Meronem
Meronem: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. For violations of liver function
- 11. Use in the elderly
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Meronem
ATX code: J01DH02
Active ingredient: meropenem (meropenem)
Producer: Dainippon Sumitomo Pharmaceuticals Company (Japan), ACS Dobfar (Italy), Astra Zeneca UK Ltd. (United Kingdom)
Description and photo update: 2019-14-08
Prices in pharmacies: from 6779 rubles.
Buy
Meronem is a broad-spectrum antibacterial drug.
Release form and composition
Meronem is produced in the form of a powder for the preparation of a solution for intravenous (i / v) administration: from white to light yellow (500 mg each in glass vials with a capacity of 10 and 20 ml, 10 vials in cardboard boxes with the first opening control; 1000 each) mg in glass vials with a capacity of 30 ml, 10 vials in cardboard packs with first opening control).
Active ingredient: meropenem trihydrate, in 1 bottle in terms of anhydrous meropenem - 500 or 1000 mg.
Auxiliary component: anhydrous sodium carbonate.
Pharmacological properties
Pharmacodynamics
Meropenem is an antibiotic belonging to the carbapenem class. It is used parenterally and is characterized by relative resistance to dehydropeptidase-1 (DHP-1). When using it, there is no need for additional administration of a DHP-1 inhibitor.
The bactericidal effect of meropenem is explained by its effect on the synthesis of the bacterial cell wall. The increased bactericidal activity of this substance against a wide range of anaerobic and aerobic microorganisms is due to the high ability of meropenem to penetrate the wall of bacterial cells, the high degree of stability of the active component of Meronem to most β-lactamases, and significant affinity for various penicillin-binding proteins (PSPs). Minimum bactericidal concentrations (MBCs) generally correspond to minimum inhibitory concentrations (MICs). For 76% of the bacterial species studied, the MBC / MIC ratio was 2 or less.
In vitro studies prove that meropenem has a synergistic effect against various antibiotics. Numerous in vitro and in vivo tests have confirmed the presence of a postantibiotic effect in this substance. Microorganisms are characterized by one or more of the following mechanisms of resistance to meropenem: the production of beta-lactamases that promote the hydrolysis of carbapenems, impaired permeability of the cell walls of gram-negative bacteria due to the synthesis of porins, intensification of efflux mechanisms, and a decrease in affinity for target PSBs. As criteria for susceptibility to meropenem, based on the pharmacokinetics of Meronem and on the correlation of microbiological and clinical data, only the MIC and zone diameter are recommended, which are determined individually for the respective pathogens.
Microorganisms with a zone diameter of more than 14 mm are considered susceptible to meropenem, intermediate sensitivity of bacteria to Meronem is observed with a zone diameter of 12–13 mm, and microorganisms with a zone diameter of 11 mm or less are resistant to Meronem.
The European Union has adopted the following MIC thresholds for meropenem for various pathogenic bacteria in a clinical setting:
- sensitivity ≤ 2 mg / l, resistance> 8 mg / l: Enterobacteriaceae, Acinetobacter, Pseudomonas, gram-positive and gram-negative anaerobes;
- sensitivity ≤ 2 mg / l, resistance> 2 mg / l: Streptococcus groups A, B, C, G, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae;
- sensitivity 2 mg / l: other streptococci;
- sensitivity ≤ 0.25 mg / l, resistance> 0.25 mg / l: Neisseria meningitidis.
Strains for which the MIC turns out to be above the sensitivity threshold are extremely rare or not detected at present. Detection of such a strain requires a repeat MIC test. If the result is confirmed, the strain is transferred to a reference laboratory, where it is considered resistant until a fully confirmed clinical effect concerning it is obtained.
The susceptibility to meropenem is determined using standard methods and the test results are interpreted according to local guidelines. The effectiveness of Meronem against a particular pathogen is confirmed by guidelines for antibiotic therapy and clinical experience.
