Merobac

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

Composition:

Active substance: meropenem;

1 vial contains 570 mg of meropenem trihydrate equivalent to 500 mg of anhydrous meropenem;

1 vial contains 1140 mg of meropenem trihydrate equivalent to 1000 mg of anhydrous meropenem;

Excipient: sodium carbonate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white to light yellow powder.

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

Pharmacological properties.

Pharmacodynamics.

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

Time above the minimum inhibitory concentration (T > MIC) demonstrated a high degree of correlation with efficacy. In preclinical models, meropenem demonstrated activity at plasma concentrations exceeding the MIC for microorganisms for approximately 40% of the dosing interval. This target value has not been established clinically.

Microbial resistance to meropenem.

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

In the European Union, outbreaks of infections 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, considering 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).

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

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
Non-species related breakpoints5	≤ 2	> 8

1. The susceptibility breakpoints for meropenem against 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 breakpoints 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 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), isolates should be reported as resistant.

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

4. The breakpoints apply only to meningitis.

5. Non-species-related 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-related breakpoints are based on the following dosing regimens: EUCAST breakpoints apply to meropenem administered at 1000 mg three times daily intravenously 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.

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

The prevalence of acquired resistance in individual species may vary geographically and over time; therefore, local data on microbial resistance should be consulted, especially when treating severe infections. When local resistance rates are 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 pathogenic microorganisms are listed 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 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 with potential for acquired resistance

Gram-positive aerobes

Enterococcus faecium^7,9

Gram-negative aerobes

Acinetobacter species

Burkholderia cepacia

Pseudomonas aeruginosa

Resistant microorganisms

Gram-negative aerobes

Stenotrophomonas maltophilia

Legionella species

Other microorganisms

Chlamydophila pneumoniae

Chlamydophila psittaci

Coxiella burnetii

Mycoplasma pneumoniae

7. Species exhibiting intrinsic 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 use data. Physicians should refer to national and/or international consensus guidelines for the treatment of glanders and melioidosis.

Pharmacokinetics

In healthy individuals, the mean plasma elimination half-life is approximately 1 hour; the mean volume of distribution is about 0.25 L/kg (11–27 L); the mean clearance is 287 mL/min after a 250 mg dose, decreasing to 205 mL/min after a 2 g dose. After administration of 500, 1000, and 2000 mg doses infused over 30 minutes, mean Cmax values were approximately 23, 49, and 115 µg/mL, respectively; corresponding AUC values were 39.3, 62.3, and 153 µg×h/mL. After 5-minute infusions, Cmax values were 52 and 112 µg/mL for 500 and 1000 mg doses, 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 receiving meropenem 1000 mg every 8 hours after surgery for intra-abdominal infections, Cmax and elimination half-life values were similar to those in healthy individuals, but the volume of distribution was higher (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 is 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 tissues, skin, fascia, muscle, and peritoneal exudates.

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, 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 the effect of probenecid indicate that meropenem undergoes both glomerular filtration and tubular secretion.

Renal impairment

Renal dysfunction results in higher plasma AUC values and a prolonged elimination half-life of meropenem. AUC increased 2.4-fold in patients with moderate renal impairment (creatinine clearance [CrCl] 33–74 mL/min), 5-fold in those with severe renal impairment (CrCl 4–23 mL/min), and 10-fold in patients on hemodialysis (CrCl < 2 mL/min), compared to healthy subjects (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 (see section "Dosage and administration").

Meropenem is removed by hemodialysis, with a clearance during dialysis 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 subjects 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 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 revealed a dose–half-life relationship similar to that in adults, except in the youngest patients (< 6 months: 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 plasma levels, although considerable inter-individual variability exists.

Pharmacokinetics of meropenem in neonates receiving antibacterial therapy showed higher clearance in neonates with greater chronological or gestational age, with a mean elimination half-life 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 healthy elderly subjects (65–80 years) showed reduced plasma clearance, correlating with age-related decline in creatinine clearance, and a slight reduction in non-renal clearance. Dose adjustment is not required in elderly patients unless moderate or severe renal impairment is present.

