Meroneme synonyms. Meronem: instructions for use. Cross-drug interactions

Dosage form: powder for preparing a solution for intravenous administration

Compound
One bottle contains:

Meronem® 0.5 g Meronem® 1 g
Active Ingredient:
meropenem trihydrate 570 mg 1140 mg
equivalent to anhydrous meropenem 500 mg 1000 mg
Auxiliary ingredient:
sodium carbonate (anhydrous) 104 mg 208 mg

Description
Powder from white to light yellow.

Pharmacotherapeutic group
Antibiotic, carbapenem

ATX code: J01DH02

Pharmacological properties
Pharmacodynamics
Meropenem is an antibiotic of the carbapenem class, intended for parenteral use, relatively resistant to human dehydropeptidase-1 (DHP-1), and does not require additional administration of a DHP-1 inhibitor.
Meropenem has a bactericidal effect due to its effect on the synthesis of the bacterial cell wall. High bactericidal activity of meropenem against wide range aerobic and anaerobic bacteria due to the high ability of meropenem to penetrate the cell wall of bacteria, high level stability to most b-lactamases and significant affinity to various penicillin-binding proteins (PBPs). Minimum bactericidal concentrations (MBCs) are usually the same as minimum inhibitory concentrations (MICs). For 76% of the bacterial species tested, the MBC/MIC ratio was 2 or less.
In vitro tests show that meropenem acts synergistically with various antibiotics. In vitro and in vivo tests have shown that meropenem has a post-antibiotic effect.
Microorganisms may have one or more of the following mechanisms of resistance to meropenem: impaired permeability of the cell wall of gram-negative bacteria due to impaired porin synthesis; decreased affinity for target PBPs; activation of efflux mechanisms; production of beta-lactamases, under the influence of which hydrolysis of carbapenems occurs.
The only recommended criteria for sensitivity to meropenem are based on the pharmacokinetics of the drug and on the correlation of clinical and microbiological data - zone diameter and MIC determined for the relevant pathogens.
The sensitivity threshold for Streptococcus pneumoniae and Haemophilus influenzae for meningitis is 0.25 mg/l.
Strains for which the MIC is above the sensitivity threshold are rare or not currently detected. If such a strain is detected, the MIC test is repeated; when the result is confirmed, the strain is sent to a reference laboratory, and the strain is considered resistant until a confirmed result is received. clinical effect regarding him.
Values ​​used for meningitis only.
For all other pathogens, according to pharmacokinetic and pharmacodynamic data, without taking into account the specific distribution of MICs of specific pathogens.
Susceptibility testing is not recommended because this pathogen is not an optimal target for meropenem.
Susceptibility to meropenem should be determined using standard methods. Interpretation of results should be done in accordance with local guidelines.
The effectiveness of the drug against the pathogens listed below is confirmed by experience clinical application and guidelines for antibacterial therapy:
Pathogens sensitive to meropenem:
Gram-positive aerobes:
Enterococcus faecalis1
Staphylococcus aureus (methicillin-sensitive)2
Genus Staphylococcus (methicillin-sensitive), including Staphylococcus epidermidis
Streptococcus agalactiae group B
Streptococcus milleri group (S. anginosus, S. constellatus, 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
Genus Peptostreptococcus (including P. micros, P anaerobius, P. magnus)
Gram-negative anaerobes:
Bacteroides caccae
Bacteroides fragilis
Prevotella bivia
Prevotella disiens
Pathogens for which the problem of acquired resistance is relevant:
Gram-positive aerobes:
Enterococcus faecium1
Gram-negative aerobes:
Genus Acinetobacter
Burkholderia cepacia
Pseudomonas aeruginosa
Pathogens with natural resistance:
Gram-negative aerobes:
Stenotrophomonas maltophilia
Legionella spp.
Other pathogens:
Chlamydophila pneumoniae
Chlamydophila psittaci
Coxiella burnetii
Mycoplasma pneumoniae
Pathogens with intermediate sensitivity.
All methicillin-resistant staphylococci are resistant to meropenem.

Pharmacokinetics
Intravenous administration of Meronem® over 30 minutes to healthy volunteers results in maximum plasma concentrations of approximately 11 mcg/ml for a 250 mg dose, 23 mcg/ml for a 500 mg dose and 49 mcg/ml for a 1 g dose.
However, for maximum concentration (Cmax) and area under the concentration-time pharmacokinetic curve (AUC), there is no absolute pharmacokinetic proportional dependence from the administered dose. There was a decrease in plasma clearance from 287 to 205 ml/min for doses from 250 mg to 2 g.
Intravenous bolus injection of Meronem® into healthy volunteers over 5 minutes results in maximum plasma concentrations of approximately 52 mcg/mL for a 500 mg dose and 112 mcg/mL for a 1 g dose.
6 hours after intravenous administration of 500 mg, the concentration of meropenem in the blood plasma decreases to values ​​of 1 mcg/ml and below.
Extended (up to 3 hours) infusion of carbapenems can lead to optimization of their pharmacokinetic and pharmacodynamic parameters. With a standard 30-minute infusion in healthy volunteers of two doses of 500 and 2000 mg every 8 hours, the %T>MIC value (the ratio between the period of time when the drug concentration exceeds the MIC and the dosing interval; MIC = 4 μg/ml) was 30%, respectively. and 58%. When the same doses were administered to volunteers by 3-hour infusion every 8 hours, the %T>MIC increased to 43 and 73%, for 500 and 2000 mg, respectively. The mean plasma concentration in healthy volunteers following a 10-minute intravenous bolus of 1000 mg exceeded the MIC of 4 μg/mL for 42% of the dosing interval compared with 59% for a 3-hour infusion of 1000 mg.
Meropenem penetrates well into most body tissues and fluids, including the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations greater than those required to inhibit most bacteria.
With repeated administration of meropenem at intervals of 8 hours to patients with normal renal function, no accumulation of the drug is observed. In patients with normal renal function, the half-life is approximately 1 hour.
Plasma protein binding is approximately 2%.
About 70% of an intravenous dose of Meronem® is excreted unchanged by the kidneys within 12 hours, after which negligible renal excretion is determined. Urinary meropenem concentrations greater than 10 mcg/mL are maintained for 5 hours after a 500 mg dose. With dosing regimens of 500 mg every 8 hours or 1 g every 6 hours, no accumulation of meropenem in plasma or urine was observed in volunteers with normal liver function.
The only metabolite of meropenem is microbiologically inactive.
Studies in children have shown that the pharmacokinetics of Meronem® in children and adults is similar. The half-life of meropenem in children under 2 years of age is approximately 1.5-2.3 hours, with a linear relationship observed in the dose range of 10-40 mg/kg.
Kidney failure
Pharmacokinetic studies in patients with renal failure showed that meropenem clearance correlates with creatinine clearance. In such patients, dose adjustment is necessary.
A pharmacokinetic study in elderly subjects revealed a decrease in meropenem clearance, which correlated with age-related decline creatinine clearance.
Meropenem is eliminated by hemodialysis with a clearance approximately 4 times higher than the clearance of meropenem in anuric patients.
Liver failure
Pharmacokinetic studies in patients with liver disease showed that the data pathological changes do not affect the pharmacokinetics of meropenem.

Indications for use
Meronem® is indicated for the treatment in children (over 3 months) and adults of the following infectious and inflammatory diseases caused by one or more pathogens sensitive to meropenem:
- pneumonia, including nosocomial pneumonia;
- infections of the urinary system;
- abdominal infections;
- infectious and inflammatory diseases of the pelvic organs, such as endometritis;
- infections of the skin and its structures;
- meningitis;
- septicemia.
Empirical treatment of adult patients with suspected infection and symptoms of febrile neutropenia, either alone or in combination with antiviral or antifungal drugs.
The effectiveness of Meronem® has been proven both in monotherapy and in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Contraindications
History of hypersensitivity to meropenem or other drugs of the carbapenem group.
Severe hypersensitivity (anaphylactic reactions, severe skin reactions) to any antibacterial agent having a beta-lactam structure (i.e. penicillins or cephalosporins).
Children under 3 months.

Carefully
Concomitant use with potentially nephrotoxic drugs.
Patients with complaints from gastrointestinal tract(diarrhea), especially for those suffering from colitis.

Use during pregnancy and during breastfeeding
Pregnancy
The safety of Meronem® in women during pregnancy has not been studied. Animal studies have not shown any adverse effects on the developing fetus.
Meronem® should not be used during pregnancy unless the potential benefit to the mother outweighs the possible risk to the fetus. In each case, the drug must be used under the strict supervision of a physician.
Breastfeeding period
Data have been obtained on the excretion of meropenem in breast milk. Meronem® should not be used during breastfeeding, unless the potential benefit to the mother from using the drug outweighs the possible risk to the baby. Having assessed the benefit for the mother, a decision should be made to stop breastfeeding or to discontinue the drug Meronem®.

