Merogram

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT MEROGRAM (MEROGRAM)

Composition:

Active substance: meropenem;

1 vial contains a sterile mixture of meropenem trihydrate and sodium carbonate (equivalent to meropenem) – 500 mg or 1000 mg.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: white or almost white crystalline powder.

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 been shown to correlate 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 clinically established.

Bacterial resistance to meropenem may occur due to: (1) decreased permeability of the outer membrane of Gram-negative bacteria (due to reduced production of porins), (2) decreased 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 (EU), 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, with respect to relevant target microorganisms, is absent. 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 breakpoint values defined during clinical studies by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are listed 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
Species-unrelated breakpoint values5	≤ 2	> 8

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

2Strains with MIC values exceeding the S/R breakpoints are very rare or have not yet been reported. Testing for identification and antimicrobial susceptibility for any such isolate should be repeated, and if the result is confirmed, the isolate should be referred to a reference laboratory. Pending clinical outcome data for verified isolates with MIC values above the current resistance breakpoints (indicated in italics), isolates should be reported as resistant.

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

4Breakpoints apply only to meningitis.

5Non-species-related breakpoints have been defined primarily 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 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 intermediate/resistant breakpoints.

6Beta-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 may vary geographically and over time for individual species; therefore, local data on microbial resistance should be consulted, especially when treating severe infections. Where necessary, if local resistance prevalence is such that the benefit of using the medicinal product, at least for certain types of infections, is questionable, expert consultation should be sought.

Listed below are pathogenic microorganisms based on clinical experience and therapeutic treatment guidelines.

Commonly 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 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

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 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 individuals, the mean plasma elimination half-life (t½) 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. Following administration of 500, 1000, and 2000 mg doses infused over 30 minutes, mean peak plasma concentrations (Cmax index) were approximately 23, 49, and 115 µg/mL, respectively; corresponding AUC values were 39.3, 62.3, and 153 µg×h/mL.

Following a 5-minute infusion, Cmax index values were 52 and 112 µg/mL after 500 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 t½ values were similar to those observed in healthy volunteers, but with a larger volume of distribution (27 L).

Distribution

The mean plasma protein binding of meropenem is approximately 2% and is independent of drug concentration. Following rapid administration (5 minutes or less), 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 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 eliminated 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 prolonged t½ for 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 undergoing hemodialysis (CrCl <2 mL/min), compared to healthy subjects (CrCl >80 mL/min).

The 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 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 of the liver show 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 volume of distribution and clearance 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 observed in adults after 500, 1000, and 2000 mg doses, respectively.

Comparative studies revealed pharmacokinetic characteristics between doses and half-lives similar to those in adults, except in the youngest patients (<6 months, t½ 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 within 12 hours as meropenem and an additional 12% as metabolite. Cerebrospinal fluid meropenem concentrations in children with meningitis are approximately 20% of the simultaneously measured plasma concentration, although considerable inter-individual variability exists.

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

Geriatric 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 reduction in non-renal clearance. Dose adjustment is not required in elderly patients unless moderate or severe renal impairment is present.

Clinical characteristics.

Indications.

Merogram 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.

Merogram 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 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 interaction.

Studies on drug interaction with individual medicinal products, except probenecid, have not been conducted.

Probenecid competes with meropenem for active tubular secretion, thereby inhibiting renal excretion of meropenem, resulting in increased t1/2 and elevated plasma concentrations of meropenem. Caution should be exercised when probenecid is used concomitantly 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 via this mechanism are not expected.

Reduced serum levels of valproic acid have been reported when co-administered with carbapenems, with reductions of approximately 60–100% occurring within about two days. Due to the rapid onset and extent of this reduction, concomitant administration of valproic acid and carbapenems is considered uncorrectable; therefore, such interaction should be avoided (see section "Special precautions").

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 contribution of antibacterial agents to the increase in 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 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 carbapenem-resistant bacteria.

Resistance of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter

In the EU, 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

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

Patients with a history of hypersensitivity to carbapenems, penicillins, or other beta-lactam antibiotics may also have 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, administration of the drug must be discontinued immediately and appropriate measures should be initiated.