Clinical characteristics.

Indications.

Merobact 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.

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

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

Official recommendations regarding 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 interactions.

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

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

The potential effect of meropenem on protein binding in blood or metabolism of other drugs has not been studied. However, since protein binding is so low, such interactions with other compounds are unlikely.

Decreased levels of valproic acid in blood have been reported when co-administered with carbapenems, resulting in approximately 60–100% reduction in valproic acid levels within about 2 days. Due to the rapid onset and significant extent of the 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 potentiate its anticoagulant effect. Numerous reports have documented increased anticoagulant effect of oral anticoagulants, including warfarin, in patients receiving antibiotics concomitantly. The risk may vary depending on the type of underlying infection, age, and general condition of the patient, thus 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 immediately after concomitant use of antibiotics with oral anticoagulants.

Children

All drug interaction studies have been conducted only in adult patients.

Special precautions for use

When selecting meropenem as a treatment option, the following factors should be considered: severity of infection, prevalence of resistance to other appropriate antibacterial agents, and the risk of bacterial resistance to carbapenems.

Resistance in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter

In the European Union, resistance to penems among Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter varies. When prescribing the 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 during treatment with beta-lactam antibiotics (see sections "Contraindications" and "Adverse reactions").

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 careful patient history regarding previous hypersensitivity reactions to beta-lactam antibiotics should be obtained prior to initiating meropenem therapy.

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

Hypersensitivity reactions progressing to Kounis syndrome (acute allergic coronary artery spasm), which may lead to myocardial infarction, have been reported with other beta-lactam antibiotics (see section "Adverse reactions").

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. Therefore, this diagnosis should be considered in patients who develop diarrhea during or following treatment with meropenem (see section "Adverse reactions"). Discontinuation of meropenem therapy and initiation of specific treatment 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 "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 (see section "Adverse reactions").

Use in patients with hepatic disease: liver function should be closely monitored in patients with hepatic disease receiving meropenem. Dose adjustment is not required (see section "Method of administration and dosage").

Serum conversion in the direct antiglobulin test (Coombs test)

Treatment with meropenem 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").

Merobak contains approximately 2.0 mEq of sodium per 500 mg dose or 4.0 mEq per 1 g dose, which should be taken into account when prescribing to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

Pregnancy

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

Animal studies have not shown direct or indirect effects on reproductive toxicity. It is advisable to avoid the use of meropenem during pregnancy.

Breastfeeding

It has been reported that a small amount of meropenem passes into human breast milk. Meropenem may be used during lactation 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, caution is recommended due to the possibility of developing headache, paresthesia, or seizures, which have been reported during meropenem use.

Dosage and Administration.

Dosage

The following are general recommendations for dosing of the medicinal product.

The dose of meropenem and duration of treatment depend on the type of causative pathogen, severity of the infection, and the patient's response to therapy.

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

Special dosage recommendations must be followed when treating patients with renal impairment (see below).

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

Table 1

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
Treatment of febrile neutropenic patients	1 g

Merobact is usually administered as an intravenous infusion lasting from
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. Data supporting the safety of administering a 2 g dose as an intravenous bolus injection to adults are limited.

Renal impairment

Recommended doses for adults and children with body weight ≥50 kg
with creatinine clearance less than 51 ml/min

Table 2

Creatinine clearance (mL/min)	Single dose (see table 1)	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 doses of the medicinal product as indicated in Table 2, adjusted per 2 g dose unit, are limited.

Meropenem is removed by haemodialysis and haemofiltration; therefore, the required dose of the medicinal product should be administered after completion of the haemodialysis procedure.

There are no recommendations regarding the established dose of the medicinal product for patients undergoing peritoneal dialysis.

Hepatic impairment

Dose adjustment of the medicinal product is not required in patients with hepatic impairment (see section "Posology and method of administration").

