Merobocid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MERBOCID (MERBOCID)

Composition:

Active substance: meropenem;

1 vial of powder contains 500 mg or 1000 mg of meropenem (as sterile meropenem trihydrate);

Excipient: anhydrous sodium carbonate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white powder or white with a yellowish tint, or light yellow in color.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Carbapenems. ATC code J01D H02.

Pharmacological properties.

Pharmacodynamics.

Meropenem exerts a bactericidal effect by inhibiting the synthesis of bacterial cell walls in Gram-positive and Gram-negative bacteria through binding to penicillin-binding proteins (PBPs).

As with other beta-lactam antibacterial agents, the duration of time during which meropenem concentrations exceed the minimum inhibitory concentrations (MIC) (T > MIC) has shown a high degree of correlation with efficacy. In preclinical models, meropenem demonstrated activity at plasma concentrations exceeding the MIC for infecting microorganisms for approximately 40% of the dosing interval. This target value has not been clinically established.

Bacterial resistance to meropenem may develop due to: (1) reduced permeability of the outer membrane of Gram-negative bacteria (due to decreased porin production), (2) reduced affinity for target PBPs, (3) increased expression of efflux pump components, and (4) production of beta-lactamases capable of hydrolyzing carbapenems.

In the European Union, outbreaks of infection caused by carbapenem-resistant bacteria have been reported.

Cross-resistance between meropenem and medicinal products belonging to the classes of quinolones, aminoglycosides, macrolides, and tetracyclines is absent with regard to target microorganisms. However, bacteria may exhibit resistance to more than one class of antibacterial agents when the underlying mechanism involves reduced membrane permeability and/or presence of efflux pump(s).

The MIC breakpoints established during clinical studies by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are listed below.

Table 1

Microorganism	Susceptible (S), (mg/l)	Resistant (R), (mg/l)
Enterobacteriaceae	≤ 2	> 8
Pseudomonas species	≤ 2	> 8
Acinetobacter species	≤ 2	> 8
Streptococcus groups A, B, C, G	Note 6	Note 6
Streptococcus pneumoniae1	≤ 2	> 2
Other streptococci2	≤ 2	> 2
Enterococcus species
Staphylococcus species	Note 3	Note 3
Haemophilus influenzae1,2 and Moorella catarrhalis2	≤ 2	> 2
Neisseria meningitidis2,4	≤ 0.25	> 0.25
Gram-positive anaerobes, excluding Clostridium difficile	≤ 2	> 8
Gram-negative anaerobes	≤ 2	> 8
Listeria monocytogenes	≤ 0.25	> 0.25
Non-species related breakpoints5	≤ 2	> 8

1The breakpoint values of meropenem for Streptococcus pneumoniae and Haemophilus influenzae in meningitis are 0.25 mg/L (susceptible) and 1 mg/L (resistant).

2Microorganism strains with MIC values exceeding the S/R breakpoint values are very rare or have not yet been reported. Susceptibility testing for any such isolate must be repeated, and if the result is confirmed, the isolate should be referred to a reference laboratory. Until clinical response data are available for verified isolates with MIC values above the current resistance breakpoints (indicated in italics), such isolates should be reported as resistant.

3Staphylococcal susceptibility to carbapenems is predicted based on susceptibility to cefoxitin.

4Breakpoints apply only to meningitis.

5Non-species-specific breakpoints were primarily established based on PK/PD data and do not depend on the MIC distribution of individual species. They are intended for use with species not listed in the table and footnotes. Non-species-specific breakpoints are based on the following dosing regimens: EUCAST breakpoints apply to a meropenem dose of 1000 mg administered intravenously three times daily over 30 minutes as the lowest dose. Doses of 2 g three times daily were considered for severe infections and for intermediate/resistant breakpoints.

6Beta-lactam susceptibility of streptococcal groups A, B, C, and G is predicted based on penicillin susceptibility.

"–" Susceptibility testing is not recommended, as the organism is a poor target for treatment with this medicinal product. Isolates may be classified as resistant without prior testing.