The following microorganisms are considered susceptible to meropenem:
- gram-negative anaerobes: Prevotella disiens, Prevotella bivia, Bacteroides caccae, Bacteroides fragilis;
- gram-positive anaerobes: genus Peptostreptococcus (including magnus, P. anaerobius, P. micros), Peptoniphilus asaccharolyticus, Clostridium perfringens;
- gram-negative aerobes: Serratia marcescens, Citrobacter koseri, Citrobacter freundii, Proteus vulgaris, Proteus mirabilis, Enterobacter cloacae, Enterobacter aerogenes, Neisseria meningitidis, Escherichia coli, Morganella morganii, Klebsiella influencailia o, Klebsiella influenza o, Klebs
- gram-positive aerobes: Streptococcus pyogenes group A, Streptococcus agalactiae group B, Streptococcus pneumoniae, Streptococcus milleri group (S. intermedius, S. constellatus, S. anginosus), Enterococcus faecalis, Staphylococcus family, Staphylococcus (methicillin-sensitive) methicillin-sensitive strain).
For the following pathogenic microorganisms, the problem of acquired resistance is urgent:
- gram-negative aerobes: Pseudomonas aeruginosa, Burkholderia cepacia, genus Acinetobacter;
- gram-positive aerobes: Enterococcus faecium.
Bacteria that are naturally resistant to meropenem include:
- gram-negative aerobes: Legionella spp., Stenotrophomonas maltophilia;
- other pathogens: Mycoplasma pneumoniae, Chlamydophila psittaci, Chlamydophila pneumoniae, Coxiella burnetii.
Pharmacokinetics
Intravenous administration of meropenem over 30 minutes to healthy volunteers causes its maximum plasma concentration to be approximately 11 μg / ml at a dose of 250 mg, 23 μg / ml at a dose of 500 mg and 49 μg / ml at a dose of 1000 mg. However, with regard to the maximum concentration and the area under the concentration-time pharmacokinetic curve (AUC), there is no absolute proportional pharmacokinetic dependence on the administered dose of Meronem. There is a decrease in plasma clearance from 287 to 205 ml / min in the dose range of 250-2000 mg.
With an intravenous bolus injection of Meronem to healthy volunteers for 5 minutes, the maximum plasma concentration of the drug is 52 μg / ml at a dose of 500 mg and 112 μg / ml at a dose of 1000 mg. 6 hours after intravenous administration of meropenem at a dose of 500 mg, its content in blood plasma decreases to a value of 1 μg / ml or less. Prolonged (up to 3 hours or more) infusion of carbapenems can cause optimization of their pharmacodynamic and pharmacokinetic parameters. With a standard infusion for 30 minutes in healthy volunteers, two doses of 500 and 2000 mg every 8 hours, the ratio between the time period when the blood level of meropenem exceeds the MIC and the dosing interval (MIC is 4 μg / ml) is 30% and 58, respectively. %. The introduction of the same doses to volunteers through a three-hour infusion every 8 hours leads to an increase in this indicator to 43% and 73% at doses of 500 mg and 2000 mg, respectively. The mean plasma concentration of meropenem in healthy volunteers after an intravenous bolus infusion of Meronem for 10 minutes at a dose of 1000 mg exceeds the MIC of 4 μg / ml for 42% of the dosing interval, as opposed to 59% with a three-hour intravenous bolus of 1000 mg of meropenem.
The active component of Meronem penetrates well into most tissues and body fluids, including cerebrospinal fluid in patients with bacterial meningitis. At the same time, its concentrations exceed those required to suppress the vital activity of most microorganisms.
With repeated administration of Meronem with an interval of 8 hours in patients with normally functioning kidneys, no cumulation of meropenem is observed. In this category of patients, the half-life is approximately 1 hour. Meropenem binds to plasma proteins by 2%.