Directions for use and doses
Adults
The dose and duration of therapy should be based on the type and severity of the infection and the patient's condition.
The following daily doses are recommended:
500 mg IV every 8 hours for the treatment of pneumonia, infections urinary tract, gynecological infections such as endometritis, infections of the skin and skin structures;
1 g intravenously every 8 hours for the treatment of nosocomial pneumonia, peritonitis, suspected bacterial infection in patients with symptoms of neutropenia as well as septicemia.
For the treatment of meningitis, the recommended dose is 2 g every 8 hours.
For the treatment of certain infections, particularly those caused by less sensitive pathogens (such as Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.), or for very severe infections, the recommended dose is up to 2 g every 8 hours.
The safety of the 2 g dose as a bolus injection has not been sufficiently studied.
Dose in adult patients with impaired renal function
In patients with creatinine clearance less than 51 ml/min, the dose should be reduced as follows:

Creatinine clearance (ml/min) - Dose (based on 500 mg, 1 g, 2 g dose unit) - Frequency of administration
26-50 one dose unit every 12 hours
10-25 0.5 dose units every 12 hours
< 10 0,5 единицы дозы каждые 24 часа

Meropenem is eliminated by hemodialysis and hemofiltration. If long-term treatment with Meronem® is required, it is recommended that the drug (depending on the type and severity of infection) be administered at the end of the hemodialysis procedure to restore effective plasma concentrations.
There are currently no data on experience with the use of Meronem® for administration to patients undergoing peritoneal dialysis.
Dosing in Adult Patients with Hepatic Impairment
In patients with liver failure there is no need for dose adjustment (see section "Special Instructions").
Elderly patients
In elderly patients with normal renal function or creatinine clearance more than 50 ml/min, no dose adjustment is required.
Children
For children aged 3 months to 12 years, the recommended intravenous dose is 10-20 mg/kg every 8 hours depending on the type and severity of infection, the sensitivity of the pathogen and the patient's condition.
In children weighing more than 50 kg, adult doses should be used.
For meningitis, the recommended dose is 40 mg/kg every 8 hours.
For the treatment of certain infections, particularly those caused by less sensitive pathogens (such as Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.), or for very severe infections, the recommended dose is up to 40 mg/kg every 8 hours.
The safety of the 40 mg/kg bolus dose has not been sufficiently studied.
There is no experience in using the drug in children with impaired liver and kidney function.
Method of administration
Meronem® for intravenous use can be administered as an intravenous bolus injection over at least 5 minutes, or as an intravenous infusion over 15-30 minutes; Appropriate infusion fluids should be used for dilution.
The possibility of using meropenem in an extended infusion mode (up to 3 hours) is based on pharmacokinetic and pharmacodynamic parameters (see section “Pharmacokinetics”). To date, clinical and safety data supporting this regimen are limited.
To prepare a solution for intravenous bolus injections, Meronem® should be dissolved sterile water for injection (5 ml per 250 mg of meropenem), with the solution concentration being 50 mg/ml. The resulting solution remains stable for 3 hours at temperatures up to 25°C and for 16 hours when stored in the refrigerator (2-8°C).
To prepare a solution for intravenous infusions Meronem® should be dissolved in 0.9% sodium chloride solution for infusion or 5% dextrose (glucose) solution for infusion, and the concentration of the solution should be from 1 to 20 mg/ml. The resulting solution remains stable for 3 hours at temperatures up to 25°C and for 24 hours when stored in a refrigerator (2-8°C), if a 0.9% sodium chloride solution was used for its preparation. The solution prepared using 5% glucose solution should be used immediately.
The Meronem® solution should not be frozen.
It is recommended to administer the prepared solution immediately after preparation (from a microbiological point of view), if the conditions for preparing the solution do not exclude the possibility of microbiological contamination.

Side effect
In general, meropenem is well tolerated. In rare cases side effects led to discontinuation of therapy. Serious adverse reactions are rare.
Frequency adverse reactions is given in the table in the form of the following gradation: very often (≥1/10); often (≥1/100,<1/10); нечасто (≥1/1000, <1/100); редко (≥1/10000, <1/1000); очень редко (<1/10000); неуточненной частоты (частота не может быть определена на основании имеющихся данных).
Organs and systems
Side effects
Hematopoietic system*
Common: thrombocytosis
Uncommon: eosinophilia, thrombocytopenia
Rare: leukopenia, neutropenia, agranulocytosis
Very rare: hemolytic anemia
Nervous system
Uncommon: headache, paresthesia, syncope**, hallucinations**, depression**, anxiety**, irritability**, insomnia**
Rarely: seizures
Gastrointestinal tract
Often: nausea, vomiting, diarrhea, increased activity of liver transaminases, alkaline phosphatase, lactate dehydrogenase and bilirubin concentration in the blood serum
Uncommon: constipation**, cholestatic hepatitis**
Very rare: pseudomembranous colitis
Skin and subcutaneous tissue
Uncommon: rash, urticaria, pruritus
Very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Unspecified frequency: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
The immune system
Very rare: angioedema, manifestations of anaphylaxis
The cardiovascular system
Uncommon: heart failure**, cardiac arrest**, tachycardia**, bradycardia**, myocardial infarction**, decreased or increased blood pressure (BP)**, thromboembolism of pulmonary artery branches**
Kidneys and urinary tract
Uncommon: increased blood creatinine concentration, increased blood urea concentration
Respiratory tract
Uncommon: dyspnea**
Others
Often: local reactions - inflammation, thrombophlebitis, pain at the injection site
Rare: vaginal candidiasis and candidiasis of the oral mucosa
*Cases of a positive direct or indirect Coombs test, as well as cases of decreased partial thromboplastin time, have been reported.
**A cause-and-effect relationship with taking Meronem® has not been established. Adverse effects were observed in a study of 2904 immunocompetent adult patients treated with Meronem (500 mg or 1000 mg every 8 hours) due to non-CNS infections. In 36 patients, therapy was discontinued due to adverse events. In 5 cases, a connection between the death and the therapy cannot be ruled out. Given the serious condition of the patients, numerous diseases and multiple concomitant therapy with other drugs, it was not possible to draw a conclusion about the connection of the side effect with therapy with Meronem®.

Overdose
Accidental overdose during treatment is possible, especially in patients with impaired renal function.
Treatment in case of overdose should be symptomatic. Normally, the drug is rapidly eliminated through the kidneys. In patients with impaired renal function, hemodialysis effectively removes meropenem and its metabolite.

Interaction with other drugs
Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and plasma concentration of meropenem. Since the efficacy and duration of action of Meronem® administered without probenecid are adequate, coadministration of probenecid with Meronem® is not recommended.
The possible effect of Meronem® on the degree of binding of other drugs to plasma proteins or metabolism has not been studied. The binding of Meronem® to plasma proteins is low (about 2%), therefore, interaction with other drugs based on the mechanism of displacement from plasma proteins is not expected.
Co-administration of carbapenems and valproic acid preparations led to a decrease in the concentration of valproic acid in the blood plasma by 60-100% after 2 days of therapy. Due to the rapid and significant decrease in the concentration of valproic acid, co-administration of Meronem® and valproic acid preparations is not recommended.
The use of Meronem® while taking other drugs was not accompanied by the development of adverse pharmacological interactions. Studies examining the interaction of meropenem with other drugs (except probenecid) have not been conducted.
Cases of increased anticoagulant effect have been repeatedly reported when indirect anticoagulants (for example, warfarin) and antibacterial drugs are taken together. The risk of increased anticoagulant effect may depend on the nature of the infection, age and general condition of the patient, so it is difficult to assess the effect of an antibacterial drug on increasing the international normalized ratio (INR).
Frequent INR monitoring is recommended during co-administration of an antibacterial drug and an indirect anticoagulant and for some time after its cessation.

special instructions
There is no experience with the use of the drug in pediatric practice in patients with neutropenia or with primary or secondary immunodeficiency.
As with other antibiotics, regular susceptibility testing is recommended when meropenem is used as monotherapy in critically ill patients with known or suspected lower respiratory tract infection caused by Pseudomonas aeruginosa.
In rare cases, when using the drug Meronem®, as with the use of almost all antibiotics, the development of pseudomembranous colitis is observed, which can vary in severity from mild to life-threatening forms. It is important to remember the possibility of developing pseudomembranous colitis if diarrhea occurs while using the drug Meronem®. If pseudomembranous colitis develops, Meronem® should be discontinued. The use of drugs that inhibit intestinal motility is contraindicated.
Convulsions have been reported infrequently with the use of carbapenems, including meropenem. Caution should be exercised when using Meronem® in patients with a reduced seizure threshold.
There are clinical and laboratory signs of cross-allergic reactions between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. There are rare reports of cases of hypersensitivity reactions (including fatal ones) when using the drug Meronem®, as well as other beta-lactam antibiotics (see section “Side effects”). Before initiating meropenem therapy, the patient should be carefully interviewed, paying particular attention to any history of hypersensitivity reactions to beta-lactam antibiotics. Meronem should be used with caution in patients with a history of hypersensitivity reactions to beta-lactam antibiotics (i.e. penicillins and cephalosporins). If an allergic reaction to meropenem occurs, it is necessary to stop administering the drug and take appropriate measures.
The use of Meronem® in patients with liver disease should be carried out under careful monitoring of transaminase activity and bilirubin concentration.
As with other antibiotics, overgrowth of non-susceptible microorganisms is possible, and therefore constant monitoring of the patient is necessary.
The prevalence of acquired antibiotic resistance of various pathogens may vary depending on the region and over time, and it is desirable to have up-to-date information on the resistance of common pathogens in a particular region, especially when treating severe infections. If resistance is such that the effectiveness of the drug against at least some infections becomes doubtful, an expert should be consulted.
Co-administration of Meronem® and valproic acid preparations is not recommended due to a possible decrease in the concentration of valproic acid in the blood serum. In some patients, subtherapeutic concentrations may be achieved (see section "Interaction with other drugs").
The use of the drug for infections caused by methicillin-resistant staphylococcus is not recommended.

Impact on the ability to drive a car and operate equipment
There have been no studies of the effect of Meronem® on the ability to drive a car or use other equipment. However, it should be taken into account that headache, paresthesia and convulsions may occur when taking Meronem®.

Release form
Powder for the preparation of solution for intravenous administration, 0.5 g and 1 g.
0.5 g of active substance in glass bottles with a capacity of 10 ml and 20 ml and 1 g of active substance in glass bottles with a capacity of 30 ml (type 1 Eur.Pharm.) closed with a rubber stopper, crimped with an aluminum ring and a plastic cap. The AZ logo is painted on the outer surface of the bottle. 10 bottles with instructions for use in a cardboard box with first opening control.

Storage conditions
Store at a temperature not exceeding 30 C. Keep out of the reach of children.

Best before date
4 years. Do not use after the expiration date stated on the packaging.

Conditions for dispensing from pharmacies
On prescription.

