Меропенабол®

General characteristics. Structure:

Active ingredient: 0,5 g or 1,0 g of a meropenem trihydrate (in recalculation in meropeny).

Excipient: sodium carbonate.

Pharmacological properties:

Pharmacodynamics. Meropenem - an antibiotic from group of karbapenem for parenteral use, interacts with receptors - specific penitsillinsvyazyvayushchy proteins on a cytoplasmic membrane surface, suppresses transpeptidase, slows down synthesis of peptidoglikan of a cell wall (owing to structural similarity) that as a result causes its damage and death of bacteria. It is steady against renal dehydropeptidase-1, works bakteritsidno, easily gets through a cell wall of bacteria, it is steady against action of the majority beta лактамаз, has high affinity to penitsillinsvyazyvayushchy proteins (PBPs). Among known beta лактамных antibiotics has the highest activity concerning the majority of aerobic and anaerobic gram-positive and gram-negative microorganisms.

It is active concerning gram-positive aerobes: Bacillus spp., Corynebacterium diphtheriae, Enterococcus liquifaciens, Enterococcus avium, Enterococcus faecalis, Listeria monocytogenes, Lactobacillus spp., Nocardia asteroides, Staphylococcus aureus (including penitsillinazoprodutsiruyushchy), Staphylococcus spp. (koagulazo-negative), including Staphylococcus saprophyticus, Staphylococcus capitis, Streptococcus pneumoniae (including strains steady against penicillin), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus mitis, Streptococcus viridans, Streptococcus salivarius, Streptococcus morbillorum, Streptococcus spp. (groups G and 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 amalonaticus, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae (including the beta lactamazoproducing and ampitsillinoustoychivy strains), Haemophilus parainfluenzae, Haemophilus ducreyi, Helicobacter pylori, Neisseria meningitidis, Neisseria gonorrhoeae (including strains producers beta лактамаз, steady against penicillin and a spektinomitsin), Hafhia alvei, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella catarrhalis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia alcalifaciens, Pasteurella multocida, Pseudomonas shigelloides, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas alcaligenes, Burkholderia cepacia, Pseudomonas fluorescens, Pseudomonas stutzeri, Stenotrophomonas, Salmonella spp., including Salmonella typhi, Serratia marcescens, Serratia liquifaciens, Serratia spp., Shigella sonnei, Shigella flexneri, Shigella dysenteria, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Yersinia enterocolitica.

Anaerobic bacteria: Actinomyces israelii, Bacteroides spp. (including Bacteroides fragilis, Bacteroides vulgatus, Bacteroides variabilis, Bacteroides pneumosintes, Bacteroides coagulans, Bacteroides uniformis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron), Prevotella spp. (including Prevotella melaninogenica, Prevotella buccae, Prevotella denticola, Prevotella levii), Porphyromonas spp. (including Porphyromonas asaccharolyticus), Bifidobacterium spp. Clostridium perfringens, Clostridium difficile, Clostridium sporogenes, Clostridium cadaveris, Clostridium sordellii, Clostridium butyricum, Clostridium clostridiiformis, Clostridium tetani, Eubacter lentum, Eubacter aerofaciens, Fusobacterium mortiferum, Fusobacterium necrophorum, Mobiluncus curtisii, Mobiluncus mulieris, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus saccharolyticus, Peptococcus magnus, Peptococcus prevotii, Propionibacterium acne, Propionibacterium avidium, Propionibacterium granulosum.

Pharmacokinetics. At intravenous (in) introduction of 250 mg within 30 min. the maximum concentration) _Cmax - 11 mkg/ml, for a dose of 500 mg - 23 mkg/ml, 1 g - 49 mkg/ml (there is no absolute pharmacokinetic proportional dependence on the entered dose for _Cmax and AUC). At increase in a dose from 0:25 to 2 g the clearance decreases from 287 to 205 ml/min. At in bolyusny introduction within 5 min. 500 mg _{of Cmax} - 52 mkg/ml, 1 g - 112 mkg/ml. Communication with proteins of plasma of 2%.