Approximately 70% of an intravenous dose of meropenem is excreted unchanged in the urine over a period of 12 hours, after which an insignificant renal excretion is noted. Concentrations of the active substance in the urine of more than 10 μg / ml remain unchanged for 5 hours after administration of the drug at a dose of 500 mg. With a treatment regimen that provides for the administration of meropenem, 500 mg every 8 hours or 1000 mg every 6 hours, no accumulation of the drug in urine and blood plasma is observed in volunteers with a normally functioning liver.
Meropenem forms the only metabolite without microbiological activity. According to studies in which children were participants, the pharmacokinetics of meropenem in adult patients and in children is almost the same. The half-life of the drug in children under 2 years of age is about 1.5–2.3 hours, and in the dose range of 10–40 mg / kg there is a linear dependence of this parameter on the dose.
Experiments on the study of the pharmacokinetics of Meronem in patients with renal insufficiency confirmed the correlation between the clearance of meropenem and the clearance of creatinine. When treating such patients, dose adjustment is necessary.
Pharmacokinetic studies in elderly people confirm a decrease in the clearance of the active component of Meronem, which correlates with a decrease in creatinine clearance due to age. Withdrawal of meropenem during hemodialysis leads to an increase in clearance of about 4 times compared with its clearance in patients with anuria.
According to pharmacokinetic studies, in which patients with liver dysfunctions participated, these pathological changes do not affect the pharmacokinetic parameters of meropenem.
Indications for use
For adults and children over 3 months old, Meronem is prescribed for the treatment of infectious and inflammatory diseases (as a monopreparation or in combination with other antimicrobial agents):
- Abdominal infections
- Urinary tract infections;
- Infectious and inflammatory diseases of the pelvic organs, including endometritis;
- Septicemia;
- Meningitis;
- Infections of the skin and its structures.
As a monopreparation or in combination with antifungal / antiviral agents, Meronem is prescribed for empiric therapy in adults with suspected infection accompanied by symptoms of febrile neutropenia.
Contraindications
Absolute:
- Children up to age 3 months;
- Severe hypersensitivity (severe skin or anaphylactic reactions) to any antibacterial drug with a beta-lactam structure, i.e. to cephalosporins and / or penicillins;
- A history of hypersensitivity to meropenem or other drugs from the carbapenem group.
Relative (special care must be taken due to the risk of complications):
- The presence of complaints from the gastrointestinal tract (for example, diarrhea), especially in patients with colitis;
- Concomitant use of potentially nephrotoxic drugs.
During pregnancy / lactation, Meronem can be prescribed only if the expected benefit from therapy outweighs the possible risks to the fetus / child
Instructions for the use of Meronem: method and dosage
Meronem is given intravenously as a bolus injection over at least 5 minutes or as an infusion over 15-30 minutes.
For bolus intravenous injections, Meronem is diluted with sterile injection water (for 250 mg of meropenem - 5 ml of water)
For intravenous infusion, Meronem is diluted with one of the following infusion fluids (in an amount of 50-200 ml): 5 or 10% dextrose solution, 2.5 or 10% mannitol solution, 0.9% sodium chloride solution, 5% dextrose solution with 0.225% sodium chloride solution, 5% dextrose solution with 0.9% sodium chloride solution, 5% dextrose solution with 0.02% sodium bicarbonate solution, 5% dextrose solution with 0.15% potassium chloride solution.
When diluting, the standard aseptic rules should be followed, before administration - shake the diluted solution. Meronem should not be rushed or added to other medications. All vials are for single use.
Doses and duration of treatment are set individually, depending on the type of pathogen, the severity of the disease and the general condition of the patient.
Recommended doses for adults:
- Pneumonia, gynecological infections, infections of the urinary tract, skin and its structures: 500 mg intravenously every 8 hours;
- Peritonitis, septicemia, nosocomial pneumonia, suspected bacterial infection in patients with symptoms of neutropenia: 1000 mg intravenously every 8 hours;
- Meningitis: 2000 mg every 8 hours.
Recommended doses for adult patients with impaired renal function, depending on creatinine clearance (CC):
- CC 26-50: 1 dose every 12 hours;
- CC 10-25: ½ dose every 12 hours;
- CC less than 10: ½ dose every 24 hours.
