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

Has a bactericidal effect by suppressing the synthesis of the bacterial cell wall. The bactericidal effect of meropenem against a wide range of aerobic and anaerobic bacteria is explained by the high capacity of meropenem to penetrate the bacterial cell wall, a high level of stability to most beta-lactamases and a significant affinity for proteins that bind penicillin.

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 (as a result of structural similarity), suppresses transpeptidase,promotes the release of autolytic enzymes of the cell wall, which eventually causes its damage and death of bacteria.

Bactericidal and bacteriostatic concentrations practically do not differ.

Activity spectrum

Gram-positive aerobes:

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

Gram-negative aerobes:

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

Anaerobic bacteria:

Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus spp.

With respect to the following microorganisms meropenem effective in vitro, However, clinically, its effectiveness in diseases caused by these pathogens is not proven:

Gram-positive aerobes:

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

Gram-negative aerobes:

Acinetobacter spp., Aeromonas hydrophila, Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Haemophilus influenzae (ampicillin-resistant, penicillinase-sparing strains), Hafiiia alvei, Klebsiella oxytoca, Moraxella catarrhalis (penicillinase-inducing and penicillin-producing), Morganella morganii, Pasteurella multocida, Proteus vulgaris, Salmonella spp., Serratia j 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:

With intravenous administration 250 mg for 30 minutes the maximum concentration (Cmah) is 11 μg / ml, for a dose of 500 mg - 23 μg / ml, for a dose of 1 g - 49 μg / ml.

With an increase in the dose from 250 mg to 2 g, the clearance of meropenem decreases from 287 to 205 ml / min.

With intravenous bolus administration for 5 min, 500 mg meropenem Cmah is 52 μg / ml, 1 g -112 μg / ml. Connection with blood plasma proteins - 2%.

Well penetrates most tissues and body fluids, incl. at cerebrospinal fluid in patients with bacterial meningitis, reaching concentrations higher than 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.

It is subject to a slight metabolism in the liver with the formation of a single microbiologically inactive metabolite.

The half-life is 1 hour, in children under 2 years - 1.5 - 2.3 hours.

The pharmacokinetics of meropenem in children and adults is similar; in the diapaseon the dose of 10-40 mg / kg observed 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 the creatinine clearance. Such patients need dose adjustment.

In elderly patients decline the clearance of meropenem correlates with the age-related decrease in creatinine clearance. The half-life is 1.5 hours. Meropenem is excreted by hemodialysis.

Indications:

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

- infections of the lower respiratory tract (including pneumonia, including hospital ones);

- infection of the abdominal cavity (complicated appendicitis, peritonitis, pelvioperitonitis);

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

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

- infections of the pelvic organs (including endometritis);

- bacterial meningitis;

- septicemia;

- empirical treatment (in the form of monotherapy or in combination with antiviral or antifungal drugs) with suspected infection in adult patients with febrile neutropenia.

Contraindications:

Hypersensitivity to meropenem or other beta-lactam antibiotics in the anamnesis, children's age to 3 months.

Carefully:

Simultaneous administration with potentially nephrotoxic drugs.

Persons with complaints from the gastrointestinal tract (including with colitis).

Pregnancy and lactation:

Meropenem should not be used during pregnancy, except when the potential benefit from its use justifies the possible risk to the fetus.

Meropenem should not be used during lactation, except when the potential benefit from its use justifies the possible risk to the child.If you need to use the drug during lactation, you should consider stopping breastfeeding.

Dosing and Administration:

Intravenously bolus for at least 5 minutes or intravenously infusion for 15-30 minutes, using appropriate infusion solutions for dilution.

The dose and duration of therapy should be set depending on the type and the severity of the infection, as well as the condition of the patient.

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

1 g 3 times a day with hospital pneumonia, peritonitis, septicemia, suspected bacterial infection in patients with febrile neutropenia.

In the treatment of meningitis, the recommended dose is 2 g every 8 hours.