Name and address of the legal entity in whose name the registration certificate was issued
AstraZeneca UK Limited, 2 Kingdom Street, London W2 6BD, UK
AstraZeneca UK Limited, 2 Kingdom Street, London W2 6BD, United Kingdom

Manufacturer
Dainippon Sumitomo Pharmaceuticals Company Co.,Ltd.
Tsurusaki 2200, Oita City, Oita, 870-0106, Japan
Dainippon Sumitomo Pharmaceuticals Company Ltd,
Tsurusaki 2200, Oita City, Oita, 870-0106, Japan
2. ACS Dobfar SpA, Viale Addetta 4/12, Tribiano, Milan, 20067, Italy
ACS Dobfar Spa, Viale Addetta 4/12, Tribiano, Milan, 20067, Italy

Issue quality control
AstraZeneca UK Limited, Silk Road Business Park, Macclesfield, Cheshire SK 10 2NA, UK
AstraZeneca UK Limited, Silk Road Business Park Macclesfield Cheshire SK 10 2NA, United Kingdom

Meronem is a medicine belonging to the group of antibiotics. It effectively copes with harmful bacteria of aerobic and anaerobic nature. The active substance of this drug penetrates the cells of microorganisms and blocks their synthesis. The result is complete elimination of the infection. This medicine should only be used after consulting a doctor. Otherwise, there is a high probability of harm to health.

Composition and release form

The main indicator of the admissibility of taking a drug is its presence in the register of medicines (RLS). Meronem can be purchased in pharmacies in any city. To do this, you will need not only a large amount, but also a doctor’s prescription. Without it, you will not be able to legally buy medicine.

The price of the antibiotic Meronem (INN Meropenem) directly depends on the amount of the active substance contained in the drug. It is produced in glass bottles with a capacity of 10, 20 or 30 milliliters. They are tightly closed with a rubber stopper and crimped with an aluminum ring. There is a plastic cover on top. Bottles are packed in cardboard boxes of 10 pieces.

Meronem consists of the following components:

1. Meropenem trihydrate. This chemical compound acts as an active substance. In one bottle its content ranges from 570 to 1140 mg (corresponding to 500 mg of anhydrous meropenem). The volume depends on the size of the container and the concentration of the drug.
2. Anhydrous sodium carbonate. It is added to Meronem as an excipient. Its amount can vary from 104 to 208 mg.

The medicine is available only in powder form, which may be white or light yellow. The prepared drug is packaged in bottles of 0.5 or 1 gram. This powder is intended for self-preparation of a solution that is administered intravenously.

Indications for use

This medicine can be used for both adults and children. The only difference in application will be the dosages.

This drug is prescribed for the following diseases and conditions:

• pneumonia and any other respiratory problems;
• inflammation in the pelvis;
• endometritis;
• diseases of the genitourinary system;
• gynecological complications after childbirth;
• bacterial meningitis;
• peritonitis, appendicitis and other inflammations in the abdominal cavity;
• blood poisoning;
• various infectious diseases of the skin and soft tissues (impetigo, erysipelas, dermatosis);
• neuropenia (decrease in the number of neutrophils in the blood).

Contraindications

Meronem, like any other drug, has several contraindications. They must be taken into account before taking, since carelessness can lead to an exacerbation of the disease, as well as a severe deterioration in health.

It is prohibited to use the medicine in the following cases:

• individual intolerance to the active substance (meropenem trihydrate);
• hypersensitivity to sodium carbonate;
• During pregnancy and breastfeeding;
• anaphylactic reactions to certain antibiotics (cephalosporin, penicillin);
• infants up to 3 months;
• simultaneously with nephrotoxic antibiotics;
• colitis, diarrhea and other problems with the gastrointestinal tract (can be taken, but with extreme caution).

Instructions for use

Meronem can only be used after consultation with your doctor. Only a specialist can determine the optimal schedule for taking the medication and select the most effective dosages. All these characteristics are selected based on the patient’s current health status and the severity of the disease.

For adults

Patients over 18 years of age tolerate this antibiotic much better than minors and children. Therefore, the duration of the course and the dosage of the medicine are large for them.

1. For gynecological diseases, pathologies of the urinary tract, pneumonia, as well as skin infections. Intravenous injections should be given (up to 500 mg per injection). Such procedures should be performed no more than three times a day. The frequency of injections and their number are determined by the attending physician.
2. For the treatment of peritonitis, nosocomial pneumonia, bacterial diseases (in people suffering from symptoms of neutropenia and septicemia). 1 gram of medicine per procedure. Injections should be given every 8 hours for 5-10 days.
3. For meningitis at any stage of the disease. The standard dose should be increased to 2 g. The frequency of intravenous injections is selected based on the stage of the disease and can vary from 1 to 3 times a day.
4. For people with impaired kidney function. For such diseases, it is recommended to reduce not only the dosage of the medication, but also the frequency of injections. These two parameters depend on the creatinine clearance rate. If it is less than 51 ml/min, you should switch to one-time injections of Meronem 500 mg. The drug is eliminated from the body during hemodialysis, so a new dose should be administered only after this procedure is completed.
5. For liver diseases. People with liver failure can use Meronem in the same way as others. In this case, no restrictions are provided.

Children and elderly patients

Otherwise, Meronem should be used for children and the elderly. They require special dosages and the right approach to choosing the number of injections.

Dosages:

1. Children from 3 months to 12 years. The dose for intravenous administration should be reduced to 10−20 mg/kg and calculated based on the child’s weight. If your body weight exceeds 50 kg, you can do “adult” injections. The frequency of injections is selected depending on the type of disease, stage, sensitivity of bacteria and the patient’s condition.
2. From 12 to 18 years old. Most often, a full dose of medication is administered. The only exception is adolescents weighing up to 50 kg. For them, a special amount of the drug is determined.
3. Aged people. The amount of medicine can be reduced only in case of problems with the kidneys and urinary system.

Pregnant and lactating women

It is especially important to correctly determine the dosage and duration of treatment with Meronem during pregnancy. A doctor's mistake can lead to the most serious health problems for the expectant mother and child. To prevent this from happening, the following rules must be taken into account:

1. The medicine can be administered intravenously only under the supervision of a specialist.
2. It is forbidden to use even minimal dosages if you are individually intolerant to the drug.
3. Injections should not be given if the positive effect of the medicine on the mother outweighs the potential risk to the child.

Meronem should not be used during breastfeeding. If this is not done, there is a high probability that the medicine will enter the baby’s body. In extreme cases, when antibiotic treatment is vital, the mother should avoid breastfeeding.

Side effects

If the medicine is taken incorrectly, some side effects may occur. However, serious pathologies are extremely rare.

The main ones:

1. Circulatory system. Patients often present with platelet count and eosinophilia. In rare cases, leukopenia, agranulocytosis, and anemia may occur.
2. Nervous system. In addition to headaches, rare hallucinations or fainting may occur. Meronem can increase anxiety, excitability or provoke depression. In rare cases, such disorders lead to insomnia.
3. Gastrointestinal tract. If the drug is used incorrectly, nausea, vomiting, diarrhea, and colitis may occur. Infrequent manifestations are constipation, cholestatic hepatitis.
4. Skin. A rash, hives, and severe itching may occur on the surface of the skin. Erythema multiforme and epidermal necrolysis sometimes occur.
5. The immune system. Meronem has virtually no effect, but can sometimes cause anaphylaxis and angioedema.
6. The cardiovascular system. The consequence of taking the medicine may be mild tachycardia or bradycardia. In the most extreme cases, heart failure, myocardial infarction, and cardiac arrest are possible.

In addition to all the side effects listed, thrombophlebitis, pain at the injection sites and minor inflammation may occur.

Interaction with other drugs

While taking Meronem, you should pay attention to its interactions with other drugs. Some combinations may cause side effects and significantly worsen your health.

1. Do not take Meronem with heparin.
2. The combined use of an antibiotic with nephrotoxic drugs increases the likelihood of dangerous complications.
3. Combination with valproic acid can reduce the effectiveness of combating pathogens.
4. Taking Meronem and probenecids contribute to the rapid removal of the antibiotic from the body and increases its concentration in the circulatory system.

Analogs

Drug manufacturers have developed several dozen analogues of Meronem. They all have a similar effect and differ only in cost. The price of the drug in Moscow can vary from 8 to 15 thousand rubles, depending on the size of the bottle.

Analogs of the product are more affordable for most patients and can cost around 2,000 rubles. The price of Meronem in St. Petersburg and other large cities of Russia is practically no different from Moscow.

The most popular analogues:

1. Medopenem. The medicine is produced in the form of a soluble powder for injection. Its main advantage is its low price, and its disadvantage is the presence of a large number of contraindications.
2. Invas. This drug works well against most harmful bacteria. It can be used for diabetes, but should not be taken if you are hypersensitive to lidocaine.
3. Merogram. Available in powder form for making a solution. The drug is much better tolerated than Meronem and has fewer side effects. Its only drawback is its relatively high price.

Meronem is a high-quality and effective medicine that helps cope with many harmful bacteria. If you use it correctly and follow all doctors’ recommendations, you don’t have to worry about any side effects and get cured as quickly as possible.

Before choosing analogues of Meronem, you must study the features of this drug, indications and contraindications for its use. This is an antibiotic that affects infections of bacterial origin of an aerobic and anaerobic nature.

The effect of using an antibiotic is achieved thanks to the main component, which freely penetrates the structure of bacteria and blocks the synthesis processes in pathogenic microorganisms.

Features of the drug

The medicine "Meronem" is a good antibacterial agent. It has an effective bactericidal effect, as it affects the synthesis of bacterial cells. The high level of activity of the main active substance against a wide range of aerobic and anaerobic infections is explained by the ability to penetrate the cellular structure.

The drug can be used as an independent drug or in combination with other drugs to enhance their therapeutic effect. Metabolism occurs in the liver. The drug "Meronem" penetrates quite well into almost all tissues of the body, which contributes to faster and more active treatment.

The elimination period of the drug is 1-1.5 hours, and the active substance can be detected in the urine for another 12 hours. Elderly people and those suffering from kidney failure require individual dosage adjustment of the medication. People with liver failure do not require dosage adjustment.

Composition and release form

The medicine is produced in the form of a powder intended for the preparation of injection solutions of 500 and 1000 mg in a bottle. The package contains 10 bottles. The active substance is meronem, and also contains other components.