The prevalence of acquired resistance may vary geographically and over time for individual species; therefore, it is advisable to refer to local data on microbial resistance, especially when treating severe infections. If necessary, when the local prevalence of microbial resistance is such that the benefit of using the medicinal product, at least for certain types of infections, is questionable, expert consultation should be sought.

The following lists pathogenic microorganisms based on clinical experience and therapeutic treatment guidelines.

Typically susceptible species

Gram-positive aerobes: Enterococcus faecalis⁷; Staphylococcus aureus (methicillin-susceptible)⁸; Staphylococcus species (methicillin-susceptible), including Staphylococcus epidermidis; Streptococcus agalactiae (group B); Streptococcus milleri group (S. anginosus, S. constellatus, and S. intermedius); Streptococcus pneumoniae; Streptococcus pyogenes (group A).

Gram-negative aerobes: Citrobacter freudii; Citrobacter koseri; Enterobacter aerogenes; Enterobacter cloacae; Escherichia coli; Haemophilus influenzae; Klebsiella oxytoca; Klebsiella pneumoniae; Morganella morganii; Neisseria meningitidis; Proteus mirabilis; Proteus vulgaris; Serratia marcescens.

Gram-positive anaerobes: Clostridium perfringens; Peptoniphilus asaccharolyticus; Peptostreptococcus species (including P. micros, P. anaerobius, P. magnus).

Gram-negative anaerobes: Bacteroides caccae; Bacteroides fragilis group; Prevotella bivia; Prevotella disiens.

Species for which acquired resistance may be a problem

Gram-positive aerobes: Enterococcus faecium^7,9.

Gram-negative aerobes: Acinetobacter species; Burkholderia cepacia; Pseudomonas aeruginosa.

Inherently resistant microorganisms

Gram-negative aerobes: Stenotrophomonas maltophilia; Legionella species.

Other microorganisms: Chlamydophila pneumoniae; Chlamydophila psittaci; Coxiella burnetii; Mycoplasma pneumoniae.

7Species exhibiting intrinsic intermediate susceptibility.

8All methicillin-resistant staphylococci are resistant to meropenem.

9Resistance rate > 50% in one or more EU countries.

Glanders and melioidosis: The use of meropenem in humans is based on susceptibility data for B. mallei and B. pseudomallei and limited human data. Physicians should refer to national and/or international consensus documents regarding the treatment of glanders and melioidosis.

Pharmacokinetics

In healthy volunteers, the mean elimination half-life from plasma is approximately 1 hour; the mean volume of distribution is approximately 0.25 L/kg (11–27 L); mean clearance is 287 mL/min following a 250 mg dose, decreasing to 205 mL/min with a 2 g dose. Doses of 500, 1000, and 2000 mg administered as a 30-minute infusion yield mean Cmax values of approximately 23, 49, and 115 µg/mL, respectively; corresponding AUC values are 39.3, 62.3, and 153 µg×h/mL. Following 5-minute infusions of 500 and 1000 mg, Cmax values are 52 and 112 µg/mL, respectively. With multiple dosing every 8 hours in patients with normal renal function, no accumulation of meropenem was observed.

In a study involving 12 patients who received meropenem 1000 mg every 8 hours after surgery for intra-abdominal infection, Cmax and elimination half-life values were consistent with those in healthy subjects, but the volume of distribution was larger (27 L).

Distribution

The mean plasma protein binding of meropenem is approximately 2% and is independent of drug concentration. After rapid administration (5 minutes or less), the pharmacokinetics are biexponential, but this becomes much less evident after a 30-minute infusion. Meropenem has been shown to penetrate well into various body fluids and tissues, including lungs, bronchial secretions, bile, cerebrospinal fluid, female genital tract tissues, skin, fascia, muscle, and peritoneal exudate.

Metabolism

Meropenem is metabolized via hydrolysis of the beta-lactam ring, forming a microbiologically inactive metabolite. In vitro, meropenem shows reduced susceptibility to hydrolysis by human dehydropeptidase-I (DHP-I) compared to imipenem, thus eliminating the need for co-administration of a DHP-I inhibitor.

