INSTRUCTION

for medical use of the medicinal product

 

IFEEM

 

Composition:

active substance: meropenem;

1 vial contains: meropenem trihydrate equivalent to 1000 mg meropenem anhydrous;

excipients: sodium carbonate anhydrous.

 

Pharmaceutical form. Powder for solution for injection.

Basic physical and chemical properties: a colourless to white or pale yellow crystals or crystalline powder.

 

Pharmacotherapeutic group. Antibacterials for systemic use. Carbapenems. ATC code J01D H02.

 

Pharmacological properties.

Pharmacodynamics.

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

Similar to other beta-lactam antibacterial agents, the time that meropenem concentrations exceed the MIC (T>MIC) has been shown to best correlate with efficacy. In preclinical models meropenem demonstrated activity when plasma concentrations exceeded the MIC of the infecting organisms for approximately 40 % of the dosing interval. This target has not been established clinically.

Bacterial resistance to meropenem may result from: (1) decreased permeability of the outer membrane of Gram-negative bacteria (due to diminished production of porins) (2) reduced affinity of the target PBPs (3) increased expression of efflux pump components, and (4) production of beta-lactamases that can hydrolyse carbapenems.

Localised clusters of infections due to carbapenem-resistant bacteria have been reported in the European Union.

There is no target-based cross-resistance between meropenem and agents of the quinolone, aminoglycoside, macrolide and tetracycline classes. However, bacteria may exhibit resistance to more than one class of antibacterials agents when the mechanism involved includes impermeability and/or an efflux pump(s).

European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints for MIC testing are presented below.

 

Organism	Susceptible (S) (mg/l)	Resistant (R) (mg/l)
Enterobacteriaceae	≤ 2	> 8
Pseudomonas spp.	≤ 2	> 8
Acinetobacter spp.	≤ 2	> 8
Streptococcus groups A, B, C, G	note 6	note 6
Streptococcus pneumoniae1	≤ 2	> 2
Viridans group streptococci2	≤ 2	> 2
Enterococcus spp.	–	–
Staphylococcus spp.	note 3	note 3
Haemophilus influenzae1,2 and Моraxella 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 Meropenem breakpoints for Streptococcus pneumoniae and Haemophilus influenzae in meningitis are 0.25 mg/l (Susceptible) and 1 mg/l (Resistant).

² Isolates with MIC values above the susceptible breakpoint are very rare or not yet reported. The identification and antimicrobial susceptibility tests on any such isolate must be repeated and if the result is confirmed the isolate sent to a reference laboratory. Until there is evidence regarding clinical response for confirmed isolates with MIC values above the current resistant breakpoint they should be reported resistant.

³ Susceptibility of staphylococci to carbapenems is inferred from the cefoxitin susceptibility.

⁴ Breakpoints relate to meningitis only.

⁵ Non-species related breakpoints have been determined mainly from PK/PD data and are independent of the MIC distributions of specific species. They are for use only for organisms that do not have specific breakpoints. Non species related breakpoints are based on the following dosages: EUCAST breakpoints apply to meropenem 1000 mg x 3 daily administered intravenously over 30 minutes as the lowest dose. 2 g x 3 daily was taken into consideration for severe infections and for intermediate/resistant breakpoints.

⁶ The beta-lactam susceptibility of streptococcus groups A, B, C and G is inferred from the penicillin susceptibility.

«–» Susceptibility testing is not recommended because the species is a poor target for therapy with the drug. Isolates may be reported as resistant without prior testing.

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, the expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

The following table of pathogens listed is derived from clinical experience and therapeutic guidelines.

Commonly susceptible species

Gram-positive aerobes

Enterococcus faecalis⁷

Staphylococcus aureus (methicillin-susceptible)⁸

Staphylococcus spp. (methicillin-susceptible), including Staphylococcus epidermidis

Streptococcus agalactiae (Group В)

Streptococcus milleri group (S. anginosus, S. constellatus and S. intermedius)

Streptococcus pneumoniae

Streptococcus pyogenes (Group А)

Gram-negative aerobes

Citrobacter freundii

Citrobacter koseri

Enterobacter aerogenes

Enterobacter cloacae

Escherichia coli

Haemophilus influenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Morganella morganii

Neisseria meningitides

Proteus mirabilis

Proteus vulgaris

Serratia marcescens

Gram-positive anaerobes

Clostridium perfringens

Peptoniphilus asaccharolyticus

Peptostreptococcus spp. (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 Burkholderia cepacia spp.