The manufacturer of Meronem is the Japanese company Dainippon Sumitomo Pharmaceuticals Company. The medicine fully meets all quality and safety standards.

The use of "Meronem" is indicated for the treatment of diseases provoked by pathogens that are sensitive to this drug. These include:

• sepsis;
• inflammation of the genitourinary system;
• pneumonia;
• inflammation of the abdominal cavity;
• meningitis;
• inflammatory processes of the skin and soft tissues.

Also, the use of "Meronem" is justified in case of febrile temperature and reduced immunity. In this case, the medication is used for independent treatment and in combination with antiviral and antifungal drugs.

Features of application

According to the instructions for use, the antibiotic "Meronem" is prescribed to adults depending on the patient's condition, as well as the type and severity of the disease. To eliminate infections of the skin, urinary tract, endometritis, and pneumonia, injections of the drug are prescribed every 8 hours, 500 mg intravenously. You can also administer Meronem intramuscularly. In this case, the dosage and course of treatment are determined by the doctor.

According to the instructions, “Meronem” for the treatment of peritonitis, septicemia, pneumonia is prescribed 1 g intravenously every 8 hours. When treating meningitis, it is recommended to use 2 g. This dosage of “Meronem” has not been studied well enough.

When using the drug in elderly patients, there is no need to adjust the dose and duration of therapy, however, only on condition that they do not suffer from liver or kidney diseases.

Intravenous administration of "Meronem" is indicated for children from 3 months to 12 years. The dose is 10-20 mg/kg. The medicine must be administered every 8 hours, depending on the type of infection and the severity of the inflammatory process. The patient’s condition and the sensitivity of pathogens are also taken into account. Children weighing more than 50 kg are prescribed the same dosage as for adults. When treating meningitis, the drug must be administered every 8 hours. The dose of "Meronem" is 40 mg/kg.

For intravenous injections, the drug should be administered for at least 5 minutes. You can also use a dropper, in which case the duration of drug administration is 15-30 minutes. To dilute it, you need to use appropriate infusion fluids.

The concentration of the solution should be 50 mg per ml. It remains stable for 16 hours after its preparation. You need to follow the preparation rules, and also shake the bottle right before starting the procedure. It is recommended to use the drug "Meronem" for 5-15 days.

Contraindications and side effects

According to the instructions, Meronem is prohibited from being used in the following cases:

• children under 3 months;
• if the body is sensitive to antibacterial drugs;
• in case of intolerance to the components of the drug;
• gastrointestinal diseases and colitis;
• pregnancy and lactation.

Side effects after using this drug are rare. There is information about such consequences as:

• abdominal pain, nausea, bowel dysfunction;
• itching, skin rashes;
• anemia;
• cramps, headache;
• hypertension, tachycardia;
• allergy;
• inflammatory processes in the area of ​​drug administration;
• depression, insomnia, hallucinations.

According to the reference book of medicines or RLS, “Meronem” belongs to the group of antibacterial drugs. It helps cope with many pathogens. However, during its use the possibility of overdose cannot be ruled out. This mainly applies to patients who have kidney problems. In this case, hemodialysis and symptomatic treatment are prescribed.

special instructions

According to the instructions, the antibiotic “Meronem” is used in the treatment of many infectious diseases. If an infection in the respiratory system is suspected, it is recommended to conduct a sensitivity test. This also applies to patients who are critically ill and taking the drug as monotherapy.

Colitis is very rarely observed when taking this drug. Its forms and manifestations can range from mild to those that are life-threatening. If colitis occurs, you should stop taking the antibiotic. It is also important to use caution when taking this medication to people who have recurring seizures.

Sometimes patients complain of hypersensitivity from the drug and the appearance of allergies. When the first signs of an allergic reaction appear, you should stop taking Meronem and carry out appropriate treatment. The use of the drug in people with impaired liver function requires constant monitoring of bilirubin levels.

The use of the drug during pregnancy has not been studied. Those studies that were carried out on animals showed that Meronem does not cause any adverse effects in a newborn. However, it is still not recommended to use the medicine while pregnant, except in cases where its benefit to the woman significantly outweighs the likely risk to the fetus. In any case, therapy is carried out under strict medical supervision. If the dosage is exceeded, there is a risk of spontaneous abortion.

It is worth considering the possibility of dangerous consequences when using Meronem simultaneously with drugs that have a dangerous toxic effect on the kidneys. In addition, this medicine lowers valproic acid levels. Meronem is a prescription antibiotic. Shelf life is 4 years, subject to storage rules.

Analogues of the drug

Before using Meronem analogues, the instructions for use, indications and contraindications must be studied in order to prevent the occurrence of side effects. There are many drugs with a similar spectrum of action, and the main ones are the following:

• "Meropenem";
• "Merogram";
• "Invanz".

When choosing analogues of Meronem, you should pay attention to the drug Meropenem. It is produced in the form of a crystalline powder intended for the preparation of an injection solution. Another good remedy is Invanz. It helps to actively fight many pathogens, however, it is worth remembering that it is prohibited for use in treating children under 18 years of age.

The drug "Merogram" is available in the form of a powder intended for injection. It is much easier to tolerate than Meronem, and also causes much fewer allergic reactions.

The drug "Meropenem"

An analogue of Meronem is the drug Meropenem, which belongs to the carbapenem group of antibiotics and is used to treat various infectious and inflammatory processes provoked by sensitive pathogens. It demonstrates good results in the fight against many pathogens, so it can be used without bacteriological testing.

This medicine has pronounced antibacterial and bactericidal properties, so it can be used to treat infectious lesions of the genitourinary system.

The antibiotic is available in powder form, which is used to prepare a medicinal solution. It is packaged in 10 ml transparent glass bottles. The drug is used for:

• abdominal infections;
• pneumonia;
• gynecological infectious diseases;
• purulent skin lesions;
• sepsis;
• inflammation of the membranes of the brain;
• suspected of having a bacterial infection.

The drug is administered intravenously or intramuscularly very slowly. The contents of the bottle must first be diluted with 15 ml of water for injection. If infusion administration is necessary, the medicine is mixed with 50-200 ml of base. The dosage largely depends on the type of disease. The duration of the therapeutic course is determined separately for each patient and is generally 7-14 days.

The drug is not used if there is an individual intolerance to the components of this drug. Side effects include deterioration of health, loss of appetite, and the appearance of thrombophlebitis. It is not recommended to use the drug during pregnancy and lactation. Antibiotics can be used to treat infectious processes in children older than 3 months.

The drug "Invanz"

A good analogue of Meronem is the medicine Invanz. This is an antibiotic that is used to treat pneumonia, bacterial infections of the gastrointestinal tract, urinary system, and skin. In addition, it is used in the postoperative period.

The drug is administered intramuscularly or intravenously. The doctor selects the dosage and treatment regimen strictly individually. A contraindication for its use is individual intolerance to the components of the drug. It is also not recommended to use it during pregnancy and lactation.

Adults and children over 12 years of age are prescribed 1 g per day. The medicine can be used as an intravenous infusion, as well as an intramuscular injection. If a dropper is used, the duration of drug administration should be at least 30 minutes. Intramuscular injections are used if necessary or if intravenous administration is not possible. The duration of the therapeutic course ranges from 3 days to 2 weeks. If you feel better, you can switch to the oral form of taking antibacterial agents.

If renal function is impaired, the daily dosage of the drug "Invanz" must be adjusted. It is prohibited to mix the medicine or administer it simultaneously with other active substances. Side effects are rare and include diarrhea, headache, nausea, and venous disorders. Allergies are also possible. If it occurs, you need to stop using the drug and consult a doctor for urgent treatment.

During pregnancy, this drug is allowed to be used only if the benefit outweighs the likely risk to the fetus. Due to possible adverse reactions in a newborn, the use of the drug during lactation is not recommended.

The drug "Saironem"

To select an analogue of "Meronem", the instructions for use of the medicine must be carefully studied. In addition, consultation with the attending physician is required, since this is the only way to achieve the desired result and prevent complications.

Good analogues include the drug "Saironem", which is intended for the treatment of pneumonia, infections of the abdominal cavity, pelvic organs, urinary tract, and soft tissues. In addition, you can use the medicine to treat bronchitis.

The drug is produced in the form of a powder intended for the preparation of an injection solution. After administration, the medicine penetrates well into the tissues and spreads throughout the body. During pregnancy and lactation, treatment with this drug can be carried out only if the benefits to the mother outweigh the risks to the fetus. Side effects that should be noted include:

• nausea, diarrhea, vomiting;
• allergy;
• headache;
• local reactions.

When treating patients with liver disease, it is important to periodically test their bilirubin levels. In case of monotherapy or suspected lower respiratory tract infections, it is necessary to regularly test the sensitivity of the pathogen. The medicine should be used with caution in combination treatment with drugs that have a toxic effect on the kidneys.

The drug "Propinem"

This is an antibiotic of the carbapenem group. It exerts its bactericidal effect by disrupting the structure of bacteria. The drug is active against most pathogens. Some strains of staphylococcus and enterococci are resistant to the main substance of the drug.

The drug is used for intravenous and intramuscular administration, and quickly spreads throughout the body. Well suited for the treatment of infectious diseases caused by bacteria. Before using the medicine, you need to consult a doctor, and also undergo a mandatory examination of the body to make sure that there are no contraindications to its use.

During pregnancy and lactation, the use of the drug is possible only if the expected benefits of therapy for the mother significantly exceed the risks for the fetus. Among the contraindications, hypersensitivity to the main components of the drug should be highlighted. In some cases, side effects may occur, which include:

• abdominal pain, nausea and vomiting;
• increased bilirubin levels;
• the appearance of allergies;
• rashes, skin itching;
• headache, cramps.

In addition, thrombophlebitis may develop at the injection site, as well as pain and inflammation in the injection area.

When administered intravenously, a single dosage for adults ranges from 500 mg to 2 g, and the frequency and duration of use of the drug is determined individually, depending on the indications and severity of the disease. Children weighing less than 50 kg are prescribed 10-12 mg/kg. The drug is used every 8 hours. For children weighing more than 50 kg, the dosage is prescribed exactly the same as for adults.