Well gets into the majority of fabrics and liquids of an organism, including into SMZh of patients with bacterial meningitis, reaching the concentration exceeding demanded for suppression of the majority of sensitive bacteria (bactericidal concentration are created in 0.5-1.5 h after the beginning of infusion). In insignificant quantities gets into breast milk.

Is exposed to insignificant metabolism in a liver with formation of the only inactive metabolite. The elimination half-life (Т½) - 1 h, at children up to 2 years is 1.5-2.3 h. In the range of doses of 10-40 mg/kg at adults and children linear dependence of pharmacokinetic parameters is observed. Does not kumulirut.

It is removed by kidneys of 70% in not changed look during 12 h. The concentration of a meropenem in urine exceeding 10 mkg/ml is maintained during 5 h after introduction of 500 mg. At patients with a renal failure the clearance correlates with the clearance of creatinine (CC). At elderly patients decrease in clearance of a meropenem correlates with age decrease in KK; Т½ - 1.5 h.
It is removed at a hemodialysis.

Indications to use:

The infectious and inflammatory diseases caused by sensitive activators: lower respiratory tract infections (including pneumonia, including hospital; the infections caused by a pyocyanic stick), abdominal infections (the complicated appendicitis, peritonitis, a pelviperitonitis). pyelonephritis, a pyelitis, infections of skin and soft tissues (including the ugly face, impetigo for the second time infected a dermatosis), dysentery, an endocarditis, bacterial meningitis, sepsis, inflammatory diseases of bodies of a small pelvis (including an endometritis), suspicion of a bacterial infection at adults with febrile episodes against the background of a neutropenia (empirical treatment).

Route of administration and doses:

Meropenabol has to is entered in the form of an intravenous bolyusny injection within not less than 5 minutes, or in the form of intravenous infusion within 15-30 minutes.

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

The following daily doses are recommended:
Adults: To 500 mg there are intravenously each 8 hours at treatment of pneumonia, infections of an urinogenital path, gynecologic infections, such as an endometritis, and inflammatory diseases of pelvic bodies, infections of skin and soft tissues.

To 1 g patients have intravenously each 8 hours at treatment of hospital pneumonia, peritonitis, suspicions of a bacterial infection with a neutropenia, and also a septicaemia.

At treatment of meningitis the recommended dose makes 2 g each 8 hours.

At a chronic renal failure the dose is adjusted depending on the clearance of creatinine (CC): at KK of 26-50 ml / мин-по 0.5-1 g 2 times in knots, 10-25 ml/min. - on 250-500 mg 2 times a day, less than 10 ml/min. - on 500 mg of 1 times a day.

Meropenem it is removed at a hemodialysis. If long treatment is required it is recommended that dose unit (is defined depending on type and weight of an infection) was entered at the end of the procedure of a hemodialysis to recover effective concentration in plasma.

Children: aged from 3 months up to 12 years the recommended dose for intravenous administration makes 10-20 mg/kg each 8 hours 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 hours. Meropenabol is not recommended for use for children 3 months are younger. There is no experience of use for children with an abnormal liver function and kidneys.

Preparation of solutions. For intravenous bolyusny injections Meropenabol has to get divorced sterile water for injections (K) of ml on 500 mg of a meropenem). It provides concentration of solution of 50 mg/ml.

For intravenous infusions Meropepabol to get divorced sterile water for injections or compatible infusional liquid and then still compatible infusional liquid (50-200 ml).

Meropenabol is compatible to the following infusional liquids:
- 0,9% of sodium chloride for in/in infusions;
- 5% or 10% of Dextrosum for in/in infusions;
- 5% of Dextrosum for in/in infusions from 0,02% of sodium bicarbonate;
- 0,9% of sodium chloride and 5% of Dextrosum for in/in infusions;
- 5% of Dextrosum from 0,225% of sodium of chloride for in/in infusions;
- 5% of Dextrosum from 0,15% of potassium chloride for in/in infusions;
- Mannitolum of 2,5% and 10% for in/in infusions.

