Мезонекс

General characteristics. Structure:

Active ingredient: 500 mg or 1 g of a meropenem.

Excipients: sodium carbonate.

Pharmacological properties:

Pharmacodynamics. Мезонекс - the antibiotic of a class of karbapenem, is intended for parenteral use, is steady against dehydropeptidase-1 (DGP-1) of the person, does not demand additional administration of DGP-1 inhibitor. Мезонекс has bactericidal effect due to impact on synthesis of a cell wall of bacteria. Powerful bactericidal action of a meropenem against a wide range of aerobic and anaerobic bacteria is explained by high ability of a meropenem to get through a cell wall of bacteria, the high level of stability to the majority β-лактамаз and considerable affinity to the proteins, connecting penicillin (P,CP). The Minimum Bactericidal Concentration (MBC) are usually same, as well as the minimum inhibiting concentration (MIC). For 76% of the tested species of bacteria the ratio of MBK/MIK was 2 or less.

Meropenem is stable in tests of definition of sensitivity of the activator. Meropenem acts synergistically with various antibiotics. Also Meropenem has post-antibiotic effect.

The range of antibacterial activity includes:

Aerobic gram-positive bacteria: Bacillus spp., Corynebacterium diphtheriae, Enterococcus (liquifaciens, avium), Listeria monocytogenes, Lactobacillus spp., Nocardia asteroides, Staphylococcus aureus (a penicillinase - negative and positive), Stafilokokki koagulozo-negative including, Staphylococcus (aprophyticus, capitis, cohnii, xylosus. warneri, hominis, simulans, intermedius, sciuri, lugdunensis), Streptococcus pneumoniae (sensitive and steady against penicillin). Streptococcus (agalactiae, pyogenes, equi, bovis, mitis, mitior, milleri, sanguis, viridans, salivarius, morbillorum), group G Streptococci, Streptococci of group F, Rhodococcus equi.

Aerobic gram-negative bacteria: Achromobacter xylosoxidans, Acinetobacter (anitratus, lwoffii, baumannii), Aeromonas (hydrophila, sorbria, caviae), Alcaligenes faecalis, Bordetella bronchiseptica, Brucella melitensis, Campylobacter (coli, jejuni), Citrobacter (freundii, diversus, koseri, amalonaticus), Enterobacter (aerogenes, agglomerans, cloacae, sakazakii), Escherichia (coli, hermannii), Gardnerella vaginalis, Haemophilus influenzae (включаяβ-лактамаза-позитивныеи ampicillin - resistant strains), Haemophilus (parainfluenzae, ducreyi), Helicobacter pylori, Neisseria (meningitidis, gonorrhoeae) (including strains β-laktamaza-pozitivny, steady against penicillin and a spektinomitsin), Hafnia alvei, Klebsiella (pneumoniae, aerogenes, ozaenae, oxytoca), Moraxella catarrhalis, Morganella morganii, Proteus (mirabilis, vulgaris, penneri), Providencia (rettgeri, stuartii, alcalifaciens), Pasteurella multocida, Plesiomonas shigelloides, Pseudomonas (putida, alcaligenes, Burkholderia (Pseudomonas) cepacia, fluorescens, stutzeri, pseudomallei, acidovorans), Salmonella spp., vklyuchayasalmonella enteritidis/typhi, Serratia (marcescens, liquefaciens, rubidaea), Shigella (sonnei, flexneri, boydii, dysenteriae), Vibrio (cholerae, parahaemolyticus, vulnificus), Yersinia enterocolitica.

Anaerobic bacteria: Actinomyces (odontolyticus, meyeri), Bacteroides-Prevolella-Porphyromonas spp., Bacteroides (caccae, fragilis, vulgatus, variabilis, pneumosintes, coagulans, uniformis, distasonis, ovatus, thetaiotaomicron, eggerthii, capsillosis, gracilis), Prevotella (buccalis, corporis, melaninogenica, intermedia, bivia, splanchnicus, aoralis, disiens, rumenicola, ureolyticus, oris, buccae, denticola, levii), Porphyromonasa saccharolyticus, Bifido bacterium spp. Bilophilia wadsworthia, Clostridium (perfringens, bifermentans, ramosum, sporogenes, cadaveris, sordellii, butyricum, clostridiiformis, innocuum, subterminale, tertium), Eubacterium (lentum, aerofaciens), Fusobacterium (mortiferum, necrophorum, nucleatum, varium), Mobiluncus (curtisii, mulieris), Peptoniphilus asaccharolyticus, Peptostreptococcus (anaerobius, micros, saccharolyticus, magnus, prevotii), Peptococcus (saccharolyticus, asaccharolyticus), Propionibacterium (acnes, avidium, granulosum).

