Meropenem time. for infection 0,5; 1,0 No. 1

General characteristics. Structure:

Active ingredient: meropenem; 1 bottle contains a meropenem trihydrate in terms of 0,5 g or 1,0 g of a meropenem anhydrous; excipient: sodium carbonate bezvodnyy.osnovny physical and chemical properties: crystal powder white or with slightly yellowish shade of color.

Pharmacological properties:

Pharmacodynamics. Meropenem is a karbapenemovy antibiotic for parenteral use, rather stable to effect of dehydropeptidase-1 (DHP-1) of the person therefore does not demand addition of DHP-1 inhibitor.
Meropenem has bactericidal effect by intervention in the vital synthesis of walls of a bacterial cell. Ease with which it gets into walls of a bacterial cell, high level of stability to all serinovy beta lactamelements and the expressed affinity to the proteins connecting penicillin (RVR) explain strong bactericidal action of a meropenem against a wide range of aerobic and anaerobic bacteria. The minimum bactericidal concentration (MVS) usually same, as well as minimum inhibiting concentration (MIC). For 76% of bacteria MVS ratio: MIC made 2 and less. Meropenem is stable in sensitivity tests. In vitro tests specify what meropeny works synergy with different antibiotics. As in vitro and in vivo was shown, meropeny has post-antibiotic effect.
Referring to pharmacokinetics and a ratio of clinical and microbiological results concerning diameter of a zone and the minimum inhibiting concentration (MIC) for microorganisms, the uniform complex of criteria of sensitivity to meropeny is recommended.
 Categories Assessment Method
 Diameter of a zone (mm) Critical points of MIC (mg/ml)
Sensitivity ≥ 14 ≤ 4
Intermediate level  12-13 8
Resistance ≤ 11 ≥ 16
The antibacterial range of a meropenem of in vitro includes the majority of clinically significant gram-positive and gram-negative, aerobic and anaerobic strains of bacteria, as shown below.
Gram-positive aerobes:
Bacillus spp., Corynebacterium diphteriae, Enterococcus faecalis, Enterococcus liquifaciens, Enterococcus avium, Listeria monocytogenes, Lactobacillus spp., Nocardia asteroids, Staphylococcus aureus (positive and negative to a penicillinase), Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus warneri, Staphylococcus hominis, Staphylococcus simulans, Staphylococcus intermedins, Staphylococcus sciuri, Staphylococcus lugdunensis, Streptococcus pneumoniae (sensitive and resistant to penicillin), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus mitis, Streptococcus mitior, Streptococcus milleri, Streptococcus sanguis, Streptococcus viridans, Streptococcus salivarius, Streptococcus morbillorum, Streptococcus Group G, Streptococcus Group F, Rhodococcus equi.
Gram-negative aerobes:
Achromobacter xylosoxidans, Acinetobacter anitratus, Acinetobacter Iwoffii, Acinetobacter baumannii, Aeromonas hydrophila, Aeromonas sorbria, Aeromonas caviae, Alcaligenes faecalis, Bordetella ■bronchiseptica, Brucella melitensis, Campylobacter coli, Campylobacter jejuni, Citrobacter freundii, Citrobacter diversus, Citrobacter koseri, Citrobacter amalonaticus, Enterobacter aerogenes,
Enterobacter (Pantoea) aglomeran, Enterobcter cloacae, Enterobacter sakazakii, Escherichia coli, Escherichia hermannii, Gardnerella vaginalis, Haemophilus influenzae (including positive to a beta laktamaze and strains, resistant to ampicillin), Heamophilus parainfluenzae, Heamophilus ducreyi, Helicobacter pylori, Neisseria meningitides, Neisseria gonorrhoeae (including positive to beta lactamelements, resistant to penicillin and strains, resistant to a spektinomitsin), Hafnia alvei, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Proteus penneri, Providencia rettgeri, Providencia stuartii, Providencia alcalifaciens, Pasteurella multocida, Plesiomonas shigelloides, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas alcaligenes, Burkholderia (Pseudomonas) cepacia, Pseudomonas flourescens, Pseudomonas stutzeri, Pseudomonas pseudomallei, Pseudomonas acidovorans, Salmonella spp., vklyuchayuch of Salmonella enteritidis/typhi, Serratia marcescens, Serratia liquefaciens, Serratia rubidaea, Shigella sonnei, Shigella flexneri, Shigella boydii, Shigella dysenteriae, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Yersinia enterocolitica.
Anaerobic bacteria:
Actinomyces odontolyticus, Actinomyces meyeri, Bacteroides-Prevotella-Porphynomonas spp., Bacteroides fragilis, Bacteroides vulgatus, Bacteroides variabilis, Bacteroides pneumosintes, Bacteroides coagulans, Bacteroides uniformis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides eggerthii, Bacteroides capsillosis, Prevotella buccalis, Prevotella corporis, Bacteroides gracilis, Prevotella melaninogenica, Prevotella intermedia, Prevotella bivia, Prevotella splanchnicus, Prevotella oralis, Prevotella disiens, Prevotella rumenicola, Bacteroides ureolyticus, Prevotella oris, Prevotella buccae, Prevotella denticola, Bacteroides levii, Porphyromonas asaccharolytica, Bifidobacterium spp. Bilophila wadsworthia, Clostridium perfringens, Clostridium bifermentalis, Clostridium ramosum, Clostridium sporogenes, Clostridium cadaveris, Clostridium sordellii, Clostridium butyricum, Clostridium clostridiiformis, Clostridium, innocuum, Clostridium subterminale, Clostridium tertium, Eubacterium lentum, Eubacterium aerofaciens, Fusobacterium mortiferum, Fusobacterium necrophorum, Fusobacterium nucleatum, Fusobacterium varium, Mobiluncus curtisii, Mobiluncus mulieris, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus saccharolyticus, Peptococcus saccharolyticus, Peptostreptococcus asaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus prevotii, Propionibacterium acnes, Propionibacterium aidum, Propionibacterium granulosum.
Stenotrophomonas maltophilia, Enterococcus faecium and staphylococcus, resistant to Methicillinum as it was revealed, are resistant to meropeny.

