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

Antibiotic for parenteral use from the group of Karabapenems, has a bactericidal action (suppresses the synthesis of the bacterial cell wall), easily penetrates the bacterial cell wall, is resistant to the action of most beta-lactamases. Virtually does not degrade in the renal tubules dehydropeptidase-1 (no nephrotoxic degradation products are formed), has a high affinity for proteins that bind penicillin.

Bactericidal and bacteriostatic concentrations practically do not differ.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.

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

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.

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 diversus, Citrobacter fireundii, Enterobacter cloacae, Haemophilus influenzae (ampicillin-resistant, penicillinase-sparing strains), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (penicillinase-inducing and penicillin-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 250 mg for 30 minutes, the maximum concentration (C_mOh) - 11 mcg / ml, for a dose of 500 mg - 23 mcg / ml, 1 g - 49 mcg / ml (absolute pharmacokinetic proportional dependence on the administered dose for C_mOh and AUC no). When the dose is increased from 0.25 to 2 g, the clearance decreases from 287 to 205 ml / min. With intravenous bolus administration for 5 min 500 mg C_mOh - 52 mcg / ml, 1 g - 112 mcg / ml. Connection with plasma proteins-2%.

Well penetrates into most tissues and body fluids, incl. in 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 metabolita. The half-life (T_1/2) - 1 h, in children under 2 years - 1.5-2.3 hours. In the dose range of 10-40 mg / kg in adults and 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 meropime in urine exceeding 10 μg / ml is maintained for 5 hours after the administration of 500 mg. In patients with renal failure, clearance is correlated with creatinine clearance (CC). 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 excreted in hemodialysis.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to meropenem:

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

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

- urinary tract infections (including pyelonephritis, pyelitis);

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

- infections of the pelvic organs (including endometritis);

- bacterial meningitis;

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

Contraindications:

Hypersensitivity to meropenem (including other beta-lactam antibiotics), components of the drug; children's age (up to 3 months).

Carefully:

Pregnancy, lactation.

Pregnancy and lactation:

In pregnancy and lactation, it is necessary to evaluate the potential benefit to the mother and the possible risk of using meropenem for the fetus and the baby.

Dosing and Administration:

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

Doses and duration of therapy 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 and children over 12 years of age and weighing more than 50 kg:

500 mg intravenously every 8 hours for pneumonia, urinary tract infections, gynecological infections and pelvic inflammatory diseases, skin and soft tissue infections.

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

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

In chronic renal failure, the dose is adjusted depending on the CK: with KK 26-50 ml / min - 0.5-1 g 2 times a day, 10-25 ml / min - 250-500 mg 2 times a day, less than 10 ml / min - 500 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.

Children

For children aged 3 months to 12 years, or with a body weight of less than 50 kg, 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.

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, the drug is dissolved in sterile water for injection (10 ml per 500 mg of meropenem). This provides a solution concentration of 50 mg / ml.

For intravenous infusions, the drug is dissolved in sterile water for injection or in a compatible infusion fluid (50 to 200 ml).

Meropenem is compatible with the following infusion liquids:

- sodium chloride 0.9% solution;

- dextrose 5 % or 10% solution;

- 5% dextrose solution with 0.02% sodium bicarbonate;

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

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

- 5% dextrose solution with 0.1 5% potassium chloride solution;

- 2.5% or 10% mannitol solution.

Meropenem should not be mixed with solutions containing other drugs.

Side effects:

From the digestive system: pain in the epigastric region, nausea, vomiting, diarrhea, constipation, anorexia, jaundice, candidiasis of the oral mucosa, pseudomembranous colitis.

From 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: itching of the skin, skin rash, urticaria, multiforme exudative erythema, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, angioedema edema, anaphylactic shock.

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

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

Local reactions: inflammation, phlebitis, thrombophlebitis, tenderness, edema at the site of administration.

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

Overdose:

Accidental overdose is possible during treatment, especially in patients with impaired renal function.

Symptoms: increased severity of side effects.

Treatment: symptomatic therapy. Normally, there is rapid elimination of the drug by the kidneys. In patients with impaired renal function, hemodialysis is effective.

Interaction:

Compatible with 0.9% solution of sodium chloride, 5 % or 10% dextrose solution, with 0.02 % solution of sodium bicarbonate, 5 % solution of dextrose with 0.225% sodium chloride solution, 5% dextrose solution with 0.15% potassium chloride solution, 2.5 % solution of mannitol.

It shows antagonism when interacting with beta-lactam antibiotics.

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

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

Special instructions:

Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may exhibit hypersensitivity to meropenem.

The use of meropenem in infections caused by methicillin-resistant staphylococcus is not recommended.

Treatment of patients with liver disease should be conducted under the control 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 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 monotherapy of an established or suspected lower respiratory infection of severe course caused by Pseudomonas aeruginosa, a regular determination of the sensitivity of the pathogen is recommended.

Experience with the use of meropenem in children with neutropenia, with primary or secondary immunodeficiency is absent.

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

During the treatment period, care should be taken when driving a car and engaging in other potentially hazardous activities,requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for intravenous administration.

Packaging:

For 500 mg of active substance in a bottle of clear, colorless glass type I with a butyl rubber rubber stopper and a combined aluminum-plastic cap.

1 bottle together with the instruction for use is placed in a cardboard box. 10 packets are placed in a cardboard box.

Storage conditions:

In a dry, dark place at a temperature of no higher than 20 ° 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:LP-001019

Date of registration:18.10.2011

Expiration Date:18.10.2016

Information update date: & nbsp01.05.2018

Illustrated instructions

Instructions

Meronoxol® (Meronoksol®)