Strains of bacteria for which the acquired resistance can be a problem: Enterococcus faecium, Acinetobacter spp., Burkholderia spp. and Pseudomonas aeruginosa

The microorganisms steady by the nature: Stenotrophomonas maltophilia and Legionella spp.

Other microorganisms: Chlamydophila pneumoniae, Chlamydophila psittaci and Micoplasma pneumoniae.

Pharmacokinetics. Intravenous administration within 30 min. one dose of Mezoneks results in peak concentration in a blood plasma equal 23 mkg/ml in the range of doses of 14-26 mkg/ml for a dose of 500 mg, 49 mkg/ml in the range of doses of 39 - 58 mkg/ml for a dose of 1 g and 115 mkg/ml for a dose of 2 g. The intravenous bolyusny injection of one dose of Mezoneks within 5 min. results in peak concentration in the plasma equal to about 45 mkg/ml in range of doses of 18 - 65 mkg/ml for a dose of 500 mg and 112 mkg/ml in the range of doses of 83-140 mkg/ml - for a dose of 1 g.

In 6 h after intravenous administration of 500 mg the level of a meropenem in a blood plasma decreases to values of 1 mkg/ml and below. At repeated introduction of a meropenem at an interval of 8 and 6 h for a dosage of 500 mg and 1 g according to, to patients with normal function of kidneys of cumulation of drug it is not observed. At patients with normal function of kidneys the elimination half-life makes about 1 h. The average volume of distribution makes about 0,25 l/kg (11-27 l). Linkng with proteins of plasma about 2% also does not depend on concentration.

Meropenem well gets into the majority of fabrics and liquids of an organism, including lungs, a bronchial secret, bile, cerebrospinal fluid, gynecologic fabrics, skin, a fascia, a muscle, and peritoneal exudate.

Meropenem is metabolized by hydrolysis of a β-laktamny ring, making microbiological inactive metabolite. In vitro meropeny shows reduced sensitivity to hydrolysis by dehydropeptidase - the I (DGP-I) person in comparison with imipenemy therefore there is no need for combined use of DGP-I inhibitors.

Meropenem is excreted, generally by kidneys; about 70% (50 - 75%) of a dose are removed in not changed look during 12 h. The remained 28% are removed as microbiological inactive metabolite. With a stake only about 2% of a dose are removed. The dosed renal clearance and action of a probenitsid are shown that Meropenem undergoes both filtering and canalicular secretion.

Pharmakokinetka Meropenema at pediatric patients at the age of 2 years is also more senior is generally similar to pharmacokinetics at adult patients. The elimination half-life of Meropenem made about 1,5 h at pediatric patients aged from 3 months up to 2 years. Pharmakokinetka of drug is linear in the range of doses from 10 to 40 mg/kg.

Pharmacokinetics researches at patients with a renal failure showed that the renal failure leads to increase in average concentration of drug in urine and to longer elimination half-life of Meropenem. Increases in average concentration in urine by 2,4 times at patients with moderate insufficiency (CrCL of 33-74 ml/min.), increases by 5 times at patients with heavy insufficiency (CrCL of 4-23 ml/min.) and increases by 10 times at patients on a hemodialysis were observed (CrCL <2 ml/min.) in comparison with healthy participants of a research (CrCL> of 80 ml/min.). Average concentration in urine of microbiological inactive metabolite with disclosure of a ring was also considerably increased at patients with a renal failure.

Correction of a dose is recommended for patients with a renal failure of average and heavy degree.

Meropenem is brought at a hemodialysis with clearance during a hemodialysis about 4 times higher, than at anuretic patients.

Pharmacokinetic researches of healthy subjects of advanced age (65-80 years) showed reduction of clearance of blood serum which is interconnected with reduction of clearance of creatinine in connection with age changes and reduction of not renal clearance. Patients of advanced age do not need correction of a dose, except cases of a renal failure of average and heavy degree.

Pharmacokinetics researches at patients with diseases of a liver showed that these pathological changes do not exert impact on pharmacokinetics of a meropenem.

Indications to use:

Meropenem is shown for treatment of the following infections of the adults and children called by one or more sensitive strains of the specified microorganisms:

— infections of lower parts of respiratory tracts, including pneumonia;

— infections of uric ways, including the complicated infections;

— intraabdominal infections;

— gynecologic infections, including puerperal infections;

— infections of skin and soft tissues;

— meningitis;

— sepsis;

— empirical treatment (including initial monotherapy) at suspicion of a bacterial infection at patients with a neutropenia.

