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Active material: Meropenem
When ATH: J01DH02
CCF: Antibiotic group of carbapenems
ICD-10 codes (testimony): A39, A40, A41, G00, J15, K65.0, L01, L02, L03, L08.0, N10, N11, N15.1, N30, N34, N70, N71, N72, N73.0, Z29.2
When CSF: 06.04
Manufacturer: ASTRAZENECA UK Ltd. (Great Britain)

Pharmaceutical form, composition and packaging

Valium for drug of a solution for / in powder from white to white with a yellowish tint.

Excipients: anhydrous sodium carbonate,.

Vials 10 ml (10) – cardboard boxes.
Vials 20 ml (10) – cardboard boxes.

Valium for drug of a solution for / in powder from white to white with a yellowish tint.

Excipients: anhydrous sodium carbonate,.

Vials 30 ml (10) – cardboard boxes.

Pharmacological action

Group of carbapenem antibiotic for parenteral administration, resistant to dehydropeptidase-1 (BPD-1) man, It requires no additional administration of an inhibitor of BPH-1.

Meropenem has a bactericidal effect by acting on the synthesis of the bacterial cell wall. Powerful bactericidal activity against a broad spectrum of meropenem aerobic and anaerobic bacteria due to the high ability to penetrate the cell wall of bacteria, high level of stability to most β-lactamases and significant affinity to proteins, svyazıvayuşçïm penicillin (BSP). The minimum bactericidal concentrations (MBK) usually the same, as the minimum inhibitory concentration (MIK). To 76% Tested bacteria ratio of MBC / MIC was 2 or less.

Meropenem is stable in susceptibility tests determination. Tests in vitro show, that meropenem acts synergistically with various antibiotics. Has been shown in vitro and in vivo, that meropenem has postantibioticski effect.

The only recommended criteria of sensitivity to meropenem based on pharmacokinetics and correlation of clinical and microbiological data – zone diameter and MIC, determined for the relevant pathogens.

The spectrum of antibacterial activity of meropenem, determined in vitro, It includes virtually all clinically important gram-positive and gram-negative aerobic and anaerobic microorganisms.

Preparation active against aerobic Gram-positive bacteria: Bacillus spp., Corynebacterium diphtheriae, Enterococcus liquifaciens, Enterococcus avium, Listeria monocytogenes, Lactobacillus spp., Nocardia asteroids, Staphylococcus aureus (strains, producing and not producing penicillinase), coagulase-negative staphylococci, incl. Staphylococcus saprophyticus, Staphylococcus, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus warneri, Staphylococcus man, Staphylococcus simulating, Staphylococcus intermedius, Staphylococcus aureus, Staphylococcus lugdenensis, Streptococcus pneumoniae (sensitive and penicillin-resistant), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus, Streptococcus, Streptococcus milleri, Streptococcus, Streptococcus viridans, Streptococcus salivarius, Streptococcus disease, Streptococcus Group G, Group F, Rhodococcus equi; Aerobic Gram-negative bacteria: Achromobacter xylosoxidans, Acinetobacter anitratus, Acinetobacter lwoffii, Acinetobacter baumannii, Aeromonas hydrophila, Aeromonas sorbria, Aeromonas caviae, Alcaligenes faecalis, Bordetella bronchiseptica, Brucella melitensis, Campylobacter coli, Campylobacter jejuni, Citrobacter freundii, Citrobacter different, Citrobacter koseri, Citrobacter amalonaticus, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter sakazakii, Escherichia coli, Escherichia hermannii, Gardnerella vaginalis, Haemophilus influenzae (including strains, продуцирующие b-лактамазы, and ampicillin-resistant strains), Haemophilus parainfluenzae, Haemophilus ducreyi, Helicobacter pylori, Neisseria meningitidis, Neisseria gonorrhoeae (including strains, продуцирующие b-лактамазы, and resistant to penicillin and spectinomycin), Hafnia avenue, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella catarrhalis, Morganella morgannii, Proteus is wonderful, Proteus vulgaris, Proteus penneri, Rettgeri Providence, Providence stuartii, Alcalifaciens Providence, Pasteurella multocida, Plesiomonas shigelloides, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas alcaligenes, Pseudomonas cepacia, Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas pseudomallei, Pseudomonas acidovorans, Salmonella spp., including Salmonella enteritidis, Salmonella typhi, Serratia wilting, Serratia dissolving, Serratia rubidaea, Shigella sonnei, Shigella flexneri, Shigella boydii, Shigella dysentery, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio injurious, Yersinia enterocolitica; Anaerobic bacteria: Actinomyces odontolyticus, Actinomyces meyeri, Bacteroides-Prevotella-Porphyromonas spp., Bacteroides fragilis, Bacteroides vulgatus, Bacteroides variable, Bacteroides pneumosintes, Bacteroides coagulans, Bacteroides uniform, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides eggerthii, Bacteroides capsillosis, Prevotella buccalis, Prevotella body, Bacteroides gracilis, Prevotella melaninogenica, Prevotella intermedia, Prevotella crossroads, Prevotella splanchnicus, Oral Prevotella, Prevotella disiens, Prevotella rumenicola, Prevotella ureolyticus, Prevotella of the mouth, Prevotella mouth, Prevotella denticola, Prevotella levii, Porphyromonas asaccharolyticus, Bifidobacterium spp., Bilophilia wadsworthia, Clostridium perfringens, Clostridium bifermentans, Clostridium ramosum, Clostridium sporogenes, Clostridium corpse, Clostridium sordellii, Clostridium butyricum, Clostridium clostridiiformis, Bacteria harmless, Clostridium subterminale, Clostridium third, Eubacterium landed, Eubacterium aerofaciens, The deadly bacteria, Fusobacterium necrophorum, Fusobacterium nucleatum, Fusobacterium varied, Mobiluncus curtisii, Mobiluncus woman, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus saccharolyticus, Peptococcus saccharolyticus, Peptococcus asaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus prevotii, Propionibacterium acnes, Propionibacterium avidius, Propionibacterium granulosum.

