Meropenem-Vekst - instructions for use, dose, side effects, contraindications

has bactericidal action (suppresses cell wall synthesis bacteria), easily penetrates the bacterial cell wall, is resistant to the action of most beta-lactamases.

Unlike imipenem, it practically does not break down in the renal tubules with dehydropeptidase-1 (it does not need to be combined with cilastatin-specificinhibitor dehydropeptidase-1) and, accordingly, does not form nephrotoxic degradation products, has a high affinity for proteins that bind penicillin.

Bactericidal and bacteriostatic concentrations are different.

Interacts with receptors - specific penicillin-binding proteins on the surface of the cytoplasmic membrane, inhibits the synthesis of the peptidoglycan layer of the cell wall, suppresses transpeptidase, promotes the release of autolytic enzymes of the cell wall, which eventually causes its damage and the death of bacteria.

The spectrum of antibacterial activity of meropenem in vitro includes the majority of clinically significant Gram-positive and Gram-negative aerobic and anaerobic strains of bacteria, namely:

Gram-positive aerobes

Enterococcus faecalis (with the exception of vancomycin-resistant strains), Staphylococcus aureus (penicillinase-inducing and penicillinase-producing [methicillin-sensitive]); Streptococcus agalactiae, Streptococcus pneumoniae (only penicillin-sensitive); Streptococcus pyogenes, Streptococcus spp. group of viridans.

Gram-negative aerobes:

Escherichia coli, Haemophilus influenzae (penicillinase-inducing and penicillinase-producing), Klebsiella pneumoniae, Neisseria meningitidis, Pseudomonas aeruginosa, Proteus mirabilis.

Anaerobic bacteria:

Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus spp.

Meropenem is effective in vitro with respect to the microorganisms listed below, however, its clinical effectiveness in diseases caused by these pathogens has not been proven:

Gram-positive aerobes:

Staphylococcus epidermidis (penicillinase-inducing and penicillinase-producing [methicillin-sensitive]).

Gram-negative aerobes:

Acinetobacter spp., Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diyersus, Citrobacter jreundii, Enterobacter cloacae; Haemophilus influenzae (ampicillin-resistant, penicillinase-sparing strains), Hajhia alvei, .Klebsiella oxytoca, Moraxella catarrhalis (penicillinase-inducing and penicillinase-producing), Morganella morganii, Pasteurella multocida, Proteus vulgaris, Salmonella spp., Serratia marcescens, Shigella spp., Yersinia enterocolitica.

Anaerobic bacteria:

Bacteroides distasonis, Bacteroides ovatus, Bacteroides uniformis, Bacteroides ureolyticus, Bacteroides vulgatus, Clostridium difficile, Clostridium perfringens, Eubacterium lentum, Fusobacterium spp., Prevotella bivia, Prevotella intermedia, Prevotella melaninogenica, Porphyromonas asaccharolytica, Propionibacterium acnes.

Pharmacokinetics:

When intravenously administered (IV) 250 mg for 30 minutes, the maximum concentration in the blood plasma (Cm11 μg / ml, for a dose of 500 mg - 23 μg / ml, 1000 mg - 49 μg / ml (absolute pharmacokinetic proportional dependence on the administered dose for Cmax and AUC (the area under the pharmacokinetic curve "concentration-time") is not). When the dose is increased from 250 to 2000 mg, the clearance decreases from 287 to 205 ml / min. With intravenous bolus administration for 5 min, 500 mg of C max is 52 μg / ml, 1000 mg is 112 μg / ml. Connection with plasma proteins - 2%.

It penetrates well into most tissues and body fluids, including the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations exceeding those required for the suppression of most bacteria (bactericidal concentrations are created 0.5-1.5 hours after the start of infusion). In small amounts penetrates into breast milk.

Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite. The half-life period (T1 / 2) is 1 hour, in children under 2 years it is 1.5-2.3 hours. In the dose range of 10-40 mg / kg yadults and children there is a linear dependence of pharmacokinetic parameters. Do not cumulate.

