Meronem, 0.5 g, powder for solution for intravenous administration, 10 pcs.

Pharmacological properties

Pharmacodynamics

Meronem is an antibiotic of the carbapenem group, which is intended for parenteral use; it is relatively resistant to human dehydropeptidase and does not require additional administration of an inhibitor. It has a bactericidal effect due to the fact that it affects the synthesis of the bacterial cell wall. The high level of bactericidal activity of meropenem against a wide range of anaerobic and aerobic bacteria is explained by its high ability to penetrate the bacterial cell wall, a high level of stability to many beta-lactamases and significant affinity for various pennicillin-binding proteins.

Bactericidal minimum concentrations are essentially the same as inhibitory minimum concentrations. For those 76% of bacterial species that were tested, the ratio of these two concentrations did not exceed 2.

In vitro tests show that meropenem acts synergistically with various antibiotics.

These tests also show that this substance has a post-antibiotic effect.

Microorganisms may have one or several mechanisms of resistance to meronem:

1. Products of beta-lactamases, under the influence of which carbapenems are hydrolyzed.
2. Decreased affinity for final PSBs.
3. Due to impaired porin synthesis, the permeability of the cell wall of Gram-negative bacteria may be impaired.

Meronem's analogs

Level 4 ATX code matches:
Invanz

Meropenem

Tienam

Meropenem , Meropenem , Meropenem-Vexta , Meropenem Spencer , Meropenem Jodas , Meropenem-Vial , Meropenem-Vero , Propinem , Cyronem . These analogs have the same release form and dosage.

Pathogens that are sensitive to meropenem

Aerobes are gram-positive

1. Streptococcus pyogenes group A.
2. Streptococcus pneumoniae.
3. Streptococcus milleri group.
4. Streptococcus agalactiae group B.
5. Genus Staphylococcus.
6. Staphylococcus aureus.
7. Enterococcus faecalis.

​Aerobes are gram-negative

1. Serratia marcescens.
2. Proteus vulgaris.
3. Proteus mirabilis.
4. Neisseria meningitidis.
5. Morganella morganii.
6. Klebsiella pneumoniae.
7. Klebsiella oxytoca.
8. Haemophilus influenzae.
9. Escherichia coli.
10. Enterobacter cloacae.
11. Enterobacter aerogenes.
12. Citrobacter koseri.
13. Citrobacter freudii.

Gram-positive anaerobes

1. Genus Peptostreptococcus.
2. Peptoniphilus asaccharolyticus.
3. Clostridium perfringens.

Gram-negative anaerobes

1. Prevotella disiens.
2. Prevotella bivia.
3. Bacteroides fragilis.
4. Bacteroides caccae.

​Pathogens for which the problem of acquired resistance is relevant

1. Gram-positive aerobes - Enterococcus faecium.
2. Gram-negative aerobes - Pseudomonas aeruginosa, Burkholderia cepacia, genus Acinetobacter.

Pathogens that have natural resistance

These include aerobes - Legionella spp, Stenotrophomonas maltophilia.

Other pathogens include: Coxiella burnetii, Chlamydophila psittaci, Chlamydophila pneumoniae, Mycoplasma pneumoniae.

Pharmacokinetics

Within 30 minutes, intravenous administration of the drug "Meronem" to a healthy person leads to a maximum concentration , which is approximately equal to:

1. For a dose of 250 milligrams - 11 mcg/ml.
2. For a dose of 500 milligrams - 23 mcg/ml.
3. For a dose of 1 gram - 49 mcg/ml.

After 6 hours after intravenous administration of 500 milligrams, the concentration of meropenem in the blood plasma decreases to 1 mcg/ml and below.

is excreted unchanged by the kidneys within 12 hours. After this, minor renal excretion can be determined.

In the urine, the concentration of meropenem, which exceeds 10 mcg/ml, is maintained for 5 hours after the administered dose of 500 mg. In volunteers with normal hepatic function, no accumulation was observed when a dose of 500 mg was administered every 8 hours or every 6 hours - 1 gram in the urine and in the blood plasma.

The only metabolite of meropenem is that it is microbiologically inactive.

In children, studies have shown that the pharmacokinetics of this drug are similar to those in adults.

In children under 2 years of age, the half-life of meropenem is approximately 90 to 140 minutes. A linear relationship is observed in the dose range from 10 to 40 mg/kg.

Renal failure

In patients with renal impairment, studies have shown that creatine clearance correlates with meropenem clearance. For such patients, the dose must be adjusted.