Route of administration and doses:

The dosage and duration of therapy have to be established depending on type and weight of an infection and a condition of the patient.

Daily doses - 500 mg intravenously each 8 h are recommended at treatment of pneumonia, infections of urinary tract, gynecologic infections, such as an endometritis, infections of skin and structures of skin and 1 g intravenously each 8 h at treatment of hospital pneumonia, peritonitis, suspicion of a bacterial infection at patients with neutropenia symptoms, and also a septicaemia. At treatment of meningitis the recommended dose makes 2 g each 8 h.

At a renal failure with clearance of creatinine less than 51 ml/min. are required correction of the mode of dosing as follows:

Clearance of creatinine (ml/min.)	Dose (on the basis of unit of doses of 500 mg, 1 g)	Introduction frequency
26 - 50	One unit of a dose	each 12 h
10-25	0,5 units of a dose	each 12 h
<10	0,5 units of a dose	each 24 h

Meropenem is brought at a hemodialysis and haemo filtering. The recommended dose should be entered at the end of the procedure of a hemodialysis.

There are no established recommendations about a dosage for the patients who are on peritoneal dialysis.

For children aged from 3 months up to 12 years the recommended dose for intravenous administration makes 10-20 mg/kg each 8 h depending on type and weight of an infection, sensitivity of a pathogenic microorganism and a condition of the patient.

At children weighing more than 50 kg it is necessary to use dosages for adults. At meningitis the recommended dose makes 40 mg/kg each 8 h.

Correction of a dose is not required to patients of advanced age with normal renal function.

Correction of a dose is not required to patients with a liver failure.

Rules of preparation and administration of solutions. Мезонекс for intravenous bolyusny injections it is necessary to part with sterile water for injections (5 ml on 250 mg of a meropenem), at the same time concentration of solution makes about 50 mg/ml. Мезонекс for intravenous infusions it can be divorced with compatible infusional liquid (from 50 to 200 ml).

Мезонекс for intravenous use it can be entered in the form of an intravenous bolyusny injection within 3-5 min., or in the form of intravenous infusion within 15-30 min.

Features of use:

Use at pregnancy and feeding by a breast. It is contraindicated at pregnancy, in the period of a lactation.

Use at abnormal liver functions. Correction of a dose is not required to patients with a liver failure.

It is necessary to check carefully function of a liver during treatment by Mezoneks owing to possible development of hepatic toxicity (hepatic dysfunction with a cholestasia and a cytolysis).

Use for elderly patients. Correction of a dose is not required to patients of advanced age with normal renal function.

Use for children. It is contraindicated at children's age up to 3 months (efficiency and safety for this group of patients were not investigated).

For children aged from 3 months up to 12 years the recommended dose for intravenous administration makes 10-20 mg/kg each 8 h depending on type and weight of an infection, sensitivity of a pathogenic microorganism and a condition of the patient.

At children weighing more than 50 kg it is necessary to use dosages for adults. At meningitis the recommended dose makes 40 mg/kg each 8 h.

Special instructions. At Mezoneks's appointment for treatment of individual patients it is necessary to consider compatibility of this drug with antibacterial drug karbapenemy on the basis of such factors as severity of an infection, dominance of stability in comparison with other corresponding antibacterial drugs and a possibility of the choice against bacteria steady against karbapeny.

As well as in a case with all beta лактамными antibiotics, it is reported about heavy and sometimes fatal allergic reactions.

The patients having in the anamnesis hypersensitivity to karbapenema, penicillin or another beta лактамным to antibiotics can show hypersensitivity to Meropenem. Before to begin therapy using Mezoneks, it is necessary to request exact data of rather previous allergic reactions to a beta laktamnye antibiotics.

In case of heavy allergic reaction, it is necessary to stop administration of medicine and to take the appropriate measures.

It is reported about an antibiotic - the associated colitis and pseudomembranous colitis at use of almost all antibacterial drugs (including Meropenem) and can vary on intensity from lungs to life-threatening forms. Therefore, it is important to consider this diagnosis at patients with complaints to diarrhea in time or after Mezoneks's introduction.

It is necessary to consider the termination of therapy using Mezoneks and performing special treatment concerning the toxin produced by Clostridium difficile. It is not necessary to appoint the medicines oppressing a peristaltics.

It is seldom reported about paroxysm cases during treatment using karbapenem, including Mezoneks.