When administered intramuscularly, it is recommended to use 500 mg every 8 hours, and for elderly people - 500 mg every 12 hours. In case of overdose, an increase in the symptoms of side effects is observed. In this case, symptomatic therapy is required. Sometimes hemodialysis may be needed.

The drug "Dzhenem"

It is prescribed for infectious diseases caused by bacteria. These include:

• pyelonephritis;
• peritonitis;
• endometritis;
• dermatosis;
• pneumonia;
• meningitis.

It is prohibited to use the drug for the treatment of infants under 3 months of age. Also a contraindication is intolerance to the components of the drug. During pregnancy, it is not recommended to use this medicine for therapy. However, in some cases it is still prescribed, namely, if the likely benefit to the mother significantly outweighs the risk of complications in the fetus. Therapy is carried out strictly under the supervision of a doctor. During therapy with this drug, you should definitely stop breastfeeding.

In some cases, side effects are observed that disappear after some time. If the patient's condition is severe, symptomatic therapy may be required. When taking the drug "Jenem" you may experience fainting, depression, hallucinations, insomnia, as well as many other negative manifestations.

Treatment of patients with liver problems should be carried out strictly under the supervision of a physician, and constant monitoring of bilirubin levels in the blood is required. During therapy, it is possible for pathogens to develop resistance to the active component of the drug. In this regard, long-term treatment should be carried out with constant monitoring of the prevalence of the main strains of bacteria.

In patients with gastrointestinal diseases, colitis may develop, the first sign of which is the appearance of signs of diarrhea during prolonged therapy. Before using the drug, you must consult your doctor, who will be able to choose the correct dosage and frequency of administration.

The drug "Meropenabol"

There are quite good analogues of Meronem in Russia, which include the drug Meropenabol. The main indications for its use are:

• respiratory infections;
• bacterial meningitis;
• abdominal infections;
• skin damage;
• sepsis;
• dysentery;
• bacterial endocarditis.

In addition, the use of medication is required if a bacterial infection is suspected in adults due to the development of neutropenia.

When the drug is administered intravenously at a dosage of 250 mg, the first therapeutic effect is achieved within 30 minutes. This remedy penetrates well into the body and spreads throughout all organs and tissues, including the cerebrospinal fluid, which is very important for patients with meningitis. The concentration required to suppress most bacteria is achieved within 0.5-1.5 hours from the start of its administration.

The drug undergoes metabolic processes in the liver. Approximately 70% is excreted through the kidneys within 12 hours. The dosage and duration of drug therapy is determined strictly individually, it all depends on the complexity of the disease and the general well-being of the patient.

For the treatment of gynecological diseases, urinary tract infections, and pneumonia, 500 mg of the drug is prescribed every 8 hours for intravenous administration. In the case of treatment of peritonitis, sepsis, and neutropenia, 1 g of the drug is required. When treating meningitis, the required dose is 2 g. Patients with kidney disease necessarily require adjustment of the dosage of the medication.

The active substance of the drug is removed during hemodialysis. If long-term therapy is required, it is recommended that the medication be administered after completion of the dialysis procedure. This is required to restore the optimal concentration of the antibiotic in the plasma.

For children from 3 months to 12 years, the dosage is 10-20 mg for each kg of the child’s weight. The medicine must be administered every 8 hours. However, the dose and frequency of use can be adjusted depending on the type of disease and the severity of the infection.

This is almost a complete analogue of “Meronem” in Russia, since the medicine contains the same active substance. When using the drug, accidental overdose is possible. In this case, symptomatic treatment is required. The safety of the drug during pregnancy has not been determined. It is recommended to stop lactation during therapy.

INN: Meropenem

Manufacturer: ACS Dobfar S.P.A.

Anatomical-therapeutic-chemical classification: Meropenem

Registration number in the Republic of Kazakhstan: No. RK-LS-5No. 017669

Registration period: 29.07.2016 - 29.07.2021

KNF (medicine included in the Kazakhstan National Formulary of Medicines)

ED (Included in the List of drugs within the framework of the guaranteed volume of free medical care, subject to purchase from the Single Distributor)

Limit purchase price in the Republic of Kazakhstan: 8 305.15 KZT

Instructions

Tradename

International nonproprietary name

Meropenem

Dosage form

Lyophilisate for the preparation of solution for intravenous administration

Compound

One bottle contains

active substance - meropenem trihydrate 570 mg and 1140 mg (equivalent to meropenem anhydrous 500 mg and 1000 mg)

excipient - sodium carbonate anhydrous 104 mg and 208 mg respectively.

Description

Powder from white to light yellow, free from visible mechanical inclusions.

Pharmacotherapeutic group

Antimicrobials for systemic use. Other betalactam antibacterial drugs. Carbapinemas. Meropenem.

Code ATXJ01DH02

Pharmacological properties

Pharmacokinetics

In healthy individuals, the average elimination half-life is approximately 1 hour; the mean volume of distribution is about 0.25 L/kg (11-27 L), and the mean clearance is 239 ml/min at a dose of 500 mg and decreases to 205 ml/min at a dose of 2 g. Doses of 500, 1000 and 2000 mg, administered over 30 min, lead to mean Cmax values ​​of about 23, 49 and 115 μg/ml, respectively, corresponding to AUC values ​​of 39.3; 62.3 and 153 mcg*h/ml. After infusion of 500 and 1000 mg doses over 5 minutes, Cmax values ​​were 52 and 112 μg/ml, respectively. When multiple doses are administered at 8-hour intervals to patients with normal renal function, meropenem does not accumulate.

A study of 12 patients who were administered meropenem 1000 mg every 8 hours after surgery for the treatment of intra-abdominal infections showed that these patients had Cmax and half-life values ​​comparable to those in healthy subjects, but the volume of distribution was 27 L.

Distribution

The average binding of meropenem to plasma proteins is approximately 2% and is independent of its concentration. Meropenem penetrates well into several body fluids and tissues: including the lungs, bronchial secretions, bile, cerebrospinal fluid, genital tissues, skin, fascia, muscles, and peritoneal exudate.

Metabolism

Meropenem is metabolized by hydrolysis of the β-lactam ring to form a microbiologically inactive metabolite. Unlike imipenem, meropenem in conditions in vitro demonstrates low sensitivity to hydrolysis by human dehydropeptidase-1 (DHP-1) and does not require additional administration of a DHP-1 inhibitor

Removal

Meropenem is excreted primarily unchanged by the kidneys, with approximately 70% (50-75%) of the dose excreted unchanged within 12 hours. Another 28% is excreted as an inactive metabolite. Excretion in feces is only about 2% of the dose. Measurements of renal clearance and the effect of probenecid indicate that meropenem undergoes both filtration and tubular secretion.

The pharmacokinetics of meropenem in children and adults are similar. The half-life of meropenem in children under 2 years of age is approximately 1.5 - 2.3 hours, with a linear relationship observed in the dose range of 10 - 40 mg/kg.

Pharmacokinetic studies in patients with renal failure have shown that meropenem clearance correlates with creatinine clearance. In such patients, dose adjustment is necessary.

Pharmacokinetic studies in elderly subjects revealed a decrease in meropenem clearance, which correlated with an age-related decrease in creatinine clearance.

A study of patients with alcoholic cirrhosis showed that this liver disease did not affect the pharmacokinetics of meropenem when administered multiple times.

Pharmacodynamics

Meronem is an antibiotic of the carbapenem class, intended for parenteral use, relatively resistant to human dehydropeptidase-1 (DHP-1), and does not require additional administration of a DHP-1 inhibitor.

Meronem has a bactericidal effect due to its effect on the synthesis of the bacterial cell wall. The bactericidal effect of Meronem against a wide range of aerobic and anaerobic bacteria is explained by Meronem's high ability to penetrate the bacterial cell wall, a high level of resistance to most β-lactamases and significant affinity for penicillin-binding proteins (PBPs). Minimum bactericidal concentrations (MBCs) are usually the same as minimum inhibitory concentrations (MICs). For 76% of the bacterial species tested, the MBC/MIC ratio was 2 or less.

Meroneme is stable in pathogen sensitivity tests. Meronem acts synergistically with various antibiotics. Meronem also has a post-antibiotic effect.

Spectrum of antibacterial activity of Meronem based on clinical experience and therapeutic recommendations includes the following types:

Gram-positive aerobes:

Enterococcusfaecalis(E. faecalis may be intermediate in nature) Staphylococcus aureus(methicillin-sensitive strains only: methicillin-resistant staphylococci, including MRSA, are resistant to meropenem) , species of the genus Staphylococcus, including Staphylococcus epidermidis(only methicillin-sensitive strains: methicillin-resistant staphylococci, including MRSE, show resistance to meropenem), Streptococcus agalactiae(group B streptococci), group Streptococcus milleri(WITH.anginosus, S . constellatus, WITH.intermedius), Streptococcus pneumoniae,Streptococcus pyogenes (group A streptococci)

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, Serratiamarcescens.

Anaerobic gram-positive bacteria:

Clostridium perfringens, Peptoniphilus asaccharolyticus, Peptostreptococcus species(including P. micros, P. anaerobius, P. magnus).

Anaerobic gram-negative bacteria

Bacteroides caccae, Bacteroides fragilis, Prevotella bivia, Prevotella disiens

Species for which acquired resistance may be a problem:

Gram-positive aerobes

Enterococcus faecium

Gram-negative aerobes

Acinetobacter spp, Burkholderia cepacia, Pseudomonas aeruginosa

Initially resistant microorganisms

Gram-negative aerobes

Stenotrophomonas maltophilia, Legionella spp.

Other intrinsically resistant microorganisms

Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Mycoplasma Pneumoniae

The prevalence of acquired resistance may vary geographically and temporally among individual species, so local information on resistance is desirable, especially when treating severe infections.

IndicationsToapplication

Meronem for intravenous administration is indicated for the treatment of the following infections in children and adults caused by one or more pathogens susceptible to meropenem:

Pneumonia, including hospital-acquired

Urinary tract infections

Abdominal infections

Gynecological infections such as endometritis and inflammatory

diseases of the pelvic organs

Skin and soft tissue infections

Meningitis

Septicemia

Empirical treatment as monotherapy or combination with

antiviral or antifungal agents if you suspect

adult patients for infection with symptoms of febrile neutropenia.