C drug resistant Stenotrophomonas maltophilia, Enterococcus faecium and methicillin-resistant staphylococci.

Meronem demonstrated efficacy as a monotherapy or in combination with other antimicrobial agents in the treatment of polymicrobial infections.

Pharmacokinetics

Distribution

B / in administering for 30 min single dose to healthy volunteers results in a C_max, of about 11 ug / ml for a dose 250 mg, 23 ug / ml for a dose 500 mg 49 ug / ml for a dose 1 g. However, there is no absolute pharmacokinetic proportional to the administered dose or for C_max, neither for AUC. Furthermore, observed a decrease in plasma clearance from 287 to 205 ml / min for doses of 250 mg 2 g.

B / bolus injection for 5 min single dose to healthy volunteers Meronema leads to the achievement of C_max, of about 52 ug / ml for a dose 500 mg 112 ug / ml – for dose 1 g.

C_max plasma with / in a 1 g of drug over 2 m, 3 Mines and 5 min made 110, 91 and 94 ug / ml, respectively.

Plasma protein binding – about 2%. Meropenem penetrates well in most tissues and body fluids, incl. in the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations, greater than required to inhibit most bacteria.

Through 6 h after i / v administration 500 mg meropenem plasma level falls below the 1 ug / ml or less. When multiple doses administered at intervals of 8 hours in patients with normal renal function, accumulation of meropenem does not occur.

Metabolism and excretion

Edinstvennыy meropenem microbiological inactive metabolite.

About 70% of the administered dose is excreted in the urine unchanged within 12 no, after which further urinary excretion of small. The concentration of meropenem in the urine, exceeding 10 mcg / ml is maintained for 5 hr postdose 500 mg. When the mode of administration 500 mg every 8 or h 1 g every 6 h was observed accumulation of meropenem in plasma and urine of volunteers with normal liver function. In patients with normal renal function T_1/2 is approximately 1 no.

Pharmacokinetics in special clinical situations

Meronema pharmacokinetic parameters in children are the same, as in adults. T_1/2 meropenem in children under 2 years – about 1.5-2.3 no, Linear pharmacokinetics observed in the dose range 10-40 mg / kg.

Pharmacokinetic studies of the drug in patients with renal insufficiency have shown, that the clearance of meropenem correlates with creatinine clearance. These patients require a dose adjustment.

Pharmacokinetic studies of the drug in elderly patients showed a decrease in clearance of meropenem, which correlated with a decrease in creatinine clearance, age-related.