It is necessary to check carefully function of a liver during treatment by Mezoneks owing to possible development of hepatic toxicity (hepatic dysfunction with a cholestasia and a cytolysis)

Drug use by patients with a liver disease: during treatment by Mezoneks it is necessary to control function of a liver at patients with earlier existing disturbances of a liver. Correction of a dose is not required.

During treatment by Mezoneks positive direct or indirect tests of Koombs can come to light. The concomitant use of Mezoneks and valproyevy acid / Valproatum of sodium is not recommended.

Use in pediatrics. Efficiency and portability of drug at children aged up to 3 months was not estimated in this connection use of drug for children is not recommended is younger than this age. There is no experience of use of drug for children with abnormal liver functions and kidneys, at patients with a neutropenia, or with primary and secondary immunodeficience.

Features of influence of medicine on ability to manage the vehicle or potentially dangerous mechanisms

Special researches of influence of Meropenem on ability to drive the car and other equipment were not conducted.

Side effects:

Often:

— trombotsitemiya;

— headache;

— nausea, vomiting, diarrhea;

— increase in concentration of alaninaminotranspherase, aspartate aminotransferase, an alkaline phosphatase, lactate dehydrogenase and γ-glutamiltransferaza in blood serum;

— rash, itch;

— an inflammation and pain in an injection site.

Infrequently:

— candidiasis of an oral cavity and vaginal candidiasis;

— eosinophilia, thrombocytopenia, leukopenia, neutropenia;

— paresthesias;

— increase in concentration of bilirubin in blood serum;

— small tortoiseshell;

— thrombophlebitis.

Seldom:

— spasms;

— agranulocytosis.

Very seldom:

— hemolitic anemia;

— Quincke's edema, displays of an anaphylaxis;

— pseudomembranous colitis;

— multiformny erythema, Stephens-Johnson's syndrome and toxic epidermal necrolysis;

— anorexia;

— hyperexcitability, agitation, concern, depression, hallucinations, uneasiness, sleeplessness;

— peripheral hypostases, dysuria, hamaturia, renal failure;

— reversible thrombocytosis, eosinophilia, thrombocytopenia, leukopenia;

— Quincke's edema;

— spasms;

— epileptiform attacks;

— cholestatic hepatitis, hyperbilirubinemia, jaundice;

— cardiac standstill, heart failure, tachycardia, bradycardia, asthma, decrease or increase in the ABP, myocardial infarction, thrombembolia of a pulmonary artery.

Interaction with other medicines:

Probenetsid competes with meropenemy for active canalicular secretion, inhibiting renal excretion and causing increase in an elimination half-life and concentration of a meropenem in plasma. As efficiency and duration of action of Mezoneks entered without probenetsid are adequate, joint introduction of a probenetsid with Mezoneks is not recommended.

Possible impact of Meropenem on linkng of other drugs with proteins or metabolism was not studied. Meropenem's linkng with proteins low (about 2%), is supposed that the interaction with other drugs based on replacement from proteins of plasma should not be.

Meropenem can reduce valproic acid level in blood serum. Simultaneous use of valproyevy acid / Valproatum of sodium with Meropenem is not recommended.

The concomitant use of Meropenem with warfarin can strengthen its anticoagulating effect. Strengthening of anticoagulating effect can vary depending on the masked infection, age and the general condition of the patient in such a way that it is difficult to estimate influence of an antibiotic on increase in INR (The international normalized relation). It is recommended that INR was often checked in time and right after a concomitant use of antibiotics with peroral anticoagulating drugs.

Meropenem's use during reception of other drugs was not followed by development of adverse pharmacological interactions. However there are no specific data on possible medicinal interactions.

Contraindications:

— hypersensitivity to meropeny, to components of drug and another beta лактамным to antibiotics;

— pregnancy and period of a lactation;

— children's age up to 3 months (efficiency and safety for this group of patients were not investigated).

With care: co-administration of Mezoneks with potentially nefrotoksichny drugs. To the persons with gastrointestinal diseases who especially have colitis.

Overdose:

The accidental overdose is possible during treatment, especially at treatment of patients with an impaired renal function.

Symptoms: strengthening of side effects of drug.

Treatment: symptomatic. Patients with normal function of kidneys have a bystry removal of drug to urine. At patients with renal disturbances the hemodialysis is effective.

Storage conditions:

To store in dry protected from light and the place, unavailable to children, at a temperature not over 25 ºС. A period of storage - 2 years.

Issue conditions:

According to the recipe

Packaging:

Bottles glass (1) - boxes cardboard.
Bottles glass (50) - boxes cardboard.