Meropenem - vista

INSTRUCTIONS for medical use of the medicinal product Meropenem-Vista (Meropenem-Vista)

Composition:

Active substance: meropenem;

1 vial contains 570 mg of meropenem trihydrate, equivalent to 500 mg of meropenem calculated as anhydrous substance;

1 vial contains 1140 mg of meropenem trihydrate, equivalent to 1000 mg of meropenem calculated as anhydrous substance;

1 vial contains 2280 mg of meropenem trihydrate, equivalent to 2000 mg of meropenem calculated as anhydrous substance;

Excipient: sodium carbonate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: powder from white to light yellow 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 the concentration of meropenem exceeds the minimum inhibitory concentration (MIC) correlates highly 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 established clinically.

Bacterial resistance to meropenem may develop due to:

• reduced permeability of the outer membrane of Gram-negative bacteria (due to decreased production of porins);
• reduced affinity for target PBPs;
• increased expression of efflux pump components;
• 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, with respect to the target microorganisms. However, bacteria may exhibit resistance to more than one class of antibacterial agents when the mechanism involved includes reduced membrane permeability and/or presence of efflux pump(s).

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	≤ 2	> 8
Acinetobacter	≤ 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-unrelated breakpoints5	≤ 2	> 8

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

2. Microbial strains with MIC values exceeding the S/R breakpoint values are very rare or have not yet been reported. Testing for identification and antimicrobial susceptibility for any such isolate should be repeated; if the result is confirmed, the isolate should be sent to a reference laboratory. Until data on clinical response for verified isolates with MIC values exceeding the current resistance breakpoints (indicated in italics) become available, such isolates should be reported as resistant.

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

4. Meropenem breakpoint values for Neisseria meningitidis apply only to meningitis.

5. Non-species-related breakpoint values were primarily determined based on pharmacokinetic (PK)/pharmacodynamic (PD) 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 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 breakpoint categories.

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

"—" Performing susceptibility testing is not recommended, as the organism is a poor target for treatment with this agent. Isolates may be classified as resistant without prior testing.

The prevalence of acquired resistance may vary geographically and over time for individual species; therefore, local information on microbial resistance should be taken into account, especially when treating severe infections. When necessary, and when the local prevalence of microbial resistance renders the benefit of using the medicinal product at least questionable for certain types of infections, consultation with an expert is recommended.

Below is a list of pathogenic microorganisms identified based on clinical experience and therapeutic treatment guidelines.

Typically susceptible species

Gram-positive aerobes

Enterococcus faecalis 7 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 that have demonstrated natural intermediate susceptibility.

8All methicillin-resistant staphylococci are resistant to meropenem.

9Resistance rate > 50 % in one or more European Union 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 clinical data. Physicians should consider national and/or international consensus guidelines regarding the treatment of glanders and melioidosis.

Pharmacokinetics.

In healthy volunteers, the mean elimination half-life (t1/2) from plasma is approximately 1 hour, the mean volume of distribution is about 0.25 L/kg (11–27 L), and the mean clearance is 287 mL/min following a 250 mg dose, decreasing to 205 mL/min with a 2 g dose. After administration of 500 mg, 1000 mg, and 2000 mg doses as 30-minute infusions, mean maximum plasma concentrations (Cmax) were approximately 23 µg/mL, 49 µg/mL, and 115 µg/mL, respectively; corresponding area under the concentration-time curve (AUC) values were 39.3 µg×h/mL, 62.3 µg×h/mL, and 153 µg×h/mL. Following 5-minute infusions, Cmax values were 52 µg/mL and 112 µg/mL for 500 mg and 1000 mg doses, respectively. With multiple dosing every 8 hours in patients with normal renal function, accumulation of meropenem was not observed.

In a study involving 12 patients who received meropenem 1000 mg every 8 hours after surgery for intra-abdominal infections, Cmax and t1/2 values were similar to those in healthy volunteers, but the volume of distribution (27 L) was higher.

Distribution.

Plasma protein binding of meropenem averages approximately 2 % and is independent of drug concentration. After rapid administration (5 minutes or less), the pharmacokinetics are biexponential, but this is much less pronounced 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 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 demonstrates reduced susceptibility to hydrolysis by human dehydropeptidase-I (DHP-I) compared to imipenem, and therefore co-administration with a DHP-I inhibitor is not required.

Elimination.

Meropenem is primarily excreted unchanged by the kidneys; approximately 70 % (50–75 %) of the administered 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. Renal clearance and the effect of probenecid indicate that meropenem undergoes both glomerular filtration and tubular secretion.

Renal impairment.

Renal impairment leads to increased plasma AUC and prolonged t1/2 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 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). The AUC of the microbiologically inactive open-ring metabolite also significantly increased in patients with renal impairment. Dose adjustment is recommended for patients with moderate and 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 cirrhosis showed no effect of liver disease on the pharmacokinetics of meropenem 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 dependence of key parameters on body weight, creatinine clearance, and patient age.