Excretion

Meropenem is primarily excreted unchanged by the kidneys; approximately 70% (50–75%) of the dose is excreted unchanged within 12 hours. An additional 28% is excreted as the microbiologically inactive metabolite. Fecal excretion accounts for only about 2% of the dose. Measured renal clearance and the effect of probenecid indicate that meropenem undergoes both glomerular filtration and tubular secretion.

Renal impairment

Renal dysfunction leads to increased AUC in plasma and prolonged elimination half-life of meropenem. AUC increased by 2.4-fold in patients with moderate renal impairment (creatinine clearance (CrCl) 33–74 mL/min), by 5-fold in severe renal impairment (CrCl 4–23 mL/min), and by 10-fold in patients on hemodialysis (CrCl < 2 mL/min), compared to healthy volunteers (CrCl > 80 mL/min). AUC of the microbiologically inactive open-ring metabolite was also significantly increased in patients with renal impairment. Dose adjustment is recommended for patients with moderate to severe renal impairment (see section "Dosage and administration").

Meropenem is removed by hemodialysis, with a clearance during hemodialysis approximately 4 times higher than in anuric patients.

Hepatic impairment

Studies in patients with alcoholic liver cirrhosis show no effect of liver disease on meropenem pharmacokinetics after repeated dosing.

Adult patients

Pharmacokinetic studies in patients have not revealed significant pharmacokinetic differences compared to healthy volunteers with similar renal function. A population model developed from data in 79 patients with intra-abdominal infection or pneumonia showed that central volume of distribution depends on body weight, and clearance depends on creatinine clearance and age.

Children

Pharmacokinetic studies in infants and children with infection receiving doses of 10, 20, and 40 mg/kg demonstrated Cmax values approaching those in adults after 500, 1000, and 2000 mg doses, respectively. Comparison showed that pharmacokinetic parameters between doses and half-lives are similar to those in adults, except in the youngest patients (< 6 months, t_1/2 1.6 hours). Mean meropenem clearance values were 5.8 mL/min/kg (6–12 years), 6.2 mL/min/kg (2–5 years), 5.3 mL/min/kg (6–23 months), and 4.3 mL/min/kg (2–5 months). Approximately 60% of the dose is excreted in urine as meropenem and an additional 12% as metabolite within 12 hours. Meropenem concentrations in cerebrospinal fluid in children with meningitis are approximately 20% of simultaneous plasma levels, although considerable inter-individual variability exists.

Pharmacokinetics of meropenem in neonates receiving antibacterial treatment demonstrated higher clearance in neonates with greater chronological or gestational age, with an overall mean half-life of 2.9 hours. Monte Carlo simulations based on the population PK model showed that with a dosing regimen of 20 mg/kg every 8 hours, T > MIC of 60% against P. aeruginosa was achieved in 95% of preterm neonates and 91% of term neonates.

Elderly patients

Pharmacokinetic studies in healthy elderly volunteers (65–80 years) showed reduced plasma clearance, correlating with age-related reduction in creatinine clearance, and a slight decrease in non-renal clearance. Dose adjustment in elderly patients is not required, except in cases of moderate to severe renal impairment.

Clinical characteristics.

Indications.

Treatment of infections in adults and children aged 3 months and older, such as:

• pneumonia, including community-acquired and hospital-acquired pneumonia;
• bronchopulmonary infections in cystic fibrosis;
• complicated urinary tract infections;
• complicated intra-abdominal infections;
• infections during childbirth and postpartum infections;
• complicated skin and soft tissue infections;
• acute bacterial meningitis.

Meropenem may be used to treat patients with neutropenia and fever suspected of having a bacterial infection.

Treatment of patients with bacteremia associated or potentially associated with any of the above-mentioned infections.

Official recommendations on antibiotic therapy and guidelines for prevention of antibiotic resistance should be followed.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Hypersensitivity to any other antibacterial agent of the carbapenem group.

Severe hypersensitivity reactions (e.g., anaphylactic reactions, severe skin reactions) to any other type of beta-lactam antibacterial agent (e.g., penicillins or cephalosporins).