In elderly individuals, studies revealed a decrease in meropenem clearance, correlating with an age-related decrease in creatinine clearance. Meropenem is excreted with a clearance during hemodialysis that is approximately 4 times higher than the clearance of meropenem in people with anuria.

Liver failure

In patients suffering from liver disease, pharmacokinetic studies have shown that pathological changes do not affect the pharmacokinetics of meropenem.

Meronem analogues

Dosage form: powder for the preparation of solution for intravenous administration. Composition One bottle contains:

Meronem® 0.5 g Meronem® 1 g Active ingredient: meropenem trihydrate 570 mg 1140 mg equivalent to meropenem anhydrous 500 mg 1000 mg Excipient 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 corresponding 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 Staphylococcus genus (methicillin-sensitive), including Staphylococcus epidermidis Streptococcus agalactiae group B Group Streptococcus milleri (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 Morgan ella morganii Neisseria meningitidis Proteus mirabilis Proteus vulgaris Serratia marcescens Gram-positive anaerobes: Clostridium perfringens Peptoniphilus asaccharolyticus Genus Peptostreptococcus (including P. micros, Panaerobius, P. magnus) Gram-negative anaerobes: Bacteroides caccae Bacteroides fragilis Prevotella bivia Prevotella disiens Pathogens for which it is relevant on the problem of acquired resistance: 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 regard to the maximum concentration (Cmax) and the area under the concentration-time pharmacokinetic curve (AUC), there is no absolute pharmacokinetic proportional relationship 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® to healthy volunteers over 5 minutes resulted in a maximum plasma concentration of approximately 52 μg/ml for a dose of 500 mg and 112 mcg/ml - for a dose of 1 g. 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. Renal 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; - urinary system infections; - 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.

With caution Simultaneous 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®.

Method of administration and dosage Adults The dose and duration of therapy should be determined depending 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) - Administration frequency 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

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 impaired liver function There is no need for dosage adjustment in patients with hepatic impairment (see section "Special Instructions"). Elderly patients Elderly patients with normal renal function or creatinine clearance more than 50 ml/min do not require dose adjustment. 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, 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 administrationMeronem® 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 effects 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); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); unspecified frequency (frequency cannot be determined from available data). 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, fainting**, hallucinations**, depression**, anxiety **, increased excitability**, insomnia** Rarely: convulsions Gastrointestinal tract Common: nausea, vomiting, diarrhea, increased activity of liver transaminases, alkaline phosphatase, lactate dehydrogenase and serum bilirubin concentration 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) Immune system Very rare: angioedema, manifestations of anaphylaxis Cardiovascular system Uncommon: heart failure**, cardiac arrest**, tachycardia**, bradycardia**, myocardial infarction**, decrease or increase in blood pressure (BP)**, branch thromboembolism pulmonary artery** Kidneys and urinary tract Uncommon: increased creatinine concentration in the blood, increased urea concentration in the blood Respiratory tract Uncommon: dyspnea** Other Common: local reactions - inflammation, thrombophlebitis, pain at the injection site Rare: vaginal candidiasis and candidiasis of the mucous membrane oral cavity *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.

Interactions 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.

Effect 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 a 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 Euro .Farm.) 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.

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

Conditions for dispensing from pharmacies By prescription.

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

Manufacturer Dainippon Sumitomo Pharmaceuticals Company 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

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

Meronem - instructions for use

Meronem is intended for the treatment of inflammatory and infectious diseases in adults and children (over 3 months of age) that were caused by pathogens sensitive to meropenem:

1. Septicemia.
2. Meningitis.
3. Infections of the skin and its structure.
4. Endometritis.
5. Abdominal infections.
6. Infections of the urinary system.
7. Pneumonia and nosocomial pneumonia.

Empirical treatment of older patients with suspected infection with symptoms of febrile neuropenia in monotherapy or in combination with antifungal or antiviral drugs.

The effectiveness of this drug has been proven in all cases.

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.

Experienced experts recommend adhering to the following rules for taking Meronem:

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 medicine, 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. 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.

Contraindications for use

Meronem is contraindicated in people with a history of hypersensitivity to meropenem or other medications of the carbapenem group.

In case of severe hypersensitivity (severe skin reactions and anaphylactic reactions) to any antibacterial agent that has a beta-lactam structure (to cephalosporins and penicillins). This antibiotic is also contraindicated for children under three months.

Caution should be used concomitantly with potentially nephrotoxic substances. And also for people with complaints about the gastrointestinal tract (diarrhea), and especially those who suffer from colitis.