Pseudomonas aeruginosa

Inherently resistant organisms

Gram-negative aerobes

Stenotrophomonas maltophilia

Legionella species

Other micro-organisms

Chlamydophila pneumoniae

Chlamydophila psittaci

Coxiella burnetii

Mycoplasma pneumoniae

⁷ Species that show 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: Use of meropenem in humans is based on in vitro B.mallei and B. pseudomallei susceptibility data and on limited human data. Treating physicians should refer to national and/or international consensus documents regarding the treatment of glanders and melioidosis.

Pharmacokinetics.

In healthy subjects the mean plasma half-life (t½) is approximately 1 hour; the mean volume of distribution is approximately 0.25 L/kg (11-27 L) and the mean clearance is 287 ml/min at 250 mg falling to 205 ml/min at 2 g. Doses of 500, 1000 and 2000 mg doses infused over 30 minutes give mean Cmax values of approximately 23, 49 and 115 μg/ml respectively, corresponding AUC values were 39.3, 62.3 and 153 μg.h/ml. After infusion over 5 minutes Cmax values are 52 and 112 μg/ml after 500 and 1000 mg doses respectively. When multiple doses are administered 8-hourly to subjects with normal renal function, accumulation of meropenem does not occur.

A study of 12 patients administered meropenem 1000 mg 8 hourly post-surgically for intra-abdominal infections showed a comparable C_max and t½ to normal subjects but a greater volume of distribution (27 L).

Distribution

The average plasma protein binding of meropenem was approximately 2 % and was independent of concentration. After rapid administration (5 minutes or less) the pharmacokinetics are biexponential but this is much less evident after 30 minutes infusion. Meropenem has been shown to penetrate well into several body fluids and tissues: including lung, bronchial secretions, bile, cerebrospinal fluid, gynaecological tissues, skin, fascia, muscle, and peritoneal exudates.

Biotransformation

Meropenem is metabolised by hydrolysis of the beta-lactam ring generating 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 requirement to co-administer a DHP-I inhibitor.

Elimination

Meropenem is primarily excreted unchanged by the kidneys; approximately 70 % (50 –75 %) of the dose is excreted unchanged within 12 hours. A further 28% is recovered as the microbiologically inactive metabolite. Faecal elimination represents only approximately 2% of the dose. The measured renal clearance and the effect of probenecid show that meropenem undergoes both filtration and tubular secretion.

Renal insufficiency

Renal impairment results in higher plasma AUC and longer half-life for meropenem. There were AUC increases of 2.4 fold in patients with moderate impairment (CrCL 33-74 ml/min), 5 fold in severe impairment (CrCL 4-23 ml/min) and 10 fold in haemodialysis patients (CrCL <2 ml/min) when compared to healthy subjects (CrCL >80 ml/min). The AUC of the microbiologically inactive ring opened metabolite was also considerably increased in patients with renal impairment. Dose adjustment is recommended for patients with moderate and severe renal impairment (see section "Method of administration and dosage").

Meropenem is cleared by haemodialysis with clearance during haemodialysis being approximately 4 times higher than in anuric patients.

Hepatic insufficiency

A study in patients with alcoholic cirrhosis shows no effect of liver disease on the pharmacokinetics of meropenem after repeated doses.

Adult patients

Pharmacokinetic studies performed in patients have not shown significant pharmacokinetic differences versus healthy subjects with equivalent renal function. A population model developed from data in 79 patients with intra-abdominal infection or pneumonia, has shown a dependence of the central volume on weight and the clearance on creatinine clearance and age.