The active substance Meronem is excreted during hemodialysis. For this reason, in the case of long-term treatment, in order to restore the effective concentration of meropenem in the blood plasma, it is recommended to administer the dose prescribed by the doctor at the end of the hemodialysis procedure.
There is no experience of using Meronem in the treatment of patients on peritoneal dialysis.
For children aged 3 months to 12 years, the drug is administered intravenously every 8 hours at a dose of 10-20 mg / kg, depending on the condition of the child, the type of infection, the sensitivity of the pathogen and the severity of the disease.
Children weighing more than 50 kg are prescribed doses for adults.
The recommended dose for meningitis is 40 mg per kilogram of body weight every 8 hours.
There is no experience of using Meronem in children with impaired renal and liver function.
Side effects
In general, Meronem is well tolerated by patients, side effects rarely require discontinuation of therapy.
Possible adverse reactions:
- Hematopoietic system: often - thrombocytosis; infrequently - thrombocytopenia, eosinophilia; rarely - agranulocytosis, neutropenia, leukopenia; very rarely - hemolytic anemia;
- Gastrointestinal tract: often - increased activity of hepatic transaminases, diarrhea, nausea and / or vomiting, increased serum bilirubin, alkaline phosphatase and lactate dehydrogenase; infrequently - constipation * and cholestatic hepatitis *; very rarely - pseudomembranous colitis;
- Nervous system: infrequently - paresthesia, headache, insomnia *, increased excitability *, anxiety *, fainting *, depression *, hallucinations *; rarely - convulsions;
- Immune system: very rarely - manifestations of anaphylaxis, angioedema;
- Cardiovascular system: infrequently - thromboembolism of the branches of the pulmonary artery *, bradycardia *, tachycardia *, decrease or increase in blood pressure *, heart failure *, myocardial infarction *, cardiac arrest *;
- Kidneys and urinary system: infrequently - an increase in the concentration of urea and creatinine in the blood;
- Skin and subcutaneous tissue: infrequently - itchy skin, rash and urticaria; very rarely - Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis;
- Respiratory system: infrequently - dyspnea *;
- Others: often - local reactions (pain, inflammation, thrombophlebitis at the injection site of Meronem); rarely - oral mucosa candidiasis, vaginal candidiasis.
* The causal relationship of these side effects with the use of Meronem has not been established.
Overdose
During treatment with Meronem, an accidental overdose is possible, especially in patients with renal dysfunction. In this case, symptomatic therapy is prescribed. In a normal state, the drug is rapidly excreted through the kidneys. In patients with renal dysfunction, meropenem and its metabolite are effectively eliminated from the body by hemodialysis.
special instructions
There is no experience with the use of Meronem in children with primary / secondary immunodeficiency and neutropenia.
Treatment of patients with liver disease should be carried out under careful monitoring of the concentration of bilirubin and the activity of transaminases.
Due to the likelihood of overgrowth of insensitive microorganisms during therapy, it is necessary to monitor the patient's condition.
When using Meronem as a monopreparation in the treatment of critically ill patients with diagnosed or suspected lower respiratory tract infection caused by Pseudomonas aeruginosa, it is recommended to regularly conduct sensitivity tests.
In rare cases, Meronem contributes to the development of pseudomembranous colitis, which can vary in severity from mild to life-threatening. It is important to remember about the risk of pseudomembranous colitis when diarrhea occurs while taking the drug.
The likelihood of developing cross-allergic reactions between Meronem and cephalosporins, penicillins, beta-lactam antibiotics should be taken into account. There are reports of rare cases of development of serious hypersensitivity reactions to meropenem, including with a fatal outcome. For this reason, before prescribing this drug, it is necessary to collect a thorough history of the patient, paying particular attention to hypersensitivity reactions to beta-lactam antibacterial agents. If such data are available in the medical history, Meronem is used with extreme caution, if an allergic reaction occurs, Meronem is canceled and appropriate measures are taken.