Meronem has shown effectiveness as monotherapy or in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Meronem for intravenous administration is effectively used in patients with cystic fibrosis (cystic fibrosis) and chronic lower respiratory tract infections as monotherapy or in combination with other antibacterial agents.

There is no experience with the use of the drug in pediatric practice in patients with neutropenia or with primary or secondary immunodeficiency.

Directions for use and doses

The dosage and duration of therapy should be based on the type and severity of the infection and the patient's condition.

500 mg IV every 8 hours for the treatment of pneumonia, urinary tract infections, gynecological infections such as endometritis, skin and soft tissue infections.

1 g intravenously every 8 hours for the treatment of hospital-acquired pneumonia, peritonitis, suspected bacterial infection in patients with symptoms of neutropenia, as well as septicemia.

For infection caused by Pseudomonas aeruginosa, the recommended dose is at least 1 g every 8 hours for adults (maximum permissible dose is 6 g per day, divided into 3 doses), and at least 20 mg/kg every 8 hours for children (maximum permissible dose is 120 mg/kg per day, divided into 3 doses).

Dosage in adult patients with impaired renal function

In patients with creatinine clearance less than 50 ml/min, the dose should be reduced as follows:

Creatinine clearance Dose Frequency of administration

(ml/min) (based on unit doses of 500 mg, 1 g, 2 g)

26 - 50 one dose unit every 12 hours

10 - 25 0.5 dose units every 12 hours

 10 0.5 dose units every 24 hours

Meronem is excreted by hemodialysis and hemofiltration. If long-term treatment with Meronem is required, it is recommended that a unit dose (based on the type and severity of infection) be administered at the end of the hemodialysis procedure to restore effective plasma concentrations.

Dosage in adult patients with impaired liver function

There is no need for dose adjustment in patients with liver failure.

Elderly patients

In elderly patients with normal renal function or creatinine clearance more than 50 ml/min, no dose adjustment is required.

Children

For children aged 3 months to 12 years, the recommended dose for intravenous administration is 10 - 20 mg/kg every 8 hours depending on the type and severity of infection, the sensitivity of the pathogen and the patient's condition.

In children weighing more than 50 kg, dosages recommended for adults should be used.

In children aged 4 to 18 years suffering from cystic fibrosis (cystic fibrosis), during periods of exacerbation of chronic lower respiratory tract infections, dosages of 25 to 40 mg/kg are used every 8 hours.

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

Method of administration

Meronem for intravenous use can be administered as an intravenous bolus injection over at least 5 minutes, or as an intravenous infusion over 15 to 30 minutes, using appropriate infusion fluids for dilution.

Meronem for intravenous bolus injections should be diluted with sterile water for injection (10 ml per 500 mg of meropenem), with a drug concentration of approximately 50 mg/ml. The resulting solution is a clear, colorless or light yellow liquid.

There is limited data to support the safety of bolus doses of 2g in adults and 40mg/kg in children.

Meronem for intravenous infusion can be diluted with a compatible infusion fluid equal to 50 mg/ml.

Meronem should not be mixed or added to other drugs.

Meronem is compatible with the following infusion solutions:

0.9% sodium chloride solution

5% or 10% glucose solution (dectrose).

When diluting Meronem, the standard antiseptic regimen should be followed. Shake the diluted solution before use.

All bottles are for single use only.

Meronem solution should not be frozen.

Side effects

Often

Thrombocythemia

Headache

Nausea, vomiting, diarrhea

Increased concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and γ-glutamyltransferase in blood serum

Rash, itching

Inflammation and pain at the injection site

Infrequently

Oral candidiasis and vaginal candidiasis

Eosinophilia, thrombocytopenia, leukopenia, neutropenia

Paresthesia

Increased serum bilirubin concentration

Hives

Thrombophlebitis

Rarely

Convulsions

Agranulocytosis

Very rarely

Hemolytic anemia

- Quincke's edema, manifestations of anaphylaxis

Pseudomembranous colitis

Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis

Anorexia

Increased excitability, agitation, restlessness, depression, hallucinations, anxiety, insomnia

Peripheral edema, dysuria, hematuria, renal dysfunction

Reversible thrombocytosis, eosinophilia, thrombocytopenia, leukopenia

Quincke's edema

Convulsions

Epileptiform seizures

Cholestatic hepatitis, hyperbilirubinemia, jaundice

Cardiac arrest, heart failure, tachycardia, bradycardia, shortness of breath, decreased or increased blood pressure, myocardial infarction, pulmonary embolism

Contraindications

History of hypersensitivity to meropenem and other components of the drug, including other beta-lactam antibacterial agents

Pregnancy and lactation

Children up to 3 months of age (efficacy and safety for this

patient groups were not studied).

Carefully:

simultaneous administration of Meronem with potentially nephrotoxic drugs. Persons with gastrointestinal diseases, especially those suffering from colitis.

Drug interactions

Probenecid competes with Meronem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and plasma concentration of Meronem. Because the efficacy and duration of action of Meronem administered without probenecid are adequate, coadministration of probenecid with Meronem is not recommended.

The possible effects of Meronem on the protein binding or metabolism of other drugs have not been studied. Meronem's protein binding is low (about 2%), and it is assumed that there should be no interaction with other drugs based on displacement from plasma proteins.

Meronem may reduce serum levels of valproic acid. Concomitant use of valproic acid/sodium valproate with Meronem is not recommended.

The use of Meronem while taking other drugs was not accompanied by the development of adverse pharmacological interactions. However, there is no specific data on possible drug interactions (with the exception of probenecid).

special instructions

When using Meronem as monotherapy, as with the use of other antibiotics, in patients who are critically ill with an identified lower respiratory tract infection caused by Pseudomonas aeruginosa or if it is suspected, regular sensitivity testing to this antibiotic and caution in use are recommended.

In rare cases, when using Meronem, as with the use of almost all antibiotics, the development of pseudomembranous colitis is observed, which can vary in severity from mild to life-threatening forms. Therefore, patients with gastrointestinal diseases, especially colitis, should be prescribed antibiotics with extreme caution. It is important to keep in mind the diagnosis of “pseudomembranous colitis” if diarrhea develops while taking Meronem. Although research has shown that the toxin produced Clostridium difficile, is one of the main causes of colitis associated with the use of antibiotics, however, it is necessary to keep in mind other causes.

There is evidence of partial cross-allergenicity between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. Before starting Meronem therapy, the patient should be carefully interviewed, paying special attention to a history of hypersensitivity reactions to beta-lactam antibiotics. Meronem should be used with caution in patients with a history of such phenomena. If an allergic reaction to Meronem occurs, it is necessary to stop administering the drug and take appropriate measures.

The use of Meronem in patients with liver disease should be carried out under careful monitoring of transaminase and bilirubin levels.

As with other antibiotics, predominant growth of insensitive microorganisms is possible, and therefore constant monitoring of the patient is necessary.

The use of the drug for infections caused by methicillin-resistant staphylococcus is not recommended.

Pregnancy and lactation

The safety of Meronem in women during pregnancy has not been studied. Meronem should not be used during pregnancy unless the potential benefit justifies the possible risk to the fetus. In each case, the drug must be used under the direct supervision of a physician.

Meronem should not be used in breastfeeding women unless the potential benefit justifies the possible risk to the baby. If it is necessary to use the drug during lactation, you should consider stopping breastfeeding.

Use in pediatrics

The effectiveness and tolerability of the drug in children under 3 months of age has not been assessed, and therefore the use of the drug in children under this age is not recommended. There is no experience with the use of the drug in children with impaired liver and kidney function, in patients with neutropenia, or with primary and secondary immunodeficiency.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Special studies of the effect of Meronem on the ability to drive a car and other equipment have not been conducted, however, the possibility of developing headaches, convulsions and paresthesia when using Meronem should be taken into account.

Overdose

Accidental overdose during treatment is possible, especially when treating patients with impaired renal function.

Symptoms: increased side effects of the drug.

Treatment: symptomatic. In patients with normal renal function, the drug is rapidly excreted in the urine. Hemodialysis is effective in patients with renal impairment.

Release form and packaging

The drug with a dosage of 0.5 g is placed in clear glass vials with the AstraZeneca logo with a capacity of 20 ml or with a dosage of 1 g in clear glass vials with the AstraZeneca logo with a capacity of 30 ml, sealed with rubber stoppers and crimped with aluminum caps with a blue plastic cap (for a dosage of 0.5 g ) or garnet color (for a dosage of 1 g).

10 bottles along with instructions for use in the state and Russian languages ​​are placed in a cardboard pack.

Storage conditions

Store at temperatures below 30°C.

Keep out of the reach of children!

Shelf life

4 years Do not use after the expiration date stated on the package.

Conditions for dispensing from pharmacies

On prescription

Manufacturer

ACS Dobfar S.P.A., Italy

Marketing Authorization Holder/Packer

AstraZeneca UK Limited, UK

Address of the organization receiving complaints from consumers regarding the quality of products (goods) in the territory of the Republic of Kazakhstan

Representative office of ZAK “AstraZeneca UK Limited”

Phone: +7 727 226 25 30

Fax: +7 727 226 25 29

e-mail: adverse.events.kz @astrazeneca.com

Meronem is a trademark owned by the AstraZeneca group of companies.

Attached files

Dosage form: powder for the preparation of solution for intravenous administration

Compound
One bottle contains:

Meronem® 0.5 g Meronem® 1 g
Active Ingredient:
meropenem trihydrate 570 mg 1140 mg
equivalent to anhydrous meropenem 500 mg 1000 mg
Auxiliary ingredient:
sodium carbonate (anhydrous) 104 mg 208 mg

Description
Powder from white to light yellow.

