03134, Ukraine.