Meropenabol should not mix up with the solutions containing other drugs.

Features of use:

The patients having in the anamnesis hypersensitivity to karbapenema, penicillin or other beta лактамным to antibiotics can show hypersensitivity to meropeny.

Treatment of patients with diseases of a liver has to be carried out under careful control of activity of "hepatic" transaminases and concentration of bilirubin.

In the course of treatment development of stability of activators in this connection prolonged treatment is carried out under constant control of distribution of resistant strains is possible. At the persons with complaints to a GIT who especially have colitis it is necessary to consider a possibility of development of pseudomembranous colitis (the toxin produced by Clostridium difficile is one of the main reasons for the colitis connected with antibiotics), as which first symptom development of diarrhea of a pas a treatment background can serve.

At monotherapy of the known or suspected lower respiratory tract infection of a heavy current caused by Pseudomonas aeruginosa regular definition of sensitivity of the activator is recommended.

Side effects:

From the alimentary system: pains in epigastric area, nausea, vomiting, diarrhea, cholestatic hepatitis, a hyperbilirubinemia, increase in activity of "hepatic" transaminases and an alkaline phosphatase, lactate dehydrogenase, it is rare – oral cavity candidiasis, pseudomembranous colitis.

From cardiovascular system: takhi-or bradycardia, decrease or increase in arterial pressure, development or aggravation of heart failure, unconscious states, myocardial infarction, thrombembolia of branches of a pulmonary artery, cardiac standstill.

From an urinary system: a dysuria, hypostases, a renal failure (a giperkreatininemiya, increase in concentration of urea in plasma), a hamaturia.

Allergic reactions: skin itch, skin rash, small tortoiseshell, multiformny exudative erythema, Quincke's disease, acute anaphylaxis.

From a nervous system: headache, paresthesias, sleeplessness, hypererethism, uneasiness, depression, disturbance of consciousness, hallucination, epileptiform attacks, spasms.

From laboratory indicators: an eosinophilia, a neutropenia, a leukopenia, it is rare – an agranulocytosis, reversible thrombocytopenia, decrease in partial tromboplastinovy time.

Local reactions: an inflammation, thrombophlebitis, morbidity in an injection site.

Others: positive direct or indirect tests of Koombs, anemia, диспноэ, vaginal candidiasis.

Interaction with other medicines:

Let's combine from 0,9% solution of sodium of chloride, 5% or 10% solutions of a dextrose, 5% solution of a dextrose and 0,02% solution of Natrii hydrocarbonas, 0,9% solution of sodium of chloride and 5% solution of a dextrose, 5% dextrose solution from 0,225% of sodium chloride, 5% dextrose solution from 0,15% of potassium chloride, 2,5% and 10% Mannitolum solution.

Compatibility of a meropenem with other medicines, except listed above, is not established. Therefore meropeny and its solutions it is not necessary to mix or add to the solutions containing other medicines.

The medicines blocking canalicular secretion slow down removal and increase concentration of a meropenem in plasma.

Contraindications:

Hypersensitivity, including to others beta лактамным to antibiotics; it is not applied at children up to 3 months (efficiency and safety are not established).
 
Safety of use during pregnancy is not defined. For the period of treatment it is necessary to stop breastfeeding.

Overdose:

The accidental overdose is possible during treatment, especially at patients with an impaired renal function. Treatment in case of overdose has to be symptomatic. Normal there is a bystry elimination of drug at a hemodialysis.

Storage conditions:

The list B in dry protected from light and the place, unavailable to children, at a temperature not above 25 °C.

It is recommended to apply the freshly cooked solution of Meropenabol however divorced meropeny to intravenous injections and infusions can keep the activity within 6 hours at storage of solution at a temperature not above 25 °C and 36 watch if to store solution at a temperature not above 5 °C. 

Not to freeze solution of a meropenem!

Issue conditions:

According to the recipe

Packaging:

0,5 g or 1,0 g of active agent in bottles glass.

1 bottle with drug together with the application instruction is placed in a pack from a cardboard.