It is excreted by the kidneys - 70% unchanged for 12 hours. The concentration of meropenem in the urine, exceeding 10 μg / ml, is maintained for 5 hours after the administration of 500 mg. In patients with renal insufficiency, the clearance of meropenem correlates with creatinine clearance (CC). In elderly patients, a decrease in meropenem clearance correlates with a decrease in QC associated with age. T1 / 2 - 5 hours. hemodialysis.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation,including in cases of polymicrobial infections (as, monotherapy or combination with other antibacterial, antiviral and antifungal drugs):

- Lower respiratory tract infections (including pneumonia, including the hospital);

- intra-abdominal infections (including complicated appendicitis, peritonitis, pelvioperitonitis);

- infection of the urinary system (including pyelonephritis, pyelitis);

- infections of the skin and soft tissues (including erysipelas, impetigo, secondarily infected dermatoses);

- infections of the pelvic organs (including endometritis);

- bacterial meningitis;

- empirical treatment (in, monotherapy or in combination with antiviral or antifungal drugs) if suspected, for infection in adult patients with febrile episodes with neutropenia.

Contraindications:

Hypersensitivity to any of the components of the drug, expressed Hypersensitivity (anaphylactic reactions, severe skin reaction) to beta-lactam antibiotics (that is, to penicillins or cephalosporins), children's age (up to 3 months).

Carefully:

- with concomitant administration with nephrotoxic drugs;

- Persons with gastrointestinal disorders, especially those suffering from colitis.

Pregnancy and lactation:The use of the drug during pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential risk to the fetus. If it is necessary to use the drug during lactation, it is necessary to solve the problem of terminating difficult feeding.

Dosing and Administration:Intravenously.

Intravenously bolus in dilution with water for injection of 20 ml per 1000 mg of meropenem for at least 5 minutes.

Intravenously infuzionalno for 15-30 minutes in the dilution to 50-200 ml of compatible infusion fluid.

It is recommended to use a freshly prepared solution of meropenem.

The drug diluted with water for injection or 0.9% solution of sodium chloride, maintains a satisfactory efficiency when stored in a refrigerator (at a temperature of up to 4 ° C) for 48 hours.

The drug diluted in the following solvents is 0.9% solution of sodium chloride, 5% a solution of dextrose and 0.225% solution of sodium chloride, 10% dextrose solution, 5% dextrose solution and 0.02% sodium solution bicarbonate, preserves satisfactory storage efficiency at room temperature (below 25 ° C) for the time indicated in the following table:

Solution of the drug

Duration of storage

at 25 ° C

Solutions (1-20 mg / ml) prepared using:

- 0.9% solution of sodium chloride

- 5% solution of dextrose and 0.225% solution of sodium chloride

- 10% dextrose solution

- 5% dextrose solution and 0.02% sodium bicarbonate solution

8 ocloc'k

3 hours

2 hours

The dose and duration of treatment should be determined depending on the type and severity of the infection and the condition of the patient.

The following daily doses are recommended:

- Adults with pneumonia, urinary tract infections, andInfectious-inflammatory diseases of the pelvic organs, skin infections and soft tissues - intravenously, 500 mg every 8 hours.

- With hospital pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, septicemia - intravenously, 1000 mg 3 times a day.

- With meningitis of 2000 mg every 8 hours.

- In chronic renal failure (CRF), the dose is adjusted, depending on the creatinine clearance:

Creatinine clearance (ml / min)	The dose (depending on type infection)	Periodicity introduction of
26-50	The recommended dose	In 12 hours
10-25	Half the recommended dose	In 12 hours
less than 10	Half the recommended dose	After 24 hours

- If there is a violation of the liver, there is no need to adjust the dose.

- Children from 3 months to 12 years of age receive a single dose for intravenous administration - 10-20 mg / kg 3 times a day; Children weighing more than 50 kg are given doses for adults; with meningitis - intravenously 40 mg / kg every 8 hours.

Experience with children with impaired renal function is absent.

Meropenem is excreted in hemodialysis and hemofiltration. It is recommended, so that the drug (depending on the type and severity of the infection) was introduced at the end of the hemodialysis procedure to restore the effective concentration in the blood plasma.

