Demopenem®

INSTRUCTIONS for medical use of the medicinal product DEMOPENEM® (DEMOPENEM®)

Composition:

active substance: meropenem;

1 vial contains meropenem trihydrate equivalent to anhydrous meropenem 500 mg or 1000 mg;

excipient: sodium carbonate anhydrous.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: crystalline powder, white to pale yellow in colour.

Pharmacotherapeutic group.

Antibacterial 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 both Gram-positive and Gram-negative bacteria through binding to penicillin-binding proteins (PBP).

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 when plasma concentrations exceeded the MIC of the infecting microorganisms for approximately 40% of the dosing interval. This target value has not been established clinically.

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

Cases of infectious diseases caused by bacteria resistant to carbapenems have been reported.

Cross-resistance between meropenem and medicinal products belonging to the classes of quinolones, aminoglycosides, macrolides, and tetracyclines is absent, considering the target microorganisms. However, bacteria may exhibit resistance to more than one class of antibacterial agents when the mechanism involved includes impermeability of the cell membrane and/or presence of an efflux pump.

Table 1

MIC breakpoints determined during clinical studies by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

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 MoRaxella catarrhalis2	≤ 2	> 2
Neisseria meningitidis2,4	≤ 0.25	> 0.25
Gram-positive anaerobes, except Clostridium difficile	≤ 2	> 8
Gram-negative anaerobes	≤ 2	> 8
Listeria monocytogenes	≤ 0.25	> 0.25
Species-independent breakpoints5	≤ 2	> 8

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

2 Microorganism strains with MIC values exceeding the S/R breakpoint are very rare or have not been reported to date. Testing for identification and antimicrobial susceptibility of any such isolate should 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 exceeding the current resistance breakpoints, such isolates should be reported as resistant.

3 Susceptibility of staphylococci to meropenem is predicted based on susceptibility to cefoxitin.

4 The breakpoints apply only to meningitis.

5 Non-species-related breakpoints were primarily established based on pharmacokinetic and pharmacodynamic data and do not depend on the MIC distribution of individual species. They are intended for use with species not listed in Table 1 and footnotes. Non-species-related breakpoints are based on the following dosing regimens: EUCAST breakpoints apply to meropenem administered intravenously at 1000 mg 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.

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

«–» Performance of susceptibility testing is not recommended, as the organism is a poor target for the drug. Isolates may be designated as resistant without prior testing.

The prevalence of acquired resistance may vary geographically and over time for individual species; therefore, local data on microbial resistance should be taken into account, especially when treating severe infections. If necessary, when the local prevalence of 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 list of pathogenic microorganisms is based on clinical experience and therapeutic treatment guidelines.

Usually 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 freundii, 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.

7 Species exhibiting natural intermediate susceptibility.

8 All methicillin-resistant staphylococci are resistant to meropenem.

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

Glanders and melioidosis: the use of meropenem in humans is based on in vitro 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 plasma elimination half-life (t_1/2) is approximately 1 hour; the mean volume of distribution is approximately 0.25 L/kg (11–27 L); the mean clearance is 287 mL/min following a 250 mg dose, decreasing to 205 mL/min with a 2 g dose. Following 30-minute infusions of 500, 1000, and 2000 mg doses, mean peak concentrations (C_max) were approximately 23, 49, and 115 µg/mL, respectively; corresponding area under the concentration-time curve (AUC) values were 39.3, 62.3, and 153 µg×h/mL. After 5-minute infusions, C_max was 52 and 112 µg/mL following 500 and 1000 mg doses, respectively. No accumulation of meropenem was observed in patients with normal renal function receiving multiple doses every 8 hours.

In studies involving patients undergoing surgery for intra-abdominal infections who received meropenem 1000 mg every 8 hours, C_max and t_1/2 values were similar to those in healthy volunteers, but the volume of distribution was higher (27 L).

Distribution

The mean extent of 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 is much less evident after a 30-minute infusion. Meropenem has been shown to penetrate well into certain body fluids and tissues, including lung, bronchial secretions, bile, cerebrospinal fluid, female genital tract tissues, skin, fascia, muscle, and peritoneal exudates.

Metabolism

Meropenem is metabolized by 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, and there is no need for concomitant 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 probenecid effects indicate that meropenem undergoes both glomerular filtration and tubular secretion.

Renal impairment

Renal dysfunction results in higher plasma AUC values and a prolonged t_1/2 of meropenem. AUC values increased by 2.4-fold in patients with moderate renal impairment (creatinine clearance (CrCl) 33–74 mL/min), by 5-fold in patients with 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 values of the microbiologically inactive open-ring metabolite were also significantly increased in patients with renal impairment. Dose adjustment is recommended for patients with moderate to severe renal impairment.

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 cirrhosis of the liver show no influence of liver disease on the pharmacokinetics of meropenem after repeated dosing.