Indications

Meronem is recommended for use in children and adults for the treatment of the following infectious diseases caused by one or more pathogens sensitive to the drug:

• Pneumonia (including hospital-acquired).
• Abdominal infections.
• Urinary system infections.
• Infectious and inflammatory lesions of the pelvic organs (such as endometritis).
• Infections of the skin and its structures.
• Septicemia.
• Meningitis.

The drug is used in the empirical treatment of adult patients, both as monotherapy and in combination with antiviral or antifungal drugs for suspected infection with symptoms of febrile neutropenia. The effectiveness of the drug has also been proven in combination with other antimicrobial drugs and in monotherapy in the treatment of polymicrobial infections.

Use during pregnancy and breastfeeding

During pregnancy, the safety of using the drug "Meronem" has not been studied. And those studies that were conducted on pregnant animals did not show any adverse effects on the developing fetus.

During pregnancy , Meronem should not be used by women. The exception is those cases when the potential benefit for the mother from its use exceeds the possible risk to the fetus. In each case, the medication must be taken under strict medical supervision.

During breastfeeding, it has been observed that meropenem is excreted in breast milk. That is why you should not take Meronem during breastfeeding.

The only exception is when the potential benefit for the mother from using the substance outweighs the possible risk for the baby. When assessing the risk to the mother, it is worth making a decision to stop breastfeeding or discontinue the use of Meronem.

Contraindications

Meronem is contraindicated for use in case of hypersensitivity to the active (meropenem) or auxiliary components of the drug.

The antibiotic Meronem can be used for all age groups with the exception of children under three months.

During pregnancy, the medication is prescribed only according to strict indications, taking into account the possible adverse effects of Meronem on the fetus.

It is also not recommended to use Meronem during breastfeeding, since its safety for the baby has not been clinically proven.

Directions for use and dosage

In adults

The duration and dosage of therapy used are determined depending on the patient's condition, as well as the severity and type of infection. The following daily dosages :

1. For the treatment of skin structures and infections, endometritis, urinary tract infections, pneumonia, 500 milligrams intravenously are prescribed every 8 hours.
2. For the treatment of septicemia, if a bacterial infection is suspected in patients with symptoms of neutropenia, for the treatment of peritonitis, nosocomial pneumonia, 1 gram is prescribed intravenously every 8 hours.
3. For the treatment of meningitis, it is recommended to use 2 grams intravenously every 8 hours. This dosage of use has not been studied enough.

Dosage for adults with renal impairment

For people with creatinine clearance less than 51 ml/min, the dosage should be reduced as follows:

1. With a creatinine clearance of 26–50 ml/min, 1 gram should be administered every 12 hours.
2. With a clearance of 10–25, 500 milligrams should be administered every 12 hours.
3. If creatinine clearance is less than 10, 500 milligrams should be administered every 24 hours.

is excreted during hemofiltration and hemodialysis. If treatment with Meronem requires a long period of use, it is recommended to administer it at the end of the hemodialysis procedure. This is necessary to restore effective plasma concentrations.

There are currently no data available for use in patients undergoing peritoneal dialysis.

Dosage for adults with impaired liver function

For such patients, there is no need to adjust the dosage.

Dosage for elderly patients

If an elderly person does not suffer from kidney or liver diseases, then the dosage should not be adjusted.

Dosage for children

For children aged from three months to 12 years, the recommended dosage for intravenous administration is 10-20 mg/kg. The dose must be administered every 8 hours depending on the severity and type of infection, the patient's condition and the sensitivity of the pathogenic microorganism. For children whose body weight exceeds 50 kilograms, the dosage for adults is used. When treating meningitis, the drug must be administered every 8 hours. The required dosage in this case is 40 mg/kg. This dosage has not been studied enough. Also, experiments were not conducted on children with impaired kidney and liver function.

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 or 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 medicine during lactation is not recommended.

Method of administration

"Meronem" for intravenous use can be introduced into the human body as a bolus intravenous injection over a period of at least 5 minutes. Another method of administration is intravenous infusion over 15 to 30 minutes. In order to dilute this drug, it is necessary to use appropriate infusion fluids.

In order to prepare a solution for bolus intravenous injection, you need to dilute the drug in special sterile water (5 milliliters of water for 250 milligrams of meropenem). The concentration of the solution should be 50 mg/ml. This solution remains stable at a temperature of 25 degrees for three hours. And when stored in the refrigerator (temperature range from 2 to 8 degrees) - for 16 hours.

In order to prepare a solution for intravenous infusion, you need to dissolve the drug with sodium chloride solution (0.9%) for infusion or with a 5% glucose solution (dextrose). The concentration of the solution should be from 1 to 20 mg/ml.