Pharmacokinetic studies of the drug in patients with liver disease have shown, that liver disease does not affect the pharmacokinetics of meropenem.

Testimony

Treatment of the following infections in children and adults, caused by one or more sensitive to the drug agents:

- Pneumonia (incl. nosocomial);

- Urinary tract infection;

- Infections of the abdominal cavity;

- Gynecological infections (such as endometriosis and pelvic inflammatory disease);

- Infections of the skin and soft tissues;

- Meningitis;

- Septicemia;

- Empirical therapy for suspected bacterial infection in adult patients with febrile neutropenia episodes in the background, as monotherapy or in combination with antiviral or antifungal drugs.

Dosage regimen

Adults dosing regimen and treatment duration set depending on the type and severity of the infection and condition of the patient. We recommend the following daily doses.

At treatment of pneumonia, infections of the urinary system, gynecological infections (endometritis and inflammatory diseases of the pelvic organs), infections of the skin and soft tissue – 500 mg / in every 8 no.

At the treatment of nosocomial pneumonia, peritonitis, suspected bacterial infection in patients with neutropenia, and septicemia – 1 g / in every 8 no.

At treatment of meningitis – 2 g / in every 8 no.

In patients with impaired renal function at CC 50 ml / min or less the dose must be reduced as follows:.

Meropenem appear in hemodialysis, in this connection, if you want to continue treatment, recommended, that the unit dose (It is determined depending on the type and severity of the infection) It was introduced at the end of hemodialysis, to restore effective plasma concentration.

Experience with patients Meronema, undergoing peritoneal dialysis, missing.

In patients with hepatic insufficiency there is no need to adjust the dose.

In elderly patients with normal renal function or KK more 50 ml / min is not required to adjust the dose.

To children aged 3 Months before 12 years The recommended dose for i / v administration is 10-20 mg / kg every 8 h depending on the type and severity of the infection, pathogen sensitivity and condition of the patient. In Children weighing more than 50 kg should use the same dose as adults.

At meninges The recommended dose is 40 mg / kg every 8 no.

Terms of preparation and administration of the solution

Meronem be administered in the form of I / bolus injection for at least 5 min or as / in infusion for 15-30 m.

For in / bolus Meronem should be diluted with sterile water for injection (5 ml 250 mg of meropenem), providing a solution concentration 50 mg / ml.

For in / infusion Meronem should be diluted with sterile water for injection or infusion fluid and consistent then another breed (to 50-200 ml) compatible infusion fluid.

Meronem is compatible with the following infusion fluids: 0.9% sodium chloride solution for in / infusion; 5% or 10% glucose solution for i / v infusion; 5% glucose solution for I / infusions 0.02% solution of sodium bicarbonate; 0.9% solution of sodium chloride 5% glucose solution for i / v infusion; 5% glucose solution 0.225% sodium chloride solution for in / infusion; 5% glucose solution 0.15% Potassium chloride solution for in / infusion; with mannitol solution 2.5% or 10% for / in infusion.

Meronem should not be mixed with solutions, containing other drugs.

Before using the diluted solution should be shaken. All single-use vial. When breeding Meronema should apply the standard rules of aseptic.

Side effect

Severe side effects are rare. It informs about the following side effects:

Allergic reactions: rarely – angioedema, anaphylactic reactions.

Dermatological reactions: itch, rash, hives; rarely – multiforme (exudative) эritema, Stevens-Johnson syndrome and toksičeskij épidermalʹnyj necrolysis.

From the digestive system: stomach ache, nausea, vomiting, diarrhea; in some cases – reversible increase in blood levels of bilirubin, transaminases, ALP and LDH alone or in combination; in some cases – psevdomembranoznыy colitis.

From the hematopoietic system: reversible thrombocytosis, eozinofilija, thrombocytopenia, leukopenia and neutropenia (including very rare cases of agranulocytosis). In some patients the possibility of a positive direct or indirect Coombs test; also have reported cases of reducing partial thromboplastin time.

From the central and peripheral nervous system: headache, paresthesia; There are reports of seizures, however, a causal relationship with the reception Meronema not installed.

Local reactions: inflammation, tromboflebit, pain at the injection site.