When chronic renal failure the dose is corrected depending on the creatinine clearance:

Creatinine clearance (ml / min)	Dose	Frequency of administration
26-50	500 mg - 1.0-2.0 g	every 12 hours
10-25	250-500 mg-1.0 g	every 12 hours
<10	250-500 mg-1.0 g	every 24 hours

Meropenem is excreted in hemodialysis.If long-term treatment with meropenem is required, it is recommended to administer the dose of the drug (according to the type and severity of the infection) at the end of the hemodialysis procedure in order to restore the effective concentration in the blood plasma.

In patients with hepatic insufficiency there is no need for dose adjustment.

In elderly patients with normal renal function or creatinine clearance greater than 50 mL / min dose adjustment is not required.

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 the infection, the sensitivity of the pathogen and the patient's condition.

Children up to 12 years old with a body weight of more than 50 kg doses for adults should be used.

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

Experience with children with impaired renal function is absent.

Preparation of solutions

Meropenem for intravenous bolus injections should be diluted with sterile water for injection (20 ml per 1 g of meropenem), with a solution concentration of about 50 mg / ml. The resulting solution is a clear liquid (colorless or light yellow).

Meropenem for intravenous infusions can be diluted with a compatible infusion solution (from 50 to 200 ml).

Meropenem is compatible with the following infusion solutions:

- 0,9% solution of sodium chloride;

- 5% or 10% dextrose solution.

When diluting meropenem should follow the measures of aseptic and antiseptic. Dissolve the diluted solution before use. All vials are for single use only.

Meropenem should not be mixed in the same bottle with other drugs.

Side effects:

From the digestive system: epigastric pain, nausea, vomiting, diarrhea, constipation, anorexia, jaundice, cholestatic hepatitis, hyperbilirubinemia, increased activity of "liver" transaminases, alkaline phosphatase, lactate dehydrogenase; rarely - candidiasis of the oral mucosa, pseudomembranous colitis.

From the side of the cardiovascular system: development or exacerbation of heart failure, cardiac arrest, tachy- or bradycardia, a decrease or increase in blood pressure, fainting, myocardial infarction, thromboembolism of the branches of the pulmonary artery.

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

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

From the nervous system: headache, dizziness, paresthesia, insomnia, drowsiness, increased excitability, agitation, anxiety, depression, impaired consciousness, hallucinations, epileptiform seizures, convulsions.

Laboratory indicators: eosinophilia, neutropenia, leukopenia, rarely agranulocytosis, hypokalemia, leukocytosis, reversible thrombocytopenia, reduction of partial thromboplastin time, anemia.

Local reactions: inflammation, phlebitis, thrombophlebitis, tenderness at the injection site. Other: positive direct or indirect samples of Coombs, hypervolemia, dyspnea, vaginal candidiasis.

Overdose:

Possible overdose during treatment, especially in patients with impaired renal function.

Treatment: conduct symptomatic therapy. Normally, there is rapid elimination of the drug through the kidneys. In patients with impaired renal function, hemodialysis effectively removes meropenem and its metabolite.

Interaction:

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

Can reduce the concentration of valproic acid in the blood plasma.

Special instructions:

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

In the course of treatment, the development of resistance of pathogens is possible, and therefore prolonged treatment is carried out under the constant control of the distribution of resistant strains.

In persons with diseases of the gastrointestinal tract, especially with 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.

When using meropenem as monotherapy in critically ill patients with an identified lower respiratory tract infection caused by Pseudomonas aeruginosa, or if it is suspected, it is recommended that a test be carried out regularly on the sensitivity of the pathogen to meropenem.

Experience in the use of the drug in children with neutropenia, with primary or secondary immunodeficiency is not.

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

During the treatment period, until the individual response to the meropenem, patients should refrain from driving motor vehicles and other activities that require high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for intravenous injection, 1.0 g.

Packaging:

By 1.0 g of active substance in bottles with a capacity of 20 ml of transparent colorless glass, sealed with rubber stoppers and crimped with aluminum caps with a plastic seal.

1 or 10 bottles together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-002913/10

Date of registration:07.04.2010 / 13.04.2015

Expiration Date:Unlimited

The owner of the registration certificate:FARMGID CJSCFARMGID CJSC Russia

Manufacturer: & nbsp

GALPHA LABORATORIES, Limited India

Information update date: & nbsp01.05.2018

Illustrated instructions

Instructions

Meropenem (Meropenem)