Such a solution at a temperature of 25 degrees remains stable for 3 hours, and at a temperature of 2 – 8 degrees, then for 24 hours, if a sodium chloride solution (0.9%) was used to prepare it.

If a 5% glucose solution was used for preparation, then the injection should be used immediately.

It is forbidden to freeze the Meromene solution.

Prescription in childhood

• In children aged from 3 months to 12 years, the drug is usually administered intravenously in a dosage of no more than 20 mg per 1 kg of body weight. Doses will be calculated depending on the condition of the small patient, the sensitivity of the pathogen, the type of infection, as well as the severity of the clinical picture.
• For children weighing more than 50 kg, Meronem is prescribed in an adult dosage.

Side effects

In rare cases, the following severe side effects :

1. Allergic reactions: anaphylactic reactions and angioedema have been observed very rarely.
2. Dermatological reactions: in rare cases - epidermal toxic necrolysis, Stevens-Johnson syndrome, erythema multiforme (exudative); more often - urticaria, rash, itching.
3. Digestive system: very rarely - colitis , LHD and alkaline phosphatase in combination or separately, transaminases, reversible increase in the level of bilirubin in the blood; more often - diarrhea, vomiting, nausea, abdominal pain.
4. Bleeding system: neutropenia and leukopenia, thrombocytopenia, zosinophilia, reversible thrombocytosis. In rare cases, a positive indirect or direct Coombs test was observed; Very rarely, a decrease in partial thromboplastin time was observed.
5. Central and peripheral nervous system: paresthesia, headache.
6. Local reactions: pain at the injection site, thrombophlebitis, inflammation.
7. Effects that are caused by biological effects: vaginal and oral candidiasis.

Side effects

In general, Meronem is well tolerated by patients; side effects rarely require discontinuation of therapy. Possible adverse reactions:

• hematopoietic system: often – thrombocytosis; uncommon – thrombocytopenia, eosinophilia;
• rarely – agranulocytosis, neutropenia, leukopenia; very rarely - hemolytic anemia;
• gastrointestinal tract: often - increased activity of liver transaminases, diarrhea, nausea and/or vomiting, increased concentrations of serum bilirubin, alkaline phosphatase and lactate dehydrogenase; uncommon – constipation and cholestatic hepatitis; very rarely - pseudomembranous colitis;
• nervous system: uncommon – paresthesia, headache, insomnia, increased excitability, anxiety, fainting, depression, hallucinations; rarely – convulsions;
• immune system: very rarely - manifestations of anaphylaxis, angioedema;
• cardiovascular system: uncommon - thromboembolism of the branches of the pulmonary artery, bradycardia, tachycardia, decreased or increased blood pressure, heart failure, myocardial infarction*, cardiac arrest;
• kidneys and urinary system: infrequently - increased concentrations of urea and creatinine in the blood;
• skin and subcutaneous tissue: uncommon – itching, rash and urticaria; very rarely - Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis;
• respiratory system: infrequently – dyspnea;
• other: often - local reactions (pain, inflammation, thrombophlebitis at the site of meronem administration);
• rarely – candidiasis of the oral mucosa, vaginal candidiasis.

The cause-and-effect relationship of these side effects with the use of Meronem has not been established.

special instructions

In pediatric practice, there is no experience with the use of the drug in patients with primary or secondary immunodeficiency and neutropenia.

Regular sensitivity testing is recommended if a lower respiratory tract infection is suspected or already detected. This applies to patients who are in critical condition and meropenem is used as monotherapy.

Very rarely, when taking this drug, the development of pseudomembranous colitis is observed. Its forms of manifestation can range from mild to those that are life-threatening. It is necessary to remember about the possible development of pseudomembranous colitis if diarrhea occurs, which appeared during the use of this drug.

If pseudomembranous colitis appears, then you should abandon this type of antibiotic.

The use of medications that inhibit intestinal motility is contraindicated.

People with a low seizure threshold should be especially careful when taking this medication. This is due to the fact that cases of seizures have been identified.

Allergic reactions occur when using carbapenems and cephalosporins, penicillins and beta-lactams.

In some cases, patients complained of hypersensitivity from the drug. Therefore, before prescribing this type of antibiotic to you, the doctor should find out in detail your history of hypersensitivity to beta-lactam antibiotics. If you are allergic to this antibiotic, you should immediately stop administering it and take appropriate treatment measures.

The use of the drug in patients with impaired liver function is carried out under special monitoring of bilirubin levels and transaminase activity.