Dosing in elderly patients

Dose 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

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").

Recommended doses for children aged 3 months to 11 years with body weight below 50 kg

Table 3

Infection	Single dose administered every 8 hours
Pneumonia, including community-acquired and hospital-acquired pneumonia	10 or 20 mg/kg body weight
Bronchopulmonary 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

Children with body weight of 50 kg

The dose should be used as for adult patients.

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

Route of administration

Merobact 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. Data supporting the safety of administering the drug at a dose of 40 mg/kg as an intravenous bolus injection in children are limited.

Administration of intravenous bolus injection

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

Chemical and physical stability of the prepared bolus injection solution is maintained for 3 hours at temperatures up to 25 °C or for 12 hours at 2–8 °C (in the refrigerator).

From a microbiological standpoint, if the method of opening/reconstitution/dilution does not exclude the risk of microbiological contamination, the medicinal product should be used immediately.

If the medicinal product is not used immediately, the physician is responsible for the duration and storage conditions after solution preparation.

Administration of intravenous infusion

The infusion solution should be prepared by dissolving the Merobact medicinal product 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 25 °C or for 24 hours at 2–8 °C (in the refrigerator). From a microbiological standpoint, the medicinal product should be used immediately. If the medicinal product is not used immediately, the physician is responsible for the duration and storage conditions.

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

Do not freeze prepared solutions.

Children

The medicinal product is indicated for use in children aged from 3 months.

Overdose

Relative overdose is possible in patients with impaired renal function if the dose of the drug is not adjusted as described in the section "Dosage and administration". Limited post-marketing experience indicates that if adverse reactions occur after overdose, they are consistent with the profile of adverse reactions (see section "Adverse reactions") and are generally mild 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.

Hemodialysis removes meropenem and its metabolites from the body.

Adverse reactions.

In clinical trials involving 4872 patients, the most commonly reported adverse reactions associated with meropenem administration were diarrhea (2.3%), rash (1.4%), nausea/vomiting (1.4%), injection site inflammation (1.1%), thrombocytosis (1.6%), and elevated liver enzymes (1.5–4.3%).

The adverse reactions listed below are categorized by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are listed in decreasing order of severity.

Infections and infestations. Uncommon: oral and vaginal candidiasis.

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

Immune system disorders. Uncommon: angioedema, anaphylactic reaction (see sections "Contraindications" and "Special warnings and precautions for use").

Nervous system disorders. Common: headache; uncommon: paresthesia; rare: seizures (see section "Special warnings and precautions for use").

Psychiatric disorders. Rare: delirium.

Gastrointestinal disorders. Common: diarrhea, vomiting, nausea, abdominal pain; uncommon: antibiotic-associated colitis (see section "Special warnings and precautions for use").

Hepatobiliary disorders. Common: increased levels of transaminases, increased alkaline phosphatase levels in blood, increased lactate dehydrogenase levels in blood; uncommon: increased bilirubin levels in blood.

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

Renal and urinary disorders. Uncommon: increased blood creatinine levels, increased blood urea levels.

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

Description of selected adverse reactions

Kounis syndrome

Cases of acute coronary syndrome associated with allergic reaction (Kounis syndrome) have been reported with other beta-lactam antibiotics (see section "Contraindications").

Pediatric population

Merobak is approved for use in children aged 3 months and older. 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 ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua/.

Shelf life. 4 years.

Each vial is for single use only.

Standard aseptic techniques should be used during solution preparation and administration.

The solution should be shaken before use.

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

Storage conditions.

Store at temperatures not exceeding 30 °C. Keep out of reach of children.

Incompatibilities. Merobak must not be mixed or combined with other medicinal products.

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

Merobak in vials intended 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.

Prescription status. Prescription only.

Manufacturer.

ACS DOBFAR S.P.A.

Manufacturer's address and location of operations.

NUCLEO INDUSTRIALE S. ATTO (LOC. S. NICOLÒ A TORDINO), 64100 TERAMO (TE), Italy.