Antibiotic-associated colitis

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

Seizures

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

Liver function monitoring

Due to the risk of hepatotoxicity (liver function disturbances 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 closely 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)

Treatment with meropenem may result in a positive direct/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").

Merogram contains approximately 2.0 mEq or 4.0 mEq of sodium per 500 mg or 1 g dose, respectively, which should be taken into account when prescribing the medicinal product 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 number.

Animal studies have not shown direct or indirect effects of reproductive toxicity. Given the above, 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 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 medicinal product on the ability to drive vehicles or operate machinery have not been conducted.

When driving vehicles or operating machinery, caution should be exercised due to the possibility of developing headache, paraesthesia, or seizures, which have been reported during meropenem use.

Dosage and Administration.

The tables below (Tables 1–3) provide general recommendations for drug dosing. The dose of meropenem and duration of treatment depend on the causative pathogen, severity of the infection, and individual patient sensitivity.

Merogram, when administered at a dose of up to 2 g three times daily in adults and children with body weight over 50 kg, and up to 40 mg/kg three times daily in children, may be particularly 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 1

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	0.5 g or 1 g
Respiratory tract infections in cystic fibrosis	2 g
Complicated urinary tract infections	0.5 g or 1 g
Complicated intra-abdominal infections	0.5 g or 1 g
Infections during childbirth and postpartum infections	0.5 g or 1 g
Complicated skin and soft tissue infections	0.5 g or 1 g
Acute bacterial meningitis	2 g
Treatment of patients with febrile neutropenia	1 g

Merogram 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. Safety data supporting administration of a 2 g intravenous bolus dose to adults are limited.

Renal impairment

Table 2

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)	Dose (based on dosage units of 0.5 g, 1 g, 2 g)	Frequency
26-50	one dosage unit	every 12 hours
10-25	half a dosage unit	every 12 hours
<10	half a dosage unit	every 24 hours

Data supporting the use of the doses of the medicinal product indicated in Table 2, adjusted to a 2 g dose unit, 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 recommendations regarding the established dose of the medicinal product for patients receiving peritoneal dialysis.

Hepatic impairment

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

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. Limited pharmacokinetic data support the use of a meropenem dose of 20 mg/kg every 8 hours (see section "Pharmacokinetics").

Table 3

Recommended doses of the medicinal product 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

Children with body weight above 50 kg

The dose should be applied as for adult patients.

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

Method of administration

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

Preparation for intravenous bolus injection

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

Chemical and physical stability of the prepared bolus injection solution has been demonstrated for 3 hours at temperatures up to 25 °C or 12 hours under refrigerated conditions (2–8 °C).

From a microbiological point of view, 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 storage period and conditions of the prepared solution should be strictly controlled.

Preparation for intravenous infusion

The infusion solution should be prepared by dissolving the Merogram 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 has been demonstrated for 3 hours at 25 °C or for 24 hours under refrigerated conditions (2–8 °C).

From a microbiological point of view, the medicinal product should be used immediately. If the medicinal product is not used immediately, the storage period and conditions of the prepared solution should be strictly controlled.

The Merogram 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 3 months and older.

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". Limited post-marketing experience indicates that if adverse reactions occur following overdose, they are consistent with the profile of the specified adverse reactions and are usually mild in severity and resolve after discontinuation of the drug or dose reduction. Symptomatic treatment should be considered as necessary.

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

Hemodialysis removes meropenem and its metabolites from the body.

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.

Listed below are all adverse reactions 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 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 – paraesthesia; rare – seizures (see section "Special warnings and precautions for use").

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

Hepatobiliary disorders: common – increased transaminase levels, 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; frequency not known – drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

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.

There are no data suggesting an increased risk of adverse reactions 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 marketing authorization 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.

2 years.

Storage conditions.

Store out of reach of children at a temperature not exceeding 30°C.

After reconstitution, the product should be used immediately.

Incompatibilities.

Merogram must not be mixed or combined with other medicinal products.

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

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

Packaging.

1 vial of powder in a cardboard box.

Prescription category.

Prescription only.

Manufacturer.

Eugia Pharma Specialities Limited, Unit-2.

Manufacturer's address and place of business

A-1128, RIICO Industrial Area, Phase-III, Bhiwadi, Alwar District, Rajasthan, 301019, India.