Pharmacokinetics. After intravenous administration, depending on a dose (0,5 or 1 g) and a way of application (bolyusno or kapelno), the maximum value of concentration of drug in blood serum (Cmax) makes 23 mkg/ml, 45 mkg/ml, 49 mkg/ml and 112 mkg/ml respectively. Contacts proteins of plasma for 2%. Easily gets into various tissues and liquids of a human body (including spinal), bactericidal concentration are reached in 0,5 - 1,5 hours after introduction. Is exposed to insignificant biotransformation in a liver with formation of the only metabolite (pharmacological inactive). The elimination half-life of drug (T1/2) makes 1 hour. It is excreted, generally by kidneys (more than 70% are removed in not changed look). At a renal failure the plasma clearance of a meropenem is directly proportional to extent of decrease in clearance of creatinine. Pharmacokinetics of a meropenem at children same, as well as at adults. A drug elimination half-life at children under 2 years about 1,5 - 2,3 hours, at the same time note linear dependence "concentration - a dose" in the range of doses of 10 - 40 mg/kg. At elderly patients the clearance of a meropenem decreases, it correlates with decrease in clearance of the creatinine connected with age.
The clearance of a meropenem at patients with a renal failure is connected with clearance of creatinine. Therefore drug dose adjustment is necessary for patients with the increased clearance of creatinine. The pharmacokinetics of a meropenem at patients with diseases of a liver does not change.

Indications to use:

Treatment of the infections caused sensitive to meropeny by bacteria:
• pneumonia, including hospital;
• infections of urinary tract;
• intraabdominal infections;
• gynecologic infections, such as endometritis;
• infections of skin and soft tissues;
• meningitis;
• septicaemia;
• empirical therapy at suspicion of a bacterial infection at adults with a febrile neutropenia, as monotherapy or in a combination with anti-virus or antifungal drugs.
Meropenem apply in the form of monotherapy or as a part of the combined treatment with other antimicrobic means at treatment of polymicrobial infections (for example, cystous fibrosis, persistent infections of the lower respiratory tracts).