Adult patients

Pharmacokinetic studies in patients showed no significant pharmacokinetic differences compared to healthy volunteers with similar renal function. A population model developed based on data from patients with intra-abdominal infection or pneumonia showed dependence of key parameters on body weight, creatinine clearance, and age.

Children

Pharmacokinetic studies in infants and children with infection receiving doses of 10, 20, and 40 mg/kg demonstrated C_max values approaching those observed in adults after 500, 1000, and 2000 mg doses, respectively. Pharmacokinetic characteristics, dose-dependent t_1/2, were similar to those observed in all adults, except in younger 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 within 12 hours as meropenem and an additional 12% as metabolite. Meropenem concentrations in cerebrospinal fluid in children with meningitis are approximately 20% of simultaneously measured plasma levels, although there is considerable individual variability.

Pharmacokinetics of meropenem in neonates receiving antibacterial treatment showed higher clearance in neonates with greater chronological or gestational age, with an overall mean t_1/2 of 2.9 hours. Monte Carlo simulation based on the population PK model indicated 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 elderly healthy volunteers (65–80 years) showed reduced plasma clearance, correlating with age-related reduction in CrCl, as well as a slight reduction in non-renal clearance. Dose adjustment is not required for elderly patients, except in cases of moderate to severe renal impairment.

Clinical characteristics.

Indications.

The medicinal product is indicated for the treatment of infections in adults and children aged 3 months and older:

• 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.

The medicinal product may be used for the treatment of patients with neutropenia and fever suspected to be caused by a bacterial infection.

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

Official recommendations regarding the appropriate use of antibacterial agents should be taken into account.

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 (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 the medicinal product with individual medicinal products, except probenecid, have not been conducted.

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.

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

Reduced serum levels of valproic acid by 60–100% within approximately 2 days have been observed when co-administered with carbapenems. Due to the rapid onset and extent of this reduction, concomitant administration of valproic acid/sodium valproate/valpromide and carbapenems is considered non-adjustable; therefore, such combination should be avoided.

Oral anticoagulants

Concomitant use of antibiotics with warfarin may enhance its anticoagulant effect. Numerous reports have documented increased anticoagulant effect of anticoagulant agents, including warfarin, when administered orally to patients receiving antibacterial agents concomitantly. The risk may vary depending on the type of underlying infection, age, and general condition of the patient, making it difficult to assess the contribution of antibacterial agents to the increase in international normalized ratio (INR). Frequent monitoring of INR levels during and after concomitant use of antibiotics with oral anticoagulants is recommended.

Children

All drug interaction studies have been conducted in adults only.

Special precautions for use.

When selecting meropenem as a treatment option, 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 suitable antibacterial agents, and the risk of selecting for carbapenem-resistant bacteria.

Resistance of Enterobacteriaceae,Pseudomonas aeruginosa, and Acinetobacter

In the European Union, resistance to penems among Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter varies. 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.

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 assessment of prior hypersensitivity reactions to beta-lactam antibiotics should be conducted before initiating meropenem therapy.

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

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

Antibiotic-associated colitis

Cases of colitis, including pseudomembranous colitis, associated with antibiotic use have been reported with nearly all antibacterial agents, including meropenem, with severity ranging from mild to life-threatening. It is therefore important to consider this diagnosis in patients who develop diarrhea during or after meropenem therapy. Discontinuation of meropenem therapy and initiation of specific treatment against Clostridium difficile should be considered. Medications that inhibit intestinal motility should not be prescribed.

Seizures

Seizures have been rarely reported during treatment with carbapenems, including meropenem (see section "Adverse reactions").

Liver function monitoring

Due to the risk of hepatotoxicity (liver function abnormalities with cholestasis and cytolysis) during meropenem therapy, liver function should be closely monitored. Dose adjustment is not required.

Seroconversion in the direct antiglobulin test (Coombs test)

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

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

Demopenem® contains 46 mg of sodium per 500 mg vial and 92 mg of sodium per 1000 mg vial. Caution should be exercised when administering the drug to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of meropenem in pregnant women are lacking or limited in quantity.

Animal studies have not shown direct or indirect effects on reproductive toxicity. As a precautionary measure, it is advisable to avoid using meropenem during pregnancy.

Breastfeeding

It has been reported that small amounts of meropenem pass into human breast milk. Meropenem may be used during breastfeeding 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 the drug on the ability to drive or operate machinery have not been conducted. 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.

Method of administration and dosage.

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

The dose of meropenem and duration of treatment depend on the type of causative agent, severity of the disease, and individual patient sensitivity.

Demopenem® 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 effective in treating 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 below).

Table 2

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

Infection	Single dose to be administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired	500 mg or 1 g
Bronehopulmonary 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

Demopenem® is usually administered as an intravenous infusion lasting from 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 on administration of a 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 when patients' creatinine clearance is less than 51 ml/min

Creatinine clearance (ml/min)	Single dose (see table 2)	Frequency
26-50	full single dose	every 12 hours
10-25	half the single dose	every 12 hours
< 10	half the single dose	every 24 hours

Data supporting the use of the doses of the medicinal product indicated in Table 3, adjusted to the 2 g unit dose, are limited.

