Borinem

General characteristics. Structure:

Active ingredient: 500 mg of a meropenem (in the form of a meropenem and sodium of a carbonate) in 1 bottle.

Pharmacological properties:

Pharmacodynamics. An antibiotic with a broad spectrum of activity from group of karbapenem for parenteral (intravenous) use, steady against dehydropeptidase-1 of the person. Has bactericidal effect due to influence on synthesis of a cell wall of bacteria. Ease of penetration through a cell wall of bacteria, high level of stability practically to all β-lactamelements and considerable affinity to penitsillinsvyazyvayushchy proteins (PSB), cause powerful bactericidal action of Borinem against a wide range of aerobic and anaerobic bacteria. Bactericidal concentration are usually close to its minimum overwhelming concentration (MOC). In in vitro tests it was established what meropeny possesses a synergism with antibiotics of group of glycopeptides, aminoglycosides, ftorkhinolona, nitroimidazoles. In in vitro tests and in vivo, it was established what meropeny has post-antibiotic effect.

The antibacterial range of a meropenem determined by in vitro includes practically all clinically significant gram-positive and gram-negative aerobic and anaerobic microorganisms.

Drug is active in the relation:

- aerobic gram-positive bacteria: Bacillus spp., Corynebacterium diphtheriae, Enterococcus liquifaciens, Enterococcus avium, Listeria monocytogenes, Lactobacillus spp. Nocardia asteroides, Staphylococcus aureus (which are lactamazoproducing and not producing strains), a coagualase - negative staphylococcus, including Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus warneri, Staphylococcus hominis, Staphylococcus simulans, Staphylococcus intermedius, Staphylococcus sciuri, Staphylococcus lugdenensis, Streptococcus pneumoniae (sensitive and steady to - to laktamny antibiotics), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus mitis, Streptococcus mitior, Streptococcus milleri, Streptococcus sanguis, Streptococcus viridans, Streptococcus salivarius, Streptococcus morbillorum, streptococci of 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 diversus, Citrobacter koseri, Citrobacter amalonaticus, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter sakazakii, Escherichia coli, Escherichia hermannii, Gardnerella vaginalis, Haemophilus influenzae (including - the lactamazoproducing strains), Haemophilus parainfluenzae, Haemophilus ducreyi, Helicobacter pylori, Neisseria meningitidis, Neisseria gonorrhoeae (including - the lactamazoproducing strains and spektinomitsin-resistant strains), Hafnia alvei, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella catarrhalis, Morganella morgannii, Proteus mirabilis, Proteus vulgaris, Proteus penneri, Providencia rettgeri, Providencia stuartii, Providencia alcalifaciens, 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 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-Porphyromonas 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, Prevotella ureolyticus, Prevotella oris, Prevotella buccae, Prevotella denticola, Prevotella levii, Porphyromonas asaccharolyticus, Bifidobacterium spp. Bilophilia wadsworthia, Clostridium perfringens, Clostridium bifermentans, 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, Peptococcus asaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus prevotii, Propionibacterium acnes, Propionibacterium avidium, Propionibacterium granulosum.

Stenotrophomonas maltophilia, Enterococcus faecium, Clostridium difficile and Methicillinum - resistant staphylococcus (MRSA) are steady against drug.

Pharmacokinetics. At in introduction of 250 mg within 30 min. Cmax - 11 mkg/ml, for a dose of 500 mg - 23 mkg/ml, for a dose of 1 g - 49 mkg/ml (there is no absolute pharmacokinetic proportional dependence between the entered dose and Cmax, and also AUC). At increase in a dose from 250 mg to 2000 mg reduction of plasma clearance from 287 to 205 ml/min. is observed. At in bolyusny introduction of 500 mg of a meropenem within 5 min. Cmax - 52 mkg/ml, for a dose of 1 g - 112 mkg/ml. Communication with proteins of plasma – 2%. Well gets into the majority of fabrics and liquids of an organism, including into cerebrospinal liquid of patients with bacterial meningitis, reaching the concentration exceeding demanded for suppression of the majority of 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. In 6 h later in/in introductions of 500 mg the level of a meropenem in plasma decreases to 1 mkg/ml and less. At repeated introduction at an interval of 8 h at patients does not happen to normal function of kidneys of cumulation of a meropenem.