Pharmacotherapeutic group
Antibiotic, carbapenem

ATX code: J01DH02

Pharmacological properties
Pharmacodynamics
Meropenem is an antibiotic of the carbapenem class, intended for parenteral use, relatively resistant to human dehydropeptidase-1 (DHP-1), and does not require additional administration of a DHP-1 inhibitor.
Meropenem has a bactericidal effect due to its effect on the synthesis of the bacterial cell wall. The high bactericidal activity of meropenem against a wide range of aerobic and anaerobic bacteria is explained by the high ability of meropenem to penetrate the bacterial cell wall, a high level of stability to most b-lactamases and significant affinity for various penicillin-binding proteins (PBPs). Minimum bactericidal concentrations (MBCs) are usually the same as minimum inhibitory concentrations (MICs). For 76% of the bacterial species tested, the MBC/MIC ratio was 2 or less.
In vitro tests show that meropenem acts synergistically with various antibiotics. In vitro and in vivo tests have shown that meropenem has a post-antibiotic effect.
Microorganisms may have one or more of the following mechanisms of resistance to meropenem: impaired permeability of the cell wall of gram-negative bacteria due to impaired porin synthesis; decreased affinity for target PBPs; activation of efflux mechanisms; production of beta-lactamases, under the influence of which hydrolysis of carbapenems occurs.
The only recommended criteria for sensitivity to meropenem are based on the pharmacokinetics of the drug and on the correlation of clinical and microbiological data - zone diameter and MIC determined for the relevant pathogens.
The sensitivity threshold for Streptococcus pneumoniae and Haemophilus influenzae for meningitis is 0.25 mg/l.
Strains for which the MIC is above the sensitivity threshold are rare or not currently detected. If such a strain is detected, the MIC test is repeated; when the result is confirmed, the strain is sent to a reference laboratory, and the strain is considered resistant until a confirmed clinical effect is obtained regarding it.
Values ​​used for meningitis only.
For all other pathogens, according to pharmacokinetic and pharmacodynamic data, without taking into account the specific distribution of MICs of specific pathogens.
Susceptibility testing is not recommended because this pathogen is not an optimal target for meropenem.
Susceptibility to meropenem should be determined using standard methods. Interpretation of results should be done in accordance with local guidelines.
The effectiveness of the drug against the pathogens listed below is confirmed by clinical experience and guidelines for antibacterial therapy:
Pathogens sensitive to meropenem:
Gram-positive aerobes:
Enterococcus faecalis1
Staphylococcus aureus (methicillin-sensitive)2
Genus Staphylococcus (methicillin-sensitive), including Staphylococcus epidermidis
Streptococcus agalactiae group B
Streptococcus milleri group (S. anginosus, S. constellatus, 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
Genus Peptostreptococcus (including P. micros, P anaerobius, P. magnus)
Gram-negative anaerobes:
Bacteroides caccae
Bacteroides fragilis
Prevotella bivia
Prevotella disiens
Pathogens for which the problem of acquired resistance is relevant:
Gram-positive aerobes:
Enterococcus faecium1
Gram-negative aerobes:
Genus Acinetobacter
Burkholderia cepacia
Pseudomonas aeruginosa
Pathogens with natural resistance:
Gram-negative aerobes:
Stenotrophomonas maltophilia
Legionella spp.
Other pathogens:
Chlamydophila pneumoniae
Chlamydophila psittaci
Coxiella burnetii
Mycoplasma pneumoniae
Pathogens with intermediate sensitivity.
All methicillin-resistant staphylococci are resistant to meropenem.

Pharmacokinetics
Intravenous administration of Meronem® over 30 minutes to healthy volunteers results in maximum plasma concentrations of approximately 11 mcg/ml for a 250 mg dose, 23 mcg/ml for a 500 mg dose and 49 mcg/ml for a 1 g dose.
However, with respect to maximum concentration (Cmax) and area under the concentration-time curve (AUC), there is no absolute pharmacokinetic proportionality to the administered dose. There was a decrease in plasma clearance from 287 to 205 ml/min for doses from 250 mg to 2 g.
Intravenous bolus injection of Meronem® into healthy volunteers over 5 minutes results in maximum plasma concentrations of approximately 52 mcg/mL for a 500 mg dose and 112 mcg/mL for a 1 g dose.
6 hours after intravenous administration of 500 mg, the concentration of meropenem in the blood plasma decreases to values ​​of 1 mcg/ml and below.
Extended (up to 3 hours) infusion of carbapenems can lead to optimization of their pharmacokinetic and pharmacodynamic parameters. With a standard 30-minute infusion in healthy volunteers of two doses of 500 and 2000 mg every 8 hours, the %T>MIC value (the ratio between the period of time when the drug concentration exceeds the MIC and the dosing interval; MIC = 4 μg/ml) was 30%, respectively. and 58%. When the same doses were administered to volunteers by 3-hour infusion every 8 hours, the %T>MIC increased to 43 and 73%, for 500 and 2000 mg, respectively. The mean plasma concentration in healthy volunteers following a 10-minute intravenous bolus of 1000 mg exceeded the MIC of 4 μg/mL for 42% of the dosing interval compared with 59% for a 3-hour infusion of 1000 mg.
Meropenem penetrates well into most body tissues and fluids, including the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations greater than those required to inhibit most bacteria.
With repeated administration of meropenem at intervals of 8 hours to patients with normal renal function, no accumulation of the drug is observed. In patients with normal renal function, the half-life is approximately 1 hour.
Plasma protein binding is approximately 2%.
About 70% of an intravenous dose of Meronem® is excreted unchanged by the kidneys within 12 hours, after which negligible renal excretion is determined. Urinary meropenem concentrations greater than 10 mcg/mL are maintained for 5 hours after a 500 mg dose. With dosing regimens of 500 mg every 8 hours or 1 g every 6 hours, no accumulation of meropenem in plasma or urine was observed in volunteers with normal liver function.
The only metabolite of meropenem is microbiologically inactive.
Studies in children have shown that the pharmacokinetics of Meronem® in children and adults is similar. The half-life of meropenem in children under 2 years of age is approximately 1.5-2.3 hours, with a linear relationship observed in the dose range of 10-40 mg/kg.
Kidney failure
Pharmacokinetic studies in patients with renal failure have shown that meropenem clearance correlates with creatinine clearance. In such patients, dose adjustment is necessary.
Pharmacokinetic studies in elderly subjects revealed a decrease in meropenem clearance, which correlated with an age-related decrease in creatinine clearance.
Meropenem is eliminated by hemodialysis with a clearance approximately 4 times higher than the clearance of meropenem in anuric patients.
Liver failure
Pharmacokinetic studies in patients with liver disease have shown that these pathological changes do not affect the pharmacokinetics of meropenem.

Indications for use
Meronem® is indicated for the treatment in children (over 3 months) and adults of the following infectious and inflammatory diseases caused by one or more pathogens sensitive to meropenem:
- pneumonia, including nosocomial pneumonia;
- infections of the urinary system;
- abdominal infections;
- infectious and inflammatory diseases of the pelvic organs, such as endometritis;
- infections of the skin and its structures;
- meningitis;
- septicemia.
Empirical treatment of adult patients with suspected infection and symptoms of febrile neutropenia, either alone or in combination with antiviral or antifungal drugs.
The effectiveness of Meronem® has been proven both in monotherapy and in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Contraindications
History of hypersensitivity to meropenem or other drugs of the carbapenem group.
Severe hypersensitivity (anaphylactic reactions, severe skin reactions) to any antibacterial agent having a beta-lactam structure (i.e. penicillins or cephalosporins).
Children under 3 months.

Carefully
Concomitant use with potentially nephrotoxic drugs.
Patients with complaints from the gastrointestinal tract (diarrhea), especially those suffering from colitis.

Use during pregnancy and breastfeeding
Pregnancy
The safety of Meronem® in women during pregnancy has not been studied. Animal studies have not shown any adverse effects on the developing fetus.
Meronem® should not be used during pregnancy unless the potential benefit to the mother outweighs the possible risk to the fetus. In each case, the drug must be used under the strict supervision of a physician.
Breastfeeding period
Data have been obtained on the excretion of meropenem in breast milk. Meronem® should not be used during breastfeeding, unless the potential benefit to the mother from using the drug outweighs the possible risk to the baby. Having assessed the benefit for the mother, a decision should be made to stop breastfeeding or to discontinue the drug Meronem®.

Directions for use and doses
Adults
The dose and duration of therapy should be based on the type and severity of the infection and the patient's condition.
The following daily doses are recommended:
500 mg IV every 8 hours for the treatment of pneumonia, urinary tract infections, gynecological infections such as endometritis, infections of the skin and skin structures;
1 g intravenously every 8 hours for the treatment of nosocomial pneumonia, peritonitis, suspected bacterial infection in patients with symptoms of neutropenia, and septicemia.
For the treatment of meningitis, the recommended dose is 2 g every 8 hours.
For the treatment of certain infections, particularly those caused by less sensitive pathogens (such as Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.), or for very severe infections, the recommended dose is up to 2 g every 8 hours.
The safety of the 2 g dose as a bolus injection has not been sufficiently studied.
Dose in adult patients with impaired renal function
In patients with creatinine clearance less than 51 ml/min, the dose should be reduced as follows:

Creatinine clearance (ml/min) - Dose (based on 500 mg, 1 g, 2 g dose unit) - Frequency of administration
26-50 one dose unit every 12 hours
10-25 0.5 dose units every 12 hours
< 10 0,5 единицы дозы каждые 24 часа

