Mepenem - instructions for use, doses, side effects, contraindications

Meropenem is an antibiotic from the carbapenem group for parenteral use, it has bactericidal action. It 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 death of bacteria.Resistant to the action of dehydropeptidase-1, it easily penetrates the bacterial cell wall, is resistant to the action of most beta-lactamases. Among the known beta-lactam antibiotics has the highest activity against most aerobic and anaerobic gram-positive and gram-negative microorganisms.

Active in vitro and in vivo in a relationship:

Gram-positive aerobes: Enterococcus faecalis (excluding vancomycin-resistant strains), Staphylococcus aureus (methicillin-sensitive); Staphylococcus spp. (methicillin-sensitive), incl. Staphylococcus epidermidis; Streptococcus agalactiae; Streptococcus pneumoniae; Streptococcus pyogenes, Group Streptococcus milleri (Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius).

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, Serratia marcescens.

Gram-positive anaerobes: Clostridium perfringens, Peptoniphilus asaccharolyticus, Peptostreptococcus spp., including Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptococcus magnus.

Gram-negative anaerobes: Bacteroides caccae, Bacteroides fragilis, Prevotella bivia, Prevotella disiens.

Microorganisms for which the problem of acquired resistance is relevant:

GrampolozhAerobics: Enterococcus faecium.

Gram-negative aerobes: Acinetobacter spp., Burkholderia cepacia, Pseudomonas aeruginosa.

Microorganisms possessing natural resistance: Stenotrophomonas maltophilia, Legionella spp., Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetti, Mycoplasma pneumoniae.

Pharmacokinetics:

With a single intravenous (IV) administration within 30 minutes, the maximum concentration (Cmax) of meropenem in plasma is 23 μg / ml for a dose of 500 mg and 49 μg / ml for a dose of 1 g.Stam in plasma after 5 minutes of bolus injection is 52 μg / ml for a dose of 500 mg and 112 μg / ml for a dose of 1 g.

Well penetrates into most tissues and body fluids, incl. in the cerebrospinal fluid (CSF) 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.

Binding to plasma proteins is approximately 2%. Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite. The half-life (T_1/2) - 1 hour, in children under 2 years - 1.5-2.3 hours. In the dose range of 10-40 mg / kg in children, a linear dependence of pharmacokinetic parameters is observed. 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, clearance is correlated with clearance creatinine (QA). In elderly patients, a decrease in meropenem clearance correlates with a decrease in QC associated with age. T_1/2- 1.5 h.It is in hemodialysis.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to meropenem (monotherapy or in combination with other antimicrobial drugs):

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

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

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

- skin and soft tissue infections (including erysipelas, impetigo, secondarily infected dermatoses);

- bacterial meningitis;

- septicemia;

Infectious-inflammatory diseases of the pelvic organs (including endometritis).

Empirical treatment (in the form of monotherapy or combination with antiviral or antifungal drugs) with a suspected bacterial infection in adult patients with febrile episodes against neutropenia.

Contraindications:

Hypersensitivity to meropenem, other components of the drug and other carbapenems, severe hypersensitivity (anaphylactic reactions, severe skin reactions) to other beta-lactam antibiotics (ie to penicillins or cephalosporins); children's age (up to 3 months).

Carefully:

When used simultaneously with nephrotoxic drugs, patients with complaints from the gastrointestinal tract, especially with colitis.

Pregnancy and lactation:

The safety of the use of meropenem in women during pregnancy has not been studied. The drug should not be used during pregnancy, except when the potential benefit of its use for the mother exceeds the possible risk to the fetus. In each case, the drug should be administered under strict medical supervision. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration:

Intravenous bolus for at least 5 minutes, or as an intravenous infusion during 15-30 minutes.

Dosage 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:

Adults

0.5 g intravenously every 8 hours for pneumonia, infections of the urinary system, infectious and inflammatory diseases of the pelvic organs, infections of the skin and soft tissues.

1 g intravenously every 8 hours with hospital pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, and septicemia.

With bacterial meningitis, the recommended dose is 2 g every 8 hours.

In chronic renal insufficiency, the dose is adjusted depending on the creatinine clearance (CC): for KK 26-50 ml / min - 0.5-1-2 g 2 times a day, 10-25 ml / min - 250-500- 1000 mg twice a day, less than 10 ml / min - 250-500-1000 mg once a day.

Meropenem is excreted in hemodialysis. If long-term treatment is required, it is recommended that the dose unit (determined depending on the type and severity of the infection) be introduced at the end of the hemodialysis procedure to restore the effective plasma concentration. Currently, there is no evidence of experience with the use of meropenem in patients on peritoneal dialysis.

In patients with hepatic insufficiency, dose adjustment is not required.

In elderly patients with QC more than 50 ml / min dose adjustment is not required.

Children

For children aged 3 months to 12 years, the recommended dose for intravenous administration is 10-20 mg / kg body weight every 8 hours, depending on the type and severity of the infection, the sensitivity of the pathogen and the patient's condition.Children with a body weight of more than 50 kg should use doses for adults.

With meningitis, the recommended dose is 40 mg / kg every 8 hours.

There is no experience of using the drug in children with impaired liver and kidney function.

Preparation of solutions

For intravenous bolus injections meropenem should be diluted with sterile water for injection (10 ml per 500 mg of the drug). This provides a solution concentration of 50 mg / ml.

For intravenous infusion meropenem diluted with a compatible infusion fluid (50 to 200 ml).