Effects, due to biological activity: oral candidiasis, vaginal candidiasis.

Contraindications

- Hypersensitivity to the drug.

FROM caution It should be prescribed concurrently with potentially nephrotoxic drugs, and patients with symptoms of dyspepsia, especially associated with colitis.

Pregnancy and lactation

Safety of Meronema during pregnancy has not been studied.

Experimental studies in animals have not shown any adverse effects on the developing fetus. The only adverse events, identified in studies in animals on the effect of the drug on the reproductive system, It has increased the frequency of abortions in monkeys at a dose of, in 13 times the recommended human.

Meronem should not be used during pregnancy, unless the potential benefit of its use justifies the potential risk to the fetus. In each case, the drug should be used under the direct supervision of a physician.

Meropenem defined in breast milk of animals at very low concentrations. Meronem should not be used during lactation (breast-feeding), unless the potential benefit of its use justifies the potential risk to the child. If necessary, use during lactation should consider the issue of termination of breastfeeding.

Cautions

As with other antibiotics, using meropenem as monotherapy in critically ill patients with known or suspected infection of the lower respiratory tract, caused by Pseudomonas aeruginosa, It recommends regular definition susceptibility.

Pseudomembranous colitis seen with virtually all antibiotics and may vary in intensity from mild to life-threatening forms. Therefore, antibiotics should be prescribed with caution for people with gastrointestinal complaints, especially in patients with colitis. It is important to bear in mind the diagnosis “psevdomembranoznыy colitis” in the case of diarrhea in patients receiving antibiotic. Although studies have shown, toxin seems to be built, produced by Clostridium difficile is a major cause of colitis, related antibiotics, However, you must bear in mind other reasons.

There are clinical and laboratory signs of hypersensitivity partial cross between carbapenems and other beta-lactam antibiotics, penicillins and cephalosporins. Despite, that allergic reactions with beta-lactam antibiotics is not uncommon, of hypersensitivity reactions during administration Meronema reported rarely. Before therapy meropenem should be carefully interviewed patients, paying special attention to hypersensitivity reactions to beta-lactam antibiotics in history. Meronem should be used with caution in patients with a history of instructions for such phenomena. If an allergic reaction to meropenem, it is necessary to stop the introduction of the drug and take appropriate action.

Application Meronema in patients with liver disease should be carefully monitored levels of transaminases and bilirubin.

As is the case with other antibiotics, possible dominant growth of microorganisms insensitive, and therefore need constant monitoring of each patient.

Application infections, caused by methicillin-resistant staphylococcus, not recommended.

Use in Pediatrics

Efficacy and tolerability in Meronema children aged 3 Months not installed, so the drug is not recommended for use in children younger than 3 Months.

Experience with the drug in pediatric patients with neutropenia or primary or secondary immunodeficiency no.

Experience of using Meronema in children with impaired liver and kidney function no.

Efficacy and tolerability in Meronema children aged 3 Months not installed, so the drug is not recommended for use in children younger than 3 Months.

Effects on ability to drive vehicles and management mechanisms

Meronem has no effect on ability to drive and other equipment.

Overdose

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

Treatment: symptomatic therapy. Normally, there is a rapid elimination of the drug by the kidneys. In patients with renal impairment, hemodialysis effectively remove meropenem and its metabolite.

Drug Interactions

Probenecid competes with meropenem for active tubular secretion and, thus, inhibits the renal excretion of meropenem, causing an increase in its half-life and plasma concentration. Unnecessarily. efficacy and duration of action Meronema without probenecid are adequate, co-administration of probenecid with Meronemom not recommended.

Possible impact Meronema metabolism and protein binding of other drugs has not been studied. But, given the low binding to plasma proteins meropenem (about 2%), We can assume, that interactions with other medications can not be.

Meronem administered during the administration of other drugs, while it not noted any adverse pharmacological interactions.

Meronem may reduce levels of valproic acid in serum. Some patients may be below the therapeutic level is reached.

However, specific data on possible drug interactions there.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 4 year.

It is recommended for I / injections and infusions used freshly prepared solution Meronema, however diluted Meronem retains satisfactory efficacy when stored at room temperature (above 25 ° C) or in the refrigerator (at 4°C) in terms of, indicated in table.

The solution should not be frozen Meronema.