Interaction with other medicinal products and other forms of interaction.

Studies on the interaction of meropenem with individual medicinal products, except probenecid, have not been conducted.

The potential effect of meropenem on protein binding of other drugs or metabolism has not been studied. However, since protein binding is so minimal, interactions with other compounds via this mechanism are not expected.

Probenecid competes with meropenem for active tubular secretion and thus inhibits renal excretion of meropenem, resulting in an increased elimination half-life and elevated plasma concentrations of meropenem. Caution should be exercised when probenecid is administered concomitantly with meropenem.

Concomitant administration of carbapenems with valproic acid has been associated with a 60–100% reduction in valproic acid blood levels within approximately two days. Due to the rapid onset and extent of this reduction, concomitant use of valproic acid/sodium valproate/valpromide and carbapenems is not considered manageable and should be avoided (see section "Special precautions for use").

Concomitant use of antibiotics with oral anticoagulants, including warfarin, may enhance the anticoagulant effect of warfarin. Numerous reports have documented increased anticoagulant effects of oral anticoagulants, including warfarin, in patients receiving antibiotics concomitantly. The risk may vary depending on the underlying infection, age, and general condition of the patient, making it difficult to assess the exact contribution of antibiotics to the increase in INR (International Normalized Ratio). Frequent monitoring of INR is recommended during and shortly after concomitant use of antibiotics with oral anticoagulants.

Special precautions for use

When selecting meropenem for treatment, consideration should be given to the appropriateness of using a carbapenem-class antibacterial agent, taking into account factors such as the severity of infection, prevalence of resistance to other appropriate antibacterial agents, and the risk of selecting for carbapenem-resistant bacteria.

Resistance of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter

Resistance of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter to penems varies across the European Union. When prescribing the drug, local resistance patterns of these bacteria to penems should be taken into account.

Hypersensitivity reactions

As with other beta-lactam antibiotics, serious, and sometimes fatal, hypersensitivity reactions have been reported (see sections "Contraindications" and "Side effects").

Patients with a history of hypersensitivity to carbapenems, penicillins, or other beta-lactam antibiotics may also be at increased risk of hypersensitivity to meropenem. A thorough patient history regarding previous hypersensitivity reactions to beta-lactam antibiotics should be obtained before initiating meropenem therapy.

If a severe allergic reaction occurs, administration of the drug should be discontinued immediately and appropriate measures should be taken.

Severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), and acute generalized exanthematous pustulosis have been reported during meropenem treatment (see section "Side effects"). If signs or symptoms suggestive of these reactions occur, meropenem should be discontinued immediately and alternative therapy considered.

Antibiotic-associated colitis

Cases of antibiotic-associated colitis, including pseudomembranous colitis, with severity ranging from mild to life-threatening, have been reported with the use of nearly all antibacterial agents, including meropenem. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after meropenem therapy (see section "Side effects"). Discontinuation of meropenem therapy and initiation of specific treatment directed against Clostridium difficile should be considered. Medicinal products that inhibit intestinal motility should not be prescribed.

Seizures

Seizure episodes have been reported rarely during treatment with carbapenems, including meropenem (see section "Side effects").

Liver function monitoring

Due to the risk of hepatotoxicity (e.g., liver function abnormalities with cholestasis and cytolysis) during meropenem treatment, liver function should be closely monitored (see section "Side effects").

Use in patients with liver disease: liver function should be monitored in patients with pre-existing liver disease during meropenem treatment. Dose adjustment is not required (see section "Dosage and administration").

Seroconversion in the direct antiglobulin test (Coombs test)

Meropenem therapy may result in a positive direct or indirect Coombs test.

Concomitant administration of meropenem and valproic acid/sodium valproate/valpromide is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Merobocid contains approximately 2.0 mEq or 4.0 mEq of sodium per 500 mg or 1000 mg dose of the drug, respectively. This should be taken into account when prescribing the drug to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding

Data on the use of meropenem in pregnant women are lacking or limited in number. Animal studies have not revealed direct or indirect effects on reproductive toxicity.