Children.

Pharmacokinetic studies in infants and children with infection receiving doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg demonstrated Cmax values approaching those observed in adults after 500 mg, 1000 mg, and 2000 mg doses, respectively. A pharmacokinetic relationship between dose and half-life similar to that in adults was observed, except in the youngest patients (< 6 months, t1/2 was 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 was 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 simultaneously measured plasma concentrations, although there is considerable inter-individual variability. Pharmacokinetics of meropenem in neonates receiving antibacterial therapy showed 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 pharmacokinetic 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, correlated with age-related reduction in creatinine clearance, and a slight decrease in non-renal clearance. Dose adjustment is not required for elderly patients unless moderate or severe renal impairment is present.

Clinical characteristics.

Indications.

Meropenem is indicated for the treatment of the following 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.

Meropenem may be used for the treatment of 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.

Consideration should be given to providing official guidance on the appropriate use of antibacterial agents.

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 agents (e.g., penicillins or cephalosporins).

Interaction with other medicinal products and other forms of interaction.

Studies on drug interactions 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, leading to an increased elimination half-life and higher plasma concentrations of meropenem. Caution should be exercised when probenecid is co-administered with meropenem. The potential effect of meropenem on protein binding or metabolism of other drugs has not been studied. However, since protein binding is so minimal, interactions with other compounds based on this mechanism are unlikely. Decreased blood levels of valproic acid have been reported when co-administered with carbapenems, approximately 60–100% within about 2 days. Due to the rapid onset and extent of this reduction, concomitant administration of valproic acid/sodium valproate/valpromide and carbapenems is considered non-adjustable and should therefore be avoided (see section "Special precautions for use"). Oral anticoagulants. Concomitant use of antibiotics with warfarin may enhance its anticoagulant effect. Numerous reports have documented increased anticoagulant effect of orally administered anticoagulants, including warfarin, in patients receiving antibacterial agents concomitantly. The risk may vary depending on the underlying infection, age, and general condition of the patient, making it difficult to assess the precise role of antibacterial agents in increasing the international normalized ratio (INR). Frequent monitoring of INR levels is recommended during and shortly after concomitant use of antibiotics with oral anticoagulants.

Children. All drug interaction studies have been conducted in adult patients 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 carbapenem-resistant bacterial strains.

Resistance in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter. In the European Union, resistance to penems among Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter varies. When prescribing this medicinal product, local resistance patterns of these bacteria to penems should be taken into account.

Hypersensitivity reactions.

Serious, and sometimes fatal, hypersensitivity reactions have been reported, as with other beta-lactam antibiotics (see sections "Contraindications" and "Undesirable effects").

Patients with a history of hypersensitivity to carbapenems, penicillins, or other beta-lactam antibiotics may also exhibit hypersensitivity to meropenem. A careful patient history regarding previous hypersensitivity reactions to beta-lactam antibiotics should be obtained prior to initiating therapy with meropenem.

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

Severe skin reactions have been reported in patients receiving meropenem, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), erythema multiforme, and acute generalized exanthematous pustulosis. 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 and pseudomembranous colitis, with severity ranging from mild to life-threatening, have been reported with nearly all antibacterial agents, including meropenem. It is therefore important to remain vigilant for patients who develop diarrhea during or after meropenem therapy (see section "Undesirable effects"). Discontinuation of meropenem therapy and initiation of specific treatment directed against Clostridium difficile should be considered. Medicinal products that inhibit intestinal peristalsis should not be administered.

Seizures.

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

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 (see section "Undesirable effects").

Use in patients with hepatic disease.

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

Serum conversion 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/valproate sodium/valpromide is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Important information about excipients.

The medicinal product Meropenem-Vista contains approximately 2.0 mEq, 4.0 mEq, or 8.0 mEq of sodium per vial for the 500 mg, 1 g, or 2 g dose, respectively. This should be taken into consideration when prescribing the product to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

Pregnancy.

Data on the use of meropenem in pregnant women are lacking or limited in number. 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 are excreted in 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 influence of the medicinal product on the ability to drive vehicles or operate machinery have not been conducted.

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

Dosage and Administration.

The dosage recommendations for the medicinal product are provided in Tables 2–4 below.

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

Meropenem 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, is most suitable for the treatment of certain infections caused by less susceptible bacterial species (e.g., Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter), or in cases of 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 administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired pneumonia	500 mg or 1 g
Respiratory tract 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
Presence of febrile neutropenia in patient	1 g

Meropenem should be administered as an intravenous infusion over a period of 15 to 30 minutes.

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

Renal impairment.

Table 3

Recommended doses of the drug for adults and children with body weight over 50 kg,

creatinine clearance 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 regarding the use of the doses of the drug indicated in Table 3, adjusted to the 2 g dose unit, are limited.