Route of administration and doses:

Adults
The dosage and duration of therapy establish depending on type, weight of an infection and a condition of the patient. The recommended daily dose makes:
At treatment of pneumonia, infections of urinary tract, gynecologic infections, such as an endometritis, infections of skin and soft tissues - 500 mg of Meropenem each 8 hours.
At treatment of hospital pneumonia, peritonitis, the suspected infections at patients with a neutropenia, a septicaemia - 1000 mg of Meropenem each 8 hours.
At cystous fibrosis the recommended dose makes 2 g each 8 hours.
At meningitis the recommended dose makes 2 g each 8 hours.
As well as in a case with other antibiotics, it is necessary to be especially careful at use of a meropenem as monotherapy at seriously ill patients of patients with the known or suspected infection of Pseudomonas aeruginosa of the lower respiratory tracts.
At treatment of an infection of Pseudomonas aeruginosa it is necessary to carry out the sensitivity test regularly.
The scheme of a dosage for adult patients with insufficiency of renal function.
At patients with clearance of creatinine lower than 51 ml/min. a dose should be lowered according to the scheme provided below:
Clearance of creatinine (ml/min.) the Dose (on the basis of unit of doses of 500 mg, 1 g, 2 g) Frequency
26-50 one unit of a dose each 12 hours
10-25 half of unit of a dose each 12 hours
<10th half of unit of a dose each 24 hours
Meropenem is brought by means of a hemodialysis; if long treatment by Meropenem is necessary, it is recommended to enter dose unit (depending on type and weight of an infection) after completion of the procedure of a hemodialysis to recover therapeutic effective plasma concentration.
There is no experience of use of Meropenem for the patients who are on peritoneal dialysis.
Dosage at patients with a liver failure
Dose adjustment is not required.
Elderly patients
For elderly patients with normal function of kidneys or indicators of clearance of creatinine higher than 50 ml/min. dose adjustment is not required.
Children.
For children aged from 3 months up to 12 years the recommended dose makes 10-20 mg/kg each 8 hours, depending on type and weight of an infection, sensitivity of a pathogen and a condition of the patient. At children with body weight more than 50 kg it is necessary to use a dose for adults. For children aged from 4 years up to 18 years with cystous fibrosis, and also apply doses within 25 - 40 mg/kg to treatment of a sharpening of persistent infections of the lower respiratory tracts each 8 hours. At meningitis the recommended dose makes 40 mg/kg each 8 hours.
Route of administration.
Before use to stir up the prepared solution.
Meropenem it is possible to enter intravenously bolyusno within 5 min. or intravenously infusionally within 15-30 min.
Meropenem for use it is intravenously bolyusno necessary to dissolve in sterile water for injections (5 ml on 250 mg of a meropenem) owing to what receive concentration of 50 mg/ml. The prepared solution transparent and colourless or light yellow color. Meropenem for intravenous infusion it is possible to prepare by means of compatible liquids for infusions (50 - 200 ml).
Meropenem is compatible to such liquids for infusions:
• 0,9% chloride sodium solution;
• 5% or 10% glucose solution;
• 5% glucose solution from 0,02% of sodium bicarbonate;
• 5% glucose solution from 0,9% of sodium chloride;
• 5% glucose solution from 0.225% chloride sodium solution;
• 5% glucose solution from 0,15% chloride potassium solution;
• 2,5% or 10% Mannitolum solution.

Incompatibility.
Meropenem it is not necessary to mix or add to other medicines. As solvent apply only those medicines which are given in the section "Route of Administration and Doses".

Features of use:

There is a cross allergenicity between other karbapenema and beta лактамными antibiotics, penicillin and cephalosporins. Before therapy meropenemy it is necessary to conduct careful survey of rather previous reactions of hypersensitivity to a beta laktamnye antibiotics and to use drug with care at patients with such cases in the anamnesis. At emergence of allergic reaction on meropeny use of drug it is necessary to stop and resort to the relevant activities. At Meropenem's use for patients with a disease of a liver it is necessary to watch levels of transaminases and bilirubin carefully.
As well as in a case with other antimicrobic drugs, the excess growth of microorganisms, insensitive to an antibiotic, therefore each patient has to be under observation of the doctor a long time is possible.
Use for treatment of the infections caused by stafilokokka, resistant to Methicillinum is not recommended.
At treatment by Meropenem it was seldom reported about cases of developing of pseudomembranous colitis which severity can vary from easy to life-threatening. Therefore persons should appoint antibiotics with care with gastrointestinal complaints in the anamnesis, especially colitis.
It is important to pay attention to the diagnosis pseudomembranous colitis at patients who had a diarrhea at Meropenem's use. Though researches indicate that the toxin produced by Costridium difficile is one of the main reasons for the colitis connected using antibiotics, other reasons should be taken into account also. It is necessary to be careful at Meropenem's use together with potentially nephrotoxic drugs.
Ability to influence the speed of reactions at control of motor transport or work with other mechanisms. Data are absent, however Meropenem's influence on ability to drive the car or to work with mechanisms is not expected.