Paediatric population

The pharmacokinetics in infants and children with infection at doses of 10, 20 and 40 mg/kg have shown C_max values approximating to those in adults following 500, 1000 and 2000 mg doses, respectively. Comparison has shown consistent pharmacokinetics between the doses and half-lives similar to those observed in adults in all but the youngest subjects (<6 months t_1/2 1.6 hours). The 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 over 12 hours as meropenem with a further 12 % as metabolite. Meropenem concentrations in the CSF of children with meningitis are approximately 20 % of concurrent plasma levels although there is significant inter- individual variability.

The pharmacokinetics of meropenem in neonates requiring anti-infective treatment has shown greater clearance in neonates with higher chronological or gestational age with an overall average half-life of 2.9 hours. Monte Carlo simulation based on a population PK model showed that a dose regimen of 20 mg/kg 8 hourly achieved 60 %T>MIC for P. aeruginosa in 95 % of pre-term and 91 % of full term neonates.

Elderly

Pharmacokinetic studies in healthy elderly subjects (65-80 years) have shown a reduction in plasma clearance, which correlated with age-associated reduction in creatinine clearance, and a smaller reduction in non-renal clearance. No dose adjustment is required in elderly patients, except in cases of moderate to severe renal impairment.

 

Clinical particulars.

Indications.

The medicinal product is indicated for the treatment of the following infections in adults and children over 3 months of age:

• pneumonia, including hospital and ventilator-associated pneumonia;
• bronchopulmonary infections in cystic fibrosis;
• complicated urinary tract infections;
• complicated intra-abdominal infections;
• intra- and post-partum infections;
• complicated skin and soft tissue infections;
• acute bacterial meningitis.

Meropenem may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection.

Treatment of patients with bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above.

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

 

Contraindications.

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

Hypersensitivity to any other carbapenem antibacterial agent.

Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of betalactam antibacterial agent (e.g. penicillins or cephalosporins).

 

Interaction with other medicinal products and other forms of interaction.

No specific medicinal product interaction studies other than probenecid have been performed.

Probenecid competes with meropenem for active tubular secretion and thus inhibits the renal excretion of meropenem with the effect of increasing the elimination half-life and plasma concentration of meropenem. Caution is required if probenecid is co-administered with meropenem.

The potential effect of meropenem on the protein binding of other medicinal products or metabolism has not been studied. However, the protein binding is so low that no interactions with other compounds would be expected on the basis of this mechanism.

Decreases in blood levels of valproic acid have been reported when it is co-administered with carbapenem agents resulting in a 60-100 % decrease in valproic acid levels in about two days. Due to the rapid onset and the extent of the decrease, co-administration of valproic acid/sodium valproate/valpromide with carbapenem agents is not considered to be manageable and therefore should be avoided (see section "Precautions for use").

Oral anti-coagulants

Simultaneous administration of antibiotics with warfarin may augment its anti-coagulant effects. There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of the antibiotic to the increase in INR (international normalized ratio) is difficult to assess. It is recommended that the INR should be monitored frequently during and shortly after co-administration of antibiotics with an oral anti-coagulant agent.

Paediatric population

Interaction studies have only been performed in adults.

 

Precautions for use.

The selection of meropenem to treat an individual patient should take into account the appropriateness of using a carbapenem antibacterial agent based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial agents and the risk of selecting for carbapenem-resistant bacteria.

Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp resistance

Resistance to penems of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp. varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in these bacteria to penems.

Hypersensitivity reactions

As with all beta-lactam antibiotics, serious and occasionally fatal hypersensitivity reactions have been reported (see sections "Contraindications" and "Adverse reactions").

Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may also be hypersensitive to meropenem. Before initiating therapy with meropenem, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics.

If a severe allergic reaction occurs, the medicinal product should be discontinued and appropriate measures taken.

Severe skin adverse reactions have been reported, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), multiform erythema, and acute generalized exantleptomatosis (see section "Adverse reactions"). If signs and symptoms of these reactions occur, meropenem should be immediately discontinued and alternative treatment considered.

Antibiotic-associated colitis

Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all anti- bacterial agents, including meropenem, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of meropenem (see section "Adverse reactions"). Discontinuation of therapy with meropenem and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.

Seizures

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

Hepatic function monitoring

Hepatic function should be closely monitored during treatment with meropenem due to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytolysis) (see section "Adverse reactions").