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

There are no dosage recommendations for patients undergoing peritoneal dialysis.

Hepatic impairment

Dose adjustment of the medicinal product is not required in patients with hepatic impairment.

Dosing in elderly patients

Dose adjustment is not required in elderly patients with normal renal function or with creatinine clearance (CrCl) values > 50 mL/min.

Children under 3 months of age

There are no data on the safety and efficacy of meropenem in children under 3 months of age, and the optimal dosing regimen has not been established. There are limited pharmacokinetic data supporting the use of a meropenem dose of 20 mg/kg every 8 hours (see section "Pharmacokinetics").

Table 4

Recommended doses of the medicinal product for children aged from 3 months to 11 years and with body weight less than 50 kg

Infection	Single dose to be administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired	10 mg/kg or 20 mg/kg body weight
Respiratory tract infections in cystic fibrosis	40 mg/kg body weight
Complicated urinary tract infections	10 mg/kg or 20 mg/kg body weight
Complicated intra-abdominal infections	10 mg/kg or 20 mg/kg body weight
Complicated skin and soft tissue infections	10 mg/kg 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

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

Children with body weight above 50 kg

The dose should be the same as for adult patients.

Method of administration

Demopenem® 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 for administration of the drug as an intravenous bolus injection at a dose of 40 mg/kg in children are limited.

Administration of intravenous bolus injection

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

Chemical and physical stability of the prepared bolus injection solution was maintained for 3 hours at room temperature (15–25 °C).

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

If the product is not used immediately, responsibility for storage duration and conditions after preparation lies with the physician.

Administration of intravenous infusion

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

Chemical and physical stability of the prepared infusion solution using 0.9% sodium chloride solution was maintained for 6 hours at room temperature (15–25 °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. If the product is not used immediately, responsibility for storage duration and conditions after preparation lies with the physician.

The prepared solution using 5% glucose (dextrose) solution should be used immediately, i.e., within 1 hour after preparation.

The vial is intended for single use only. Standard aseptic techniques should be used during solution preparation and administration. The solution should be shaken before use. Any unused solution or waste material should be disposed of in accordance with local requirements.

Children

The drug may be used in children aged from 3 months.

Overdose

Relative overdosage is possible in patients with impaired renal function if the dose of the drug is not adjusted. Available post-marketing experience indicates that if adverse reactions occur following overdosage, they are consistent with the profile of the adverse reactions listed below, are usually mild in severity, and resolve after discontinuation or dose reduction of the drug. Symptomatic treatment should be considered as necessary.

In individuals with normal renal function, the drug is rapidly eliminated by the kidneys.

Meropenem and its metabolites can be removed from the body by hemodialysis.

Adverse Reactions

The most commonly reported adverse reactions associated with meropenem administration were diarrhea, rash, nausea/vomiting, and injection site inflammation. The most frequently reported laboratory abnormalities associated with meropenem use were thrombocytosis and elevated liver enzymes.

The adverse reactions listed below are categorized by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from available data). Within each frequency group, adverse reactions are listed in order of decreasing severity.

Infections and infestations: uncommon – oral and vaginal candidiasis.

Blood and lymphatic system disorders: common – thrombocytopenia; uncommon – eosinophilia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia.

Immune system disorders: uncommon – angioedema, anaphylactic reactions (see sections "Contraindications" and "Special precautions").

Nervous system disorders: common – headache; uncommon – paresthesia; rare – seizures (see section "Special precautions").

Gastrointestinal disorders: common – nausea, vomiting, diarrhea, abdominal pain; uncommon – antibiotic-associated colitis (see section "Special precautions").

Hepatobiliary and biliary tract disorders: common – increased transaminase levels, increased alkaline phosphatase levels in blood, increased lactate dehydrogenase levels in blood; uncommon – increased blood bilirubin levels.

Skin and subcutaneous tissue disorders: common – rash, pruritus; uncommon – urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme (see section "Special precautions"); frequency not known – drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (see section "Special precautions").

Renal and urinary disorders: uncommon – increased blood creatinine and urea levels.

General disorders and administration site conditions: common – inflammation, pain; uncommon – thrombophlebitis, injection site pain.

There are no data suggesting an increased risk of adverse events in children based on the limited available data. All reported events corresponded to adverse reactions observed in adult patients.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions in accordance with applicable legislation.

Shelf life. 4 years.

Storage conditions.

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

Keep out of reach of children.

Incompatibilities.

Meropenem must not be mixed or added to other medicinal products.

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

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

Packaging.

1 vial per cardboard package.

Prescription category. Prescription only.

Manufacturer.

DEMO S.A. Pharmaceutical Industry.

Manufacturer's address and location of operations.

21st kilometer of the Athens-Lamia National Highway, Kryoneri Attica, 14568, Greece.