Side effects:From the digestive side system: pain in the epigastric region, nausea, vomiting, diarrhea, constipation, anorexia, jaundice, oral cavity candidiasis, pseudomembranous colitis.

From the nervous system: headache, dizziness, paresthesia, agitation, impaired consciousness, epileptiform seizures, convulsions.

From the urinary system: dysuria, edema, renal dysfunction (hypercreatininaemia, increased urea concentration in plasma), hematuria.

Allergic reactions: skin itching, skin rash, urticaria, multiforme exudative erythema, malignant exudative erythema (Stevens-Johnson syndrome), angioedema, anaphylactic shock.

Laboratory indicators: thrombocytosis, eosinophilia, thrombocytopenia, hemoglobin reduction, hematocrit, leukopenia, shortening of prothrombin and partial thromboplastin time, leukocytosis, hypokalemia, hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase.

Other: positive direct or indirect samples of Coombs, anemia, hypervolemia, dyspnea, vaginal candidiasis.

Local reactions: inflammation, phlebitis, thrombophlebitis, edema and soreness at the injection site.

Causal connection with the use of meropenem is not established: fainting, hallucinations, depression, anxiety, increased excitability, insomnia, cholestatic hepatitis, heart failure, cardiac arrest, tachycardia, bradycardia, myocardial infarction,decrease or increase in blood pressure, thromboembolism of the pulmonary artery, dyspnea.

Overdose:

Symptoms: manifested mainly from the central nervous system (confusion, dizziness, impaired consciousness, seizures like epileptic seizures). In addition, gastrointestinal disorders (eg, nausea) and erosive lesions of the mucous membranes of the gastrointestinal tract, lengthening of the interval QT.

Treatment symptomatic. In patients with renal impairment, hemodialysis effectively removes meropenem and its metabolite.

Interaction:

Meropenem is compatible with the following infusion liquids:

- 0.9% solution of sodium chloride;

- 5% - 10% solution of dextrose (glucose);

- 5% dextrose (glucose) solution with 0.02% sodium bicarbonate solution;

- 0,9% solution of sodium chloride and 5% solution of dextrose (glucose);

- 5% dextrose (glucose) solution with 0.225% solution of sodium chloride;

- 5 % a solution of dextrose (glucose) with 0.15% solution of potassium chloride;

- 2.5% or 10% solution of mannitol.

Meropenem should not be mixed or added to other medications.

Meropenem reduces the plasma concentration of valproic acid, which can lead to a decrease in anticonvulsant effect.

Drugs that block tubular secretion, slow down excretion and increase the concentration of meropenem in the plasma.

Special instructions:

Treatment of patients with liver disease should be conducted under careful monitoring of the activity of "hepatic" transaminases and bilirubin concentration.

In the process of treatment, it is possible to develop resistance pathogens, and therefore prolonged treatment is carried out under the constant control of the spread of resistant strains. In persons with complaints from the gastrointestinal tract (GIT), especially those suffering from colitis, It is necessary to take into account the possibility of developing pseudomembranous colitis (toxin produced Clostridium difficile, is one of the main causes of colitis associated with antibiotics), the first symptom of which can be the development of diarrhea on the background of treatment.

In monotherapy of a known or suspected lower respiratory tract infection of severe course caused by Pseudomonas aeruginosa, it is recommended to regularly determine the sensitivity of the pathogen.

Experiments with the use of the drug in children with neutropenia with primary or secondary immunodeficiency do not.

Effect on the ability to drive transp. cf. and fur:In the period of treatment, there may be headaches, dizziness, paresthesia and seizures, therefore, care should be taken when driving vehicles, other mechanisms, and engaging in potentially dangerous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Powder for the preparation of a solution for intravenous administration of 1000 mg.

Packaging:

For 1000 mg of active substance in a colorless glass vial of 30 ml, sealed with butyl cork of a gray color and closed with an aluminum cap with a tear-off lid of the "flip-off" type.

One bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

In dry, dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000901

Date of registration:18.10.2011

Expiration Date:18.10.2016

Date of cancellation:2017-03-23

Information update date: & nbsp23.03.2017

Illustrated instructions

Instructions

Meropenem-Veksta (Meropenem Vexta)