Use in patients with liver disease: patients with pre-existing liver disorders should have liver function monitored during treatment with meropenem. No dose adjustment is required (see section "Method of administration and dosage").

Direct antiglobulin test (Coombs test) seroconversion

A positive direct or indirect Coombs test may develop during treatment with meropenem.

Concomitant use with valproic acid/sodium valproate/valpromide

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

This medicinal product contains 90.2 mg sodium per dose. This should be particularly taken into account for patients on a low salt diet.

 

Pregnancy and lactation.

Pregnancy

There are no or limited amount of data from the use of meropenem in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of meropenem during pregnancy.

Breastfeeding

Small amounts of meropenem have been reported to be excreted in human milk. Meropenem should not be used in breast-feeding women unless the potential benefit for the mother outweighs the potential risk to the baby.

 

Effects on ability to drive and use machines.

No studies on the effect on the ability to drive and use machines have been performed. However, when driving or operating machines, it should be taken into account that headache, paraesthesia and convulsions have been reported for meropenem.

 

Method of administration and dosage.

Dosage

The tables below provide general recommendations for dosing.

The dose of meropenem administered and the duration of treatment should take into account the type of infection to be treated, including its severity, and the clinical response.

Meropenem, when used at a dose of up to 2 g three times a day in adults and children weighing more than 50 kg and at a dose of up to 40 mg/kg three times a day in children, may be particularly appropriate when treating some types of infections, such as infections due to less susceptible bacterial species (e.g. Enterobacteriaceae Pseudomonas aeruginosa or Acinetobacter spp.) or very severe infections.

Additional considerations for dosing are needed when treating patients with renal insufficiency (see further below).

Table 1

Recommended doses for adults and children weighing more than 50 kg

Infection	Dose to be administered every 8 hours
Pneumonia including hospital and ventilator-associated pneumonia.	500 mg or 1 g
Bronchopulmonary infections in cystic fibrosis	2 g
Complicated urinary tract infections	500 mg or 1 g
Complicated intra-abdominal infections	500 mg or 1 g
Intra- and post-partum infections	500 mg or 1 g
Complicated skin and soft tissue infections	500 mg or 1 g
Acute bacterial meningitis	2 g
Management of febrile neutropenic patients	1 g

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

Alternatively, doses up to 1 g can be given as an intravenous bolus injection over approximately 5 minutes. There are limited safety data available to support the administration of a 2 g dose in adults as an intravenous bolus injection.

Renal impairment

Table  2

Recommended doses for adults and children weighing more than 50 kg if creatinine clearance is less than 51 ml/min in such patients

Creatinine clearance (ml/min)	Dose (see Table 1)	Frequency
26‒50	one unit dose	every 12 hours
10‒25	half of one unit dose	every 12 hours
<10	half of one unit dose	every 24 hours

There are limited data to support the administration of these dose adjustments for a unit dose of 2 g.

Meropenem is cleared by haemodialysis and hemofiltration. The required dose should be administered after completion of the haemodialysis cycle.

There are no established dose recommendations for patients receiving peritoneal dialysis.

Hepatic impairment

No dose adjustment is required for patients with hepatic impairment (see section "Precautions for use").

Dose in elderly patients

No dose adjustment is required for elderly with normal renal function or creatinine clearance values above 50 ml/min.

Children under 3 months of age

The safety and efficacy of meropenem in children under 3 months of age have not been established and the optimal dose regimen has not been identified. However, limited pharmacokinetic data suggest that 20 mg/kg every 8 hours may be an appropriate regimen (see section “Pharmacokinetics”).

Table  3

Recommended doses for children from 3 months to 11 years of age and up to 50 kg body weight

Infection	Dose to be administered every 8 hours
Pneumonia including hospital and ventilator-associated 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
Management of febrile neutropenic patients	20 mg/kg body weight

 

Children over 50 kg body weight

The adult dose should be administered.

There is no experience in children with renal impairment.

Method of administration

Meropenem is usually given by intravenous infusion over approximately 15 to 30 minutes. Alternatively, meropenem doses of up to 20 mg/kg may be given as an intravenous bolus over approximately 5 minutes. There are limited safety data available to support the administration of a 40 mg/kg dose in children as an intravenous bolus injection.