Meropenem is compatible with the following infusion liquids:

- 0.9% solution of sodium chloride;

- 5% or 10% dextrose solution;

- 5% dextrose solution with 0.02% sodium bicarbonate;

- 0.9% solution of sodium chloride and 5% solution of dextrose;

- 5% a solution of dextrose with 0.225% sodium chloride solution;

- 5% dextrose solution with 0.15% potassium chloride solution;

- 2.5% and 10% mannitol solution.

Meropenem should not be mixed with solutions containing other drugs. For intravenous injections and infusions, a freshly prepared solution of meropenem is recommended.

Side effects:

From the digestive system: nausea, vomiting, diarrhea, increased activity of "liver" transaminases, alkaline phosphatase, lactate dehydrogenase, hyperbilirubinemia, pseudomembranous colitis.

On the part of the hematopoiesis system: thrombocytosis, eosinophilia, Thrombocytopenia, leukopenia, neutropenia, agranulocytosis, hemolytic anemia.

From the nervous system: headache, paresthesia, convulsions.

Allergic reactions: itching of the skin, skin rash, urticaria, multiforme exudative erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, anaphylactic shock.

From the urinary system: hyperkreatininemia, increased urea concentration in plasma.

Local reactions: inflammation, thrombophlebitis, tenderness at the injection site.

Other: positive direct or indirect samples of Coombs, reduction of partial thromboplastin time, vaginal candidiasis, candidiasis of the oral mucosa.

Causal connection with the use of meropenem is not established: constipation, cholestatic hepatitis, heart failure, cardiac arrest, tachycardia, bradycardia, myocardial infarction, decreased or increased blood pressure, pulmonary embolism, syncope, hallucinations, depression, anxiety, increased excitability, insomnia, dyspnea.

Overdose:

Accidental overdose is possible during treatment, especially in patients with impaired renal function, it is possible to increase dose-dependent side effects.

Treatment in case of an overdose should be symptomatic. When hemodialysis occurs, rapid elimination of the drug.

Interaction:

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

The possible effect of meropenem on the degree of association of other drugs with plasma proteins or metabolism has not been studied. The association of meropenem with plasma proteins is low (about 2%), so interaction with other drugs based on the mechanism of displacement from plasma protein binding is not expected.

Meropenem can reduce the concentration of valproic acid in the blood serum. In some patients, concentrations below therapeutic may be achieved.The combined use of carbapenems and valproic acid preparations led to a decrease in the concentration of valproic acid in blood plasma by 60-100% after 2 days of therapy. Due to the rapid and significant decrease in the concentration of valproic acid, the combined use of meropenem and valproic acid preparations is not recommended.

There are no specific data on possible drug interactions (with the exception of probenecid).

The use of meropenem during the administration of other drugs was not accompanied by the development of unfavorable pharmacological interactions.

Special instructions:

Experience with the use of meropenem in pediatric practice in patients with neutropenia or with primary or secondary immunodeficiency is not present.

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

When using meropenem, the development of pseudomembranous colitis (toxin produced Clostridium difficile, is one of the main causes of colitis associated with antibiotics), which can vary in severity from mild to life-threatening forms.It is important to remember the possibility of developing pseudomembranous colitis when diarrhea occurs on the background of treatment.

Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may exhibit hypersensitivity to meropenem. Before starting treatment, you should carefully question the patient for any history of allergic reactions. When occurrence of an allergic reaction to meropenem, it is necessary to stop the introduction of the drug and take appropriate measures.

Treatment of patients with liver diseases should be carried out under careful monitoring of the activity of "liver" transaminases and bilirubin concentrations.

In the process of treatment, the development of resistance of pathogens is possible, in connection with which long-term treatment is carried out under the constant control of the spread of resistant strains. The use of meropenem in infections caused by methicillin-resistant strains is not recommended Staphylococcus spp.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Powder for solution for intravenous injection, 1.0 g.

Packaging:

The amount of the preparation, containing 1.0 g of meropenem, into a 20 ml bottle of clear glass, sealed with a stopper of chlorobutyl rubber, crimped with an aluminum ring and a safety plastic cap on which the logo is marked "Elfa".

1 bottle with instructions for use in a cardboard box.

Storage conditions:Keep in dry the dark place at a temperature of no higher than 25 ° C. Store in inaccessible to children.

Meropenem diluted as described above retains satisfactory performance when stored at room temperature (below 25 ° C) or when stored in refrigerator (up to 4 ° C) for the time indicated in the following table:

Solvent	Duration of storage (h)
Solvent	At 15-25FROM	When 4 ° С
Vials, diluted with water for injection, intended for bolus injection	8	48
Solutions (1-20 mg / ml), prepared with:
- 0,9% sodium chloride;	8	48
- 5% dextrose;	3	14
- 5% dextrose and 0.225% sodium chloride;	3	14
- 5% dextrose and 0,9% sodium chloride;	3	14
- 5% dextrose and 0.15% potassium chloride;	3	14
- 2,5% or 10% Mannitol for intravenous infusions;	3	14
- 10% dextrose;	2	8
5% dextrose and 0.02% sodium bicarbonate for IV infusion.	2	8

The solution of Meropenem should not be frozen.

Shelf life:

3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002354

Date of registration:28.01.2014 / 26.07.2016

Expiration Date:28.01.2019

The owner of the registration certificate:ELFA NPC, CJSC ELFA NPC, CJSC Russia

Manufacturer: & nbsp

ELFA LABORATORIES India

Representation: & nbspZAO NPC ELFA ZAO NPC ELFA Russia

Information update date: & nbsp04.09.2016

Illustrated instructions

Instructions

Mepenem (Mepenem)