Meronem is not recommended for use in infectious diseases caused by methicillin-resistant staphylococcus.
The effect of the drug on the speed of reactions of a person and his ability to concentrate has not been studied. However, one should take into account the likelihood of developing side effects such as paresthesia, headache, convulsions.
Application during pregnancy and lactation
The safety of using Meronem in pregnant women is not well understood. Animal experiments have shown no adverse effects on the developing fetus. Meronem should not be used during pregnancy, unless the potential benefits of treatment for the mother are significantly higher than the likely risks for the fetus. In all cases, the drug is taken exclusively under the supervision of a specialist.
It is known that meropenem is excreted in breast milk. The drug is not prescribed during breastfeeding. However, if treatment during lactation is necessary for vital reasons for the mother, either Meronem should be canceled or breastfeeding should be abandoned.
For violations of liver function
No dose adjustment is required in patients with hepatic impairment. The use of Meronem in patients with liver dysfunction should be accompanied by careful monitoring of the level of bilirubin and transaminases.
Use in the elderly
In elderly patients with normal renal function or with CC exceeding 50 ml / min, dose adjustment is not required.
Drug interactions
According to the instructions, Meronem is not recommended to be used simultaneously with valproic acid preparations.
Analogs
Meronem's analogs are: Meropenem, Meropenabol, Meropenem-Vexta, Meropenem Spencer, Meropenem Jodas, Meropenem-Vial, Meropenem-Vero, Propinem, Cyronem.
Terms and conditions of storage
Store at temperatures up to 30 ° C out of the reach of children. Do not freeze.
Shelf life is 4 years.
The diluted Meronem also retains its effectiveness for some time.
Solvent type: storage time in a refrigerator (4 ° C) / storage time at room temperature (15-25 ° C):
- Water for injection: 8 hours / 24 hours;
- 0.9% sodium chloride solution: 8 hours / 48 hours;
- 5% dextrose solution: 3 hours / 14 hours;
- 10% dextrose solution: 2 hours / 8 hours;
- 5% dextrose solution and 0.225% sodium chloride solution: 3 hours / 14 hours;
- 5% dextrose solution and 0.15% potassium chloride solution: 3 hours / 14 hours;
- 5% dextrose solution and 0.02% sodium bicarbonate solution: 2 hours / 8 hours;
- 5% dextrose solution and 0.9% sodium chloride solution: 3 hours / 14 hours;
- 2.5 or 10% mannitol solution: 3 hours / 14 hours.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Meronem
According to reviews, Meronem is an effective drug that has proven itself in the severe course of diseases such as surgical sepsis, out-of-hospital infections, peritonitis, pyelonephritis, accompanied by the development of urosepsis, and purulent meningitis. The drug is characterized by high bioavailability, a wide spectrum of action, minor side reactions and minimal resistance of microorganisms, therefore Meronem is often used in intensive care units and intensive care units.
There are reports that the drug has been successfully used in extremely severe cases of bacterial meningitis in newborns, when previously antibiotic therapy with aminoglycosides, fluoroquinolones or third generation cephalosporins did not give the desired result. There were also no toxic effects in children.
Many patients do not like the high cost of the drug, but its price for the entire course of treatment turns out to be significantly lower than the cost of the course of its analogue Tienam.
Price for Meronem in pharmacies
The approximate price for Meronem with a dosage of 500 mg is 5,082-8740 rubles, and with a dosage of 1000 mg - 11,879-15,290 rubles (the package includes 10 bottles).
Meronem: prices in online pharmacies
|
Drug name Price Pharmacy |
|
Meronem 0.5 g powder for solution for intravenous administration 10 pcs. RUB 6779 Buy |
|
Meronem 1 g powder for solution for intravenous administration 10 pcs. 8999 RUB Buy |
|
Meronem powder for preparation of solution for intravenous administration, bottle 1g 10pcs 12561 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