As a precautionary measure, it is advisable to avoid using meropenem during pregnancy.

A small amount of meropenem passes into human breast milk. Meropenem may be used in breastfeeding women only if the expected benefit to the mother outweighs the potential risk to the infant.

Ability to affect reaction speed when driving or operating machinery

Studies on the effect of meropenem on the ability to drive or operate machinery have not been conducted.

However, when driving or operating machinery, particular caution is recommended due to the possibility of headache, paresthesia, or seizures, which have been reported during meropenem use.

Dosage and administration.

The tables below provide general recommendations for dosing of the medicinal product.

The dose of Merobocid and duration of treatment depend on the type of causative agent of the disease, severity of the infection, and the clinical response to therapy.

Merobocid, when administered at a dose of up to 2 g three times daily in adults and children with body weight over 50 kg, and at a dose of up to 40 mg/kg three times daily in children, may be particularly appropriate for the treatment of certain infections caused by less susceptible bacterial species (e.g., Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter), or in cases of very severe infections.

Additional dosage recommendations must be followed when treating patients with renal impairment (see Table 3).

Table 2

Recommended doses for adults and children with body weight over 50 kg

Infection	Single dose administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired pneumonia	500 mg or 1 g
Brucopulmonary infections in cystic fibrosis	2 g
Complicated urinary tract infections	500 mg or 1 g
Complicated intra-abdominal infections	500 mg or 1 g
Infections during childbirth and postpartum infections	500 mg or 1 g
Complicated skin and soft tissue infections	500 mg or 1 g
Acute bacterial meningitis	2 g
Treatment of patients with febrile neutropenia	1 g

Meropenem is usually administered by intravenous infusion over 15 to 30 minutes.

Additionally, doses of up to 1 g may be given as an intravenous bolus injection over approximately 5 minutes. Safety data regarding administration of the 2 g dose as an intravenous bolus injection in adults are limited.

Renal impairment

Table 3

Recommended doses of the drug for adults and children with body weight over 50 kg with creatinine clearance less than 51 ml/min

Creatinine clearance (ml/min)	Dose (see table 1)	Frequency
26-50	full dose	every 12 hours
10-25	half dose	every 12 hours
<10	half dose	every 24 hours

There is limited data available on the use of these adjustments for a single dose of 2 g.

Meropenem is removed by hemodialysis and hemofiltration; therefore, the required dose of the drug should be administered after completion of the hemodialysis procedure.

There are no dosage recommendations for patients undergoing peritoneal dialysis.

Hepatic impairment

Dosage adjustment of the drug is not required in patients with hepatic impairment.

Elderly patients

Dosage adjustment is not required in elderly patients with normal renal function or with creatinine clearance values above 50 ml/min.

Children under 3 months of age

The safety and efficacy of meropenem in children under 3 months of age have not been established, and the optimal dosing regimen has not been determined.

Table 4

Recommended doses of the drug in children aged from 3 months to 11 years with body weight up to 50 kg

Infection	Dose administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired	10 or 20 mg/kg body weight
Respiratory tract infections in cystic fibrosis	40 mg/kg body weight
Complicated urinary tract infections	10 or 20 mg/kg body weight
Complicated intra-abdominal infections	10 or 20 mg/kg body weight
Complicated skin and soft tissue infections	10 or 20 mg/kg body weight
Acute bacterial meningitis	40 mg/kg body weight
Treatment of patients with febrile neutropenia	20 mg/kg body weight

Merobocide is usually administered as an intravenous infusion lasting from 15 to 30 minutes. Additionally, doses of meropenem up to 20 mg/kg may be administered as an intravenous bolus injection over approximately 5 minutes. Safety data regarding administration of the drug as an intravenous bolus injection in children at a dose of 40 mg/kg are limited.

Children with body weight over 50 kg

The dose should be administered as for adult patients.

There is no experience with the use of the drug in children with impaired renal function.

Administration of intravenous bolus injection

The solution for bolus injection should be prepared by dissolving Merobocide in water for injections to obtain a concentration of 50 mg/mL.