About 70% of the entered dose are removed with urine in not changed look during 12 h then further excretion with urine insignificant. The concentration of a meropenem in urine exceeding 10 mkg/ml is maintained during 5 h after introduction of a dose of 500 mg. At introduction on 500 mg each 8 h or 1000 mg each 12 h were not observed cumulation of a meropenem in plasma and urine. At patients with normal function of kidneys T1/2 makes about 1 h.

Pharmacokinetic parameters of a meropenem at children same, as well as at adults. T½ of a meropenem children up to 2 years have 1,5-2,3 h, the linear pharmacokinetics in the range of doses of 10-40 mg/kg is characteristic.

At patients with a chronic renal failure the clearance of a meropenem correlates with clearance of creatinine therefore reduction of a dose in proportion to decrease in clearance of creatinine without change of intervals between administrations of drug is necessary. At elderly patients decrease in clearance of a meropenem correlates with the decrease in clearance of creatinine connected with age. Diseases of a liver do not exert impact on pharmacokinetics of a meropenem.

Indications to use:

The infectious and inflammatory diseases (monotherapy or in a combination with other antimicrobic medicines (M)) caused by one or several sensitive to meropeny activators: lower respiratory tract infections (including pneumonia, including hospital); infections of abdominal organs (including the complicated appendicitis, peritonitis, a pelviperitonitis); infections of an urinary system (including pyelonephritis, pyelitis); infections of skin and soft tissues (including the ugly face, impetigo for the second time infected a dermatosis); infections of bodies of a small pelvis (including endometritis); bacterial meningitis; empirical treatment (in the form of monotherapy or in a combination with antiviral or antifungal HP) at suspicion of an infection at adult patients with febrile episodes with a neutropenia.

Route of administration and doses:

Enter intravenously bolyusno (in cultivation by sterile water of 5 ml on each 250 mg that provides concentration of solution of 50 mg/ml) within 5 min., or intravenously infusionally, within 15-30 min. (in cultivation by compatible infusional liquid up to 50-200 ml). It is not intended for intramuscular introduction!

The adult at pneumonia, infections of urinary tract, infectious and inflammatory diseases of bodies of a small pelvis, infections of skin and soft tissues - in/in, on 500 mg each 8 h; at hospital pneumonia, peritonitis, suspicion of a bacterial infection at patients with a neutropenia, a septicaemia - in/in, on 1 g each 8 h; at meningitis – in/in on 2 g each 8 h.

At a chronic renal failure and the clearance of creatinine (CC) less than 50 ml/min. adjust a dose depending on KK: at ml/min. KK=26-50 – in/in on 0,5-2 g each 12 h, ml/min. KK=10-25 – in/in on 0,25-1 g each 12 h, KK <10 ml/min. – in/in on 0,25-1 g each 24 h Meropenem is brought at a hemodialysis in this connection if treatment continuation is required, it is recommended that the dose appointed for treatment was entered at the end of the procedure of a hemodialysis to recover effective concentration of a meropenem in plasma.

To children aged from 3 months up to 12 years a single dose for in/in introductions – 10-20 mg/kg each 8 h; to children with body weight more than 50 kg apply dosages to adults; at meningitis or infections against the background of a mucoviscidosis - in/in, 40 mg/kg each 8 h.

At patients of advanced age with normal function of kidneys or KK more than 50 ml/min. are not required to adjust a dose.

Patients with a liver failure have no need for correction of a dose.

At Borinem's cultivation it is necessary to apply standard rules of an asepsis.

Medicine is compatible to the following infusional liquids: 0,9% solution of sodium of chloride, 5% or 10% glucose solution, mix of 5% of solution of glucose from 0,02% bicarbonate sodium solution, mix of 0,9% of solution of sodium of chloride from 5% glucose solution, mix of 5% of solution of glucose from 0,225% chloride sodium solution, mix of 5% of solution of glucose from 0,15% solution of potassium of chloride, 2,5% or 10% Mannitolum solution.

Medicine should not be mixed with the solutions containing other medicines (including heparin).

It is recommended to apply freshly cooked solution of Borinem.

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 in the conditions of continuous monitoring of sensitivity of microbic flora is possible. At the persons with complaints from digestive tract who especially have colitis it is necessary to consider a possibility of development of pseudomembranous colitis (under the influence of the toxin