Intravenous bolus injection administration

A solution for bolus injection is prepared by dissolving the drug product meropenem in sterile water for injection to a final concentration of 50 mg/ml.

Chemical and physical in-use stability for a prepared solution for bolus injection has been demonstrated for 3 hours at a temperature not exceeding 25 °C or 12 hours under refrigerated conditions (2-8 °C).

From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbiological contamination, the product should be used immediately.

If not immediately used, the shelf life and storage conditions of the reconstituted solution must be carefully monitored.

Intravenous infusion administration

A solution for infusion is prepared by dissolving the drug product meropenem in either 0.9% sodium chloride solution for infusion or 5% glucose (dextrose) solution for infusion to a final concentration of 1 to 20 mg/ml.

Chemical and physical in-use stability for a prepared solution for infusion using 0.9% sodium chloride solution has been demonstrated for 3 hours at a temperature 25 °C or 24 hours under refrigerated conditions (2-8 °C). From a microbiological point of view, the medicinal product should be used immediately. If not immediately used, the shelf life and storage conditions of the reconstituted solution must be carefully monitored.

Reconstituted solution of meropenem in 5% glucose (dextrose) solution should be used immediately.

Do not freeze the reconstituted solution.

 

Children.

Meropenem is licensed for children over 3 months of age.

 

Overdose.

Relative overdose may be possible in patients with renal impairment if the dose is not adjusted as described in section "Method of administration and dosage". Limited post-marketing experience indicates that if adverse reactions occur following overdose, they are consistent with the adverse reaction profile described in section "Adverse reactions", are generally mild in severity and resolve on withdrawal or dose reduction. Symptomatic treatments should be considered.

In individuals with normal renal function, rapid renal elimination will occur.

Haemodialysis will remove meropenem and its metabolite.

 

Adverse reactions.

In a review of 4,872 patients with 5,026 meropenem treatment exposures, meropenem-related adverse reactions most frequently reported were diarrhoea (2.3 %), rash (1.4 %), nausea/vomiting (1.4 %) and injection site inflammation (1.1 %). The most commonly reported meropenem-related laboratory adverse events were thrombocytosis (1.6 %) and increased hepatic enzymes (1.5-4.3 %).

In the table below all adverse reactions are listed 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) and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Infections and infestations: uncommon – oral and vaginal candidiasis.

Blood and lymphatic system disorders: common – thrombocythaemia; uncommon – eosinophilia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, haemolytic anaemia.

Immune system disorders: uncommon – angioedema, anaphylaxis (see sections "Contraindications" and "Precautions for use").

Nervous system disorders: common – headache; uncommon – paraesthesiae; rare – convulsions (see section "Precautions for use").

Gastrointestinal disorders: common – diarrhoea, vomiting, nausea, abdominal pain; uncommon – antibiotic-associated colitis (see section "Precautions for use").

Hepatobiliary disorders: common – transaminases increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased; uncommon – blood bilirubin increased.

Skin and subcutaneous tissue disorders: common – rash, pruritis; uncommon – urticaria, toxic epidermal necrolysis, Stevens Johnson syndrome, erythema multiform (see section "Precautions for use"); not known – Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS-syndrome), acute generalized exanthematous pustulosis (see section "Precautions for use").

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

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

There is no evidence of an increased risk of any adverse drug reaction in children based on the limited available data. All reports received were consistent with events observed in the adult population.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after the registration of a medicinal product is of great importance. It enables the monitoring of the benefit/risk ratio associated with the use of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions under legislation.

 

Shelf life. 2 years.

 

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children.

Do not freeze.

Each vial is for single use only.

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

The solution should be shaken before use.

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

 

Incompatibility.

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

Meropenem intended for bolus intravenous injection, must be reconstituted in sterile water for injection.

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

 

Packaging. Powder is in a glass vial, sealed with a rubber stopper and an aluminium cap with a flip-off component. One vial in a box.

 

Terms of dispensing. On prescription.

 

Date of last update.

04.02.2023