Chemical and physical stability of the prepared solution for bolus injection is maintained for 3 hours at temperatures from 15 to 25 °C.

From a microbiological standpoint, the medicinal product should be used immediately after preparation.

If the medicinal product is not used immediately, the storage time and conditions of the prepared solution should be carefully controlled.

Administration of intravenous infusion

The infusion solution should be prepared by dissolving Merobocide in 0.9% sodium chloride infusion solution or in 5% glucose (dextrose) infusion solution to obtain a concentration of 1–20 mg/mL.

Chemical and physical stability of the prepared infusion solution using 0.9% sodium chloride solution is maintained for 3 hours at temperatures from 15 to 25 °C or for 24 hours at 2–8 °C. The prepared solution, if cooled, should be used within 2 hours after removal from the refrigerator.

From a microbiological standpoint, the medicinal product should be used immediately after preparation.

If the medicinal product is not used immediately, the storage time and conditions of the prepared solution should be carefully controlled.

The Merobocide solution prepared with 5% glucose (dextrose) solution should be used immediately.

Prepared solutions should not be frozen.

Children.

The drug is administered to children aged from 3 months.

Overdose.

Relative overdose is possible in patients with impaired renal function if the drug dose is not adjusted as described in the section "Dosage and administration". Experience from post-marketing use of meropenem is limited. If adverse reactions occurred after overdose, they were consistent with the adverse reaction profile of meropenem (see section "Adverse reactions"), were usually of mild severity, and resolved after discontinuation of the drug or dose reduction.

Treatment: symptomatic therapy. In patients with normal renal function, the drug is rapidly eliminated by the kidneys. Meropenem and its metabolites are removed from the body by hemodialysis.

Adverse reactions.

In a review of data on the impact of meropenem in 4872 out of 5026 patients, the most commonly reported adverse reactions associated with its use were diarrhea (2.3%), rash (1.4%), nausea/vomiting (1.4%), and injection site inflammation (1.1%). The most frequently reported laboratory abnormalities associated with meropenem use were thrombocytosis (1.6%) and elevated levels of liver enzymes (1.5–4.3%).

Blood and lymphatic system: thrombocytosis, eosinophilia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia.

Immune system: hypersensitivity reactions, including angioedema, anaphylactic reactions (see sections "Contraindications", "Special precautions").

Psychiatric disorders: delirium.

Nervous system: headache, paresthesia, seizures (see section "Special precautions").

Gastrointestinal tract: diarrhea, vomiting, nausea, abdominal pain, antibiotic-associated colitis, including pseudomembranous colitis.

Hepatobiliary system: increased levels of transaminases, alkaline phosphatase, lactate dehydrogenase, and bilirubin in blood.

Skin and subcutaneous tissue: rash, pruritus, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), acute generalized exanthematous pustulosis (see section "Special precautions").

Renal and urinary system: increased levels of creatinine and blood urea.

Infections and infestations: oral and vaginal candidiasis.

General disorders and administration site conditions: inflammation, pain, thrombophlebitis, injection site pain.

Paediatric population. Based on limited available data, there is no evidence of increased risk of any adverse reactions in children. All reported events corresponded to adverse reactions observed in adult patients.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals should report any suspected adverse reactions in accordance with applicable legislation.

Shelf life. 3 years.

Do not use the medicine after the expiry date.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach and sight of children.

Each vial is for single use only.

Standard aseptic techniques should be used when preparing the solution and during administration.

Shake the solution well before use.

Any unused medicine or waste material must be disposed of in accordance with local requirements.

Incompatibilities.

Merobocid must not be mixed or added with other medicinal products.

Merobocid intended for intravenous bolus injection should be reconstituted with sterile water for injection.

Merobocid in vials for intravenous infusion may be directly reconstituted with 0.9% sodium chloride solution or 5% glucose solution for infusion.

Packaging. 500 mg or 1000 mg powder in a vial; 1 vial per pack.

Prescription status. Prescription only.

Manufacturer.

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

Manufacturer's address and location of its business activity.

17 Myru Street, Kyiv, 03134, Ukraine.