Side effects

The use of Meronem may cause the following side effects:

• Central and peripheral nervous system: paresthesia, headache, hallucinations, fainting, anxiety, depression, insomnia, increased excitability; rarely - convulsions.
• Digestive system: nausea, vomiting, abdominal pain, diarrhea, constipation; in some cases - increased levels of bilirubin in the blood, alkaline phosphatase and LDH in combination or separately, increased activity of liver enzymes, cholestatic hepatitis, pseudomembranous colitis (in some cases).
• Cardiovascular system: uncommon - increase or decrease in blood pressure, bradycardia, tachycardia, heart failure, myocardial infarction, cardiac arrest, thromboembolism of the branches of the pulmonary artery.
• Urinary tract and kidneys: uncommon - increased concentrations of creatinine and urea in the blood.
• Hematopoietic system: eosinophilia, reversible thrombocytosis, thrombocytopenia, neutropenia and leukopenia (including agranulocytosis). In some patients, a positive indirect or direct Coombs test is possible.
• Respiratory tract: dyspnea.
• Allergic manifestations: rarely - anaphylactic reactions, angioedema.
• Dermatological reactions: urticaria, itching, rash; rarely – Stevens-Johnson syndrome, erythema multiforme (exudative) and toxic epidermal necrolysis.
• Local reactions: pain at the injection site, thrombophlebitis, inflammation.
• Effects due to biological effects: vaginal candidiasis, candidiasis of the oral mucosa.

Interaction with other medications

Probenecid competes with meropenem for active tubular secretion, thereby inhibiting the renal excretion of meropenem. This causes an increase in the half-life of the substance and its concentration in the blood plasma. Due to the fact that the duration of action and effectiveness of Meronem without probenecid are adequate, it is not recommended to administer them together.

The possible effect of Meronem and other drugs on metabolism and protein binding has not been studied. But taking into account the fact that the level of binding of blood plasma proteins and meropenem is very low, Meronem should not be combined with other medications.

Meronem can reduce the amount of valproic acid in the blood serum. In some people, levels may drop below therapeutic levels.

Reviews

According to reviews from most patients, this is an effective drug that was used for severe diseases (community-acquired infections, pyelonephritis with the development of urosepsis , purulent meningitis , peritonitis , surgical sepsis ). It has a very broad spectrum of action, high bioavailability, minimal microbial resistance and minimal side effects. That is why Meronem is very often used in the intensive care unit.

Thus, the experience of using Meronem in severe cases of bacterial meningitis in newborns , when previously carried out antibacterial therapy (third generation cephalosporins, fluoroquinolones and aminoglycosides ) was ineffective. toxic effects were recorded in children .

Many patients are not satisfied with its cost. But, if you calculate the exchange rate cost of treatment with this drug, it is significantly lower than Tienam .

Release form, storage conditions and release from pharmacies

According to the release form, “Meronem” is a powder for the preparation of an intravenous solution of 500 milligrams and 1 gram. A glass bottle of 500 milligrams of the active substance contains 10 and 20 milliliters, and 1 gram contains 30 milliliters. The bottles are closed with rubber caps, which are crimped on top with an aluminum ring and a plastic cap. The AZ logo is painted on the outside of the bottle. The bottles are packed in a cardboard box of 10 pieces. They come with instructions, and after that the box is sealed with tamper evident tape.

Meronem must be stored in places inaccessible . The air temperature in the room where the drug is stored should not exceed 30 degrees.

Shelf life: 48 months. After the expiration date, which the manufacturer indicated on the packaging as the end date of use, the drug should be disposed of. Its use after this date is strictly prohibited.

Meronem is sold from pharmacies only with a prescription issued by the attending physician.

Meronem release form

The antibiotic Meronem is produced in the form of a powder for the preparation of an infusion solution in bottles containing the active component (meropenem) in quantities of 0.5 and 1 g, 10 bottles per package.

Analogues of Meronem are medicines:

• By active substance - Merexid, Jenem, Meropenem, Cyronem, Propinem, Meropenem-Vero;
• According to the therapeutic effect they provide and belonging to the same pharmacological group - Tsilapenem, Grimipenem, Doriprex, Invanz, Tienam, Tsilapenem.

Meronem price, where to buy

You can buy it in pharmacies in Moscow and other cities. The price of Meronem depends on the dose. The cost of the drug 1 g in bottle No. 10 ranges from 12,880 rubles. up to 15,560 rubles, and 0.5 g in bottle No. 10 from 8,022 rubles. up to 8845 rub.

• Online pharmacies in UkraineUkraine

Pharmacy24

• Meronem 500 mg No. 10 lyophilized powder for solution for injection ECS Dobfar S.p.A., Italy/AstraZeneca UK Limited, Great Britain
  3458 UAH.order