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 recommendations regarding the established dose of the drug for patients undergoing peritoneal dialysis.

Hepatic impairment.

Dose adjustment of the drug is not required for patients with hepatic impairment (see section "Special warnings and precautions for use").

Dosing in elderly patients.

Dose adjustment is not required for elderly patients with normal renal function or with creatinine clearance values above 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. Limited pharmacokinetic data support the use of a meropenem dose of 20 mg/kg every 8 hours (see section "Pharmacokinetics").

Table 4

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

Infection	Single 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

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

Children with a body weight above 50 kg should receive the adult dose. Method of administration.

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

Intravenous bolus injection.

The solution for bolus injection should be prepared by dissolving Meropenem-Vista medicinal product 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 up to 25°C or for 12 hours at 2–8°C.

From a microbiological standpoint, if the method of opening/reconstitution/dilution does not exclude the risk of microbial contamination, the medicinal product should be used immediately. If the medicinal product is not used immediately, the physician is responsible for the duration and conditions of storage after preparation.

Intravenous infusion.

The infusion solution should be prepared by dissolving the Meropenem-Vista medicinal product in 0.9% sodium chloride solution for infusion or in 5% glucose (dextrose) solution for infusion 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 3 hours at room temperature up to 25°C or for 24 hours at 2–8°C.

From a microbiological standpoint, the medicinal product should be used immediately. The meropenem solution prepared with 5% glucose (dextrose) solution should be used immediately. Prepared solutions should not be frozen.

Children.

The drug may be administered to children aged from 3 months.

Overdose.

Relative overdose is possible in patients with impaired kidney function if the drug dose is not adjusted.

Symptoms. Limited post-marketing experience indicates that adverse reactions occurring after overdose are consistent with the profile of reported adverse reactions and usually manifest in mild form and resolve after discontinuation of the drug or dose reduction.

Treatment. Symptomatic treatment should be considered as necessary. In individuals with normal kidney function, the drug is rapidly eliminated via the kidneys. Meropenem and its metabolites are removed from the body during hemodialysis.

Adverse reactions.

During the review of data from 4872 out of 5026 patients regarding the impact of meropenem treatment, the most common adverse reactions associated with the use of meropenem were diarrhea (2.3%), rash (1.4%), nausea/vomiting (1.4%), and injection site inflammation (1.1%). The most common laboratory test-related adverse reactions were thrombocytosis (1.6%) and elevated liver enzymes (1.5–4.3%). In Table 5, all adverse reactions are listed by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated based on available data).

Within each group, adverse reactions are listed in order of decreasing severity according to frequency.

Table 5

System organ class	Frequency	Adverse reaction
Infections and infestations	uncommon	Oropharyngeal and vaginal candidiasis.
Blood and lymphatic system disorders	common uncommon	Thrombocytosis. Eosinophilia, thrombocytopenia, leukopenia, neutropenia. Agranulocytosis, hemolytic anemia.
Immune system disorders	uncommon	Angioedema, anaphylactic reaction.
Nervous system disorders	common uncommon rare	Headache. Paresthesia. Seizures (see section "Special precautions").
Psychiatric disorders	rare	Delirium.
Gastrointestinal disorders	common uncommon	Diarrhea, vomiting, nausea, abdominal pain. Colitis associated with antibiotic use.
Hepatobiliary disorders	common uncommon	Elevated transaminase levels, elevated alkaline phosphatase levels in blood, elevated lactate dehydrogenase levels in blood. Elevated blood bilirubin levels.
Skin and subcutaneous tissue disorders	common uncommon frequency unknown	Rash, pruritus. Urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme. Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis.
Renal and urinary disorders	uncommon	Elevated serum creatinine levels, elevated blood urea levels.
General disorders and administration site conditions	common uncommon	Inflammation, pain. Thrombophlebitis. Injection site pain.

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

Reporting suspected adverse reactions.

Reporting of adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product to the State Expert Center of the Ministry of Health of Ukraine via the following link: https://aisf.dec.gov.ua/

Shelf life.

4 years.

3 years (for the 2000 mg dosage).

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C.

Store in the original packaging at a temperature not exceeding 25 °C (for the 2000 mg dosage). Keep out of reach of children.

Freshly prepared solutions of Meropenem-Vista for intravenous injection and infusion are recommended.

Each 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.

Unused product or waste material must be disposed of in accordance with local requirements.

Incompatibilities.

Meropenem-Vista should not be mixed or combined with other medicinal products. Meropenem-Vista 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.

500 mg or 1000 mg of powder in glass vials. 1 or 10 vials per cardboard box.

2000 mg of powder in a vial; 6 vials per cardboard box.

Prescription category.

Prescription only.

Manufacturer. ACS DOBFAR S.P.A.

Manufacturer's address and location of its business operations.

Nucleo Industriale S. Atto (loc. S. Nicola' A Tordino), 64100, Teramo (TE), Italy.