Meropenem is eliminated by hemodialysis and hemofiltration. If long-term treatment with Meronem® is required, it is recommended that the drug (depending on the type and severity of infection) be administered at the end of the hemodialysis procedure to restore effective plasma concentrations.
There are currently no data on experience with the use of Meronem® for administration to patients undergoing peritoneal dialysis.
Dosing in Adult Patients with Hepatic Impairment
In patients with liver failure, there is no need for dose adjustment (see section "Special Instructions").
Elderly patients
In elderly patients with normal renal function or creatinine clearance more than 50 ml/min, no dose adjustment is required.
Children
For children aged 3 months to 12 years, the recommended intravenous dose is 10-20 mg/kg every 8 hours depending on the type and severity of infection, the sensitivity of the pathogen and the patient's condition.
In children weighing more than 50 kg, adult doses should be used.
For meningitis, the recommended dose is 40 mg/kg every 8 hours.
For the treatment of certain infections, particularly those caused by less sensitive pathogens (such as Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp.), or for very severe infections, the recommended dose is up to 40 mg/kg every 8 hours.
The safety of the 40 mg/kg bolus dose has not been sufficiently studied.
There is no experience in using the drug in children with impaired liver and kidney function.
Method of administration
Meronem® for intravenous use can be administered as an intravenous bolus injection over at least 5 minutes, or as an intravenous infusion over 15-30 minutes; Appropriate infusion fluids should be used for dilution.
The possibility of using meropenem in an extended infusion mode (up to 3 hours) is based on pharmacokinetic and pharmacodynamic parameters (see section “Pharmacokinetics”). To date, clinical and safety data supporting this regimen are limited.
To prepare a solution for intravenous bolus injections, Meronem® should be dissolved in sterile water for injection (5 ml per 250 mg of meropenem), and the concentration of the solution is 50 mg/ml. The resulting solution remains stable for 3 hours at temperatures up to 25°C and for 16 hours when stored in the refrigerator (2-8°C).
To prepare a solution for intravenous infusion, Meronem® should be dissolved in 0.9% sodium chloride solution for infusion or 5% dextrose (glucose) solution for infusion, and the concentration of the solution should be from 1 to 20 mg/ml. The resulting solution remains stable for 3 hours at temperatures up to 25°C and for 24 hours when stored in a refrigerator (2-8°C), if a 0.9% sodium chloride solution was used for its preparation. The solution prepared using 5% glucose solution should be used immediately.
The Meronem® solution should not be frozen.
It is recommended to administer the prepared solution immediately after preparation (from a microbiological point of view), if the conditions for preparing the solution do not exclude the possibility of microbiological contamination.

Side effect
In general, meropenem is well tolerated. In rare cases, side effects led to discontinuation of therapy. Serious adverse reactions are rare.
The frequency of adverse reactions is shown in the table as follows: very often (≥1/10); often (≥1/100,<1/10); нечасто (≥1/1000, <1/100); редко (≥1/10000, <1/1000); очень редко (<1/10000); неуточненной частоты (частота не может быть определена на основании имеющихся данных).
Organs and systems
Side effects
Hematopoietic system*
Common: thrombocytosis
Uncommon: eosinophilia, thrombocytopenia
Rare: leukopenia, neutropenia, agranulocytosis
Very rare: hemolytic anemia
Nervous system
Uncommon: headache, paresthesia, syncope**, hallucinations**, depression**, anxiety**, irritability**, insomnia**
Rarely: seizures
Gastrointestinal tract
Often: nausea, vomiting, diarrhea, increased activity of liver transaminases, alkaline phosphatase, lactate dehydrogenase and bilirubin concentration in the blood serum
Uncommon: constipation**, cholestatic hepatitis**
Very rare: pseudomembranous colitis
Skin and subcutaneous tissue
Uncommon: rash, urticaria, pruritus
Very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Unspecified frequency: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
The immune system
Very rare: angioedema, manifestations of anaphylaxis
The cardiovascular system
Uncommon: heart failure**, cardiac arrest**, tachycardia**, bradycardia**, myocardial infarction**, decreased or increased blood pressure (BP)**, thromboembolism of pulmonary artery branches**
Kidneys and urinary tract
Uncommon: increased blood creatinine concentration, increased blood urea concentration
Respiratory tract
Uncommon: dyspnea**
Others
Often: local reactions - inflammation, thrombophlebitis, pain at the injection site
Rare: vaginal candidiasis and candidiasis of the oral mucosa
*Cases of a positive direct or indirect Coombs test, as well as cases of decreased partial thromboplastin time, have been reported.
**A cause-and-effect relationship with taking Meronem® has not been established. Adverse effects were observed in a study of 2904 immunocompetent adult patients treated with Meronem (500 mg or 1000 mg every 8 hours) due to non-CNS infections. In 36 patients, therapy was discontinued due to adverse events. In 5 cases, a connection between the death and the therapy cannot be ruled out. Given the serious condition of the patients, numerous diseases and multiple concomitant therapy with other drugs, it was not possible to draw a conclusion about the connection of the side effect with therapy with Meronem®.

Overdose
Accidental overdose during treatment is possible, especially in patients with impaired renal function.
Treatment in case of overdose should be symptomatic. Normally, the drug is rapidly eliminated through the kidneys. In patients with impaired renal function, hemodialysis effectively removes meropenem and its metabolite.

Interaction with other drugs
Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and plasma concentration of meropenem. Since the efficacy and duration of action of Meronem® administered without probenecid are adequate, coadministration of probenecid with Meronem® is not recommended.
The possible effect of Meronem® on the degree of binding of other drugs to plasma proteins or metabolism has not been studied. The binding of Meronem® to plasma proteins is low (about 2%), therefore, interaction with other drugs based on the mechanism of displacement from plasma proteins is not expected.
Co-administration of carbapenems and valproic acid preparations led to a decrease in the concentration of valproic acid in the blood plasma by 60-100% after 2 days of therapy. Due to the rapid and significant decrease in the concentration of valproic acid, co-administration of Meronem® and valproic acid preparations is not recommended.
The use of Meronem® while taking other drugs was not accompanied by the development of adverse pharmacological interactions. Studies examining the interaction of meropenem with other drugs (except probenecid) have not been conducted.
Cases of increased anticoagulant effect have been repeatedly reported when indirect anticoagulants (for example, warfarin) and antibacterial drugs are taken together. The risk of increased anticoagulant effect may depend on the nature of the infection, age and general condition of the patient, so it is difficult to assess the effect of an antibacterial drug on increasing the international normalized ratio (INR).
Frequent INR monitoring is recommended during co-administration of an antibacterial drug and an indirect anticoagulant and for some time after its cessation.

special instructions
There is no experience with the use of the drug in pediatric practice in patients with neutropenia or with primary or secondary immunodeficiency.
As with other antibiotics, regular susceptibility testing is recommended when meropenem is used as monotherapy in critically ill patients with known or suspected lower respiratory tract infection caused by Pseudomonas aeruginosa.
In rare cases, when using the drug Meronem®, as with the use of almost all antibiotics, the development of pseudomembranous colitis is observed, which can vary in severity from mild to life-threatening forms. It is important to remember the possibility of developing pseudomembranous colitis if diarrhea occurs while using the drug Meronem®. If pseudomembranous colitis develops, Meronem® should be discontinued. The use of drugs that inhibit intestinal motility is contraindicated.
Convulsions have been reported infrequently with the use of carbapenems, including meropenem. Caution should be exercised when using Meronem® in patients with a reduced seizure threshold.
There are clinical and laboratory signs of cross-allergic reactions between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. There are rare reports of cases of hypersensitivity reactions (including fatal ones) when using the drug Meronem®, as well as other beta-lactam antibiotics (see section “Side effects”). Before initiating meropenem therapy, the patient should be carefully interviewed, paying particular attention to any history of hypersensitivity reactions to beta-lactam antibiotics. Meronem should be used with caution in patients with a history of hypersensitivity reactions to beta-lactam antibiotics (i.e. penicillins and cephalosporins). If an allergic reaction to meropenem occurs, it is necessary to stop administering the drug and take appropriate measures.
The use of Meronem® in patients with liver disease should be carried out under careful monitoring of transaminase activity and bilirubin concentration.
As with other antibiotics, overgrowth of non-susceptible microorganisms is possible, and therefore constant monitoring of the patient is necessary.
The prevalence of acquired antibiotic resistance of various pathogens may vary depending on the region and over time, and it is desirable to have up-to-date information on the resistance of common pathogens in a particular region, especially when treating severe infections. If resistance is such that the effectiveness of the drug against at least some infections becomes doubtful, an expert should be consulted.
Co-administration of Meronem® and valproic acid preparations is not recommended due to a possible decrease in the concentration of valproic acid in the blood serum. In some patients, subtherapeutic concentrations may be achieved (see section "Interaction with other drugs").
The use of the drug for infections caused by methicillin-resistant staphylococcus is not recommended.

Impact on the ability to drive a car and operate equipment
There have been no studies of the effect of Meronem® on the ability to drive a car or use other equipment. However, it should be taken into account that headache, paresthesia and convulsions may occur when taking Meronem®.

Release form
Powder for the preparation of solution for intravenous administration, 0.5 g and 1 g.
0.5 g of active substance in glass bottles with a capacity of 10 ml and 20 ml and 1 g of active substance in glass bottles with a capacity of 30 ml (type 1 Eur.Pharm.) closed with a rubber stopper, crimped with an aluminum ring and a plastic cap. The AZ logo is painted on the outer surface of the bottle. 10 bottles with instructions for use in a cardboard box with first opening control.

Storage conditions
Store at a temperature not exceeding 30 C. Keep out of the reach of children.

Best before date
4 years. Do not use after the expiration date stated on the packaging.

Conditions for dispensing from pharmacies
On prescription.

Name and address of the legal entity in whose name the registration certificate was issued
AstraZeneca UK Limited, 2 Kingdom Street, London W2 6BD, UK
AstraZeneca UK Limited, 2 Kingdom Street, London W2 6BD, United Kingdom

Manufacturer
Dainippon Sumitomo Pharmaceuticals Company Co.,Ltd.
Tsurusaki 2200, Oita City, Oita, 870-0106, Japan
Dainippon Sumitomo Pharmaceuticals Company Ltd,
Tsurusaki 2200, Oita City, Oita, 870-0106, Japan
2. ACS Dobfar SpA, Viale Addetta 4/12, Tribiano, Milan, 20067, Italy
ACS Dobfar Spa, Viale Addetta 4/12, Tribiano, Milan, 20067, Italy

Issue quality control
AstraZeneca UK Limited, Silk Road Business Park, Macclesfield, Cheshire SK 10 2NA, UK
AstraZeneca UK Limited, Silk Road Business Park Macclesfield Cheshire SK 10 2NA, United Kingdom