Side effects:

Meropenem, as a rule, is well had. Side reactions seldom demand the treatment termination. About serious side reactions it was reported very seldom. Applied such criteria to assessment of frequency of emergence of the undesirable phenomena: extended (≥ 1%, <10%), not widespread (≥ 0,1%, <1%) and very seldom widespread (≥ 0,01%, <0,1%).
Widespread
(≥ 1%, <10%) from the circulatory and lymphatic Thrombocytopenia systems
 From a nervous system Headache
 From outside
the alimentary system Nausea, vomiting, diarrhea, an abdominal cavity pain, increase in concentration of transaminases, an alkaline phosphatase, lactate dehydrogenase in serum
 From skin and hypodermic cellulose Rash, itch
 General frustration and condition of an injection site Inflammation, pain
Not widespread
(≥ 0,1%, <1%) from the circulatory and lymphatic Eosinophilia systems, thrombocytopenia
 Gepatobiliarny frustration Increase in concentration of bilirubin
Very seldom widespread
(≥ 0,01%, <0,1%) from a nervous system of the Spasm
Frequency is not established from the blood circulatory system and lymphatic system the Leukopenia, a neutropenia, an agranulocytosis, hemolitic anemia
 From immune system Quincke's disease, displays of an anaphylaxis
 From a nervous system Paresthesia
 From outside
alimentary system Pseudomembranous colitis
 From skin and hypodermic cellulose the Small tortoiseshell, Stephens's syndrome - Johnson, a multiformny erythema, a toxic epidermal necrolysis
 General frustration and condition of an injection site Thrombophlebitis, oral and vaginal candidiasis

Interaction with other medicines:

It is necessary to be careful at Meropenem's appointment along with potentially toxic drugs for kidneys.
Probenetsid competes with meropenemy rather tubular removal and, thus, oppresses renal secretion which leads to lengthening of half-life and increase in concentration of a meropenem in plasma. As force and duration of action of Meropenem entered without probenetsid, identical is not recommended to enter пробенецид and Meropenem at the same time.
Potential influence of Meropenem on binding of proteins other drugs or their metabolism was not studied.
Meropenem can reduce serumal concentration of valproic acid. At some patients these levels can reach subtherapeutic.
Meropenem was appointed along with other medicines without uniform undesirable pharmacological interaction (except a probenetsid about whom it is mentioned above).

Contraindications:

Hypersensitivity to drug.
Children's age up to 3 months.
Children with abnormal liver functions and kidneys.

Overdose:

Side effects after overdose correspond to characteristics of the side reactions described in the section "Side reactions". Symptomatic treatment; hemodialysis.
Use during pregnancy or feeding by a breast.
Meropenem it is not necessary to apply during pregnancy and feeding by a breast, except for cases when the expected advantage for mother exceeds potential risk for a fruit or the child.
In each case drug should be used under direct observation of the doctor. For treatment it is necessary to abstain from feeding by a breast.
Children.
Drug is not used to children aged up to 3 months and to children with abnormal liver functions and kidneys.
Experience of use for children with a neutropenia or primary or secondary immunodeficience is absent.

Storage conditions:

To store in the place protected from light at a temperature not above 20 °C. Not to freeze. To store in the place, unavailable to children.
It is recommended to apply freshly cooked solutions of Meropenem for in/in injections and infusions according to the conditions given in the table.
 The Duration (Hours) of Stability solvent at  a temperature up to 25 °C of 4 °C
Solvents (1-20 mg/ml) prepared with:
0,9% of sodium  chloride 8 48
5%  glucose 3 14
5% glucose and 0,225% of sodium  chloride 3 14
5% glucose and 0,9% of sodium  chloride 3 14
5% glucose and 0,15% of potassium  chloride 3 14
2,5% or 10% Mannitolum solution for intravenous infusion  3 14
10%  glucose 2 8
5% glucose and 0,02% of sodium
bicarbonate for intravenous infusions  2 8
In preparation time of solution it is necessary to apply standard aseptic techniques.
Before use to stir up the prepared solution.
All bottles are intended only for single application.

Period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

On 0,5 g or 0,1 g in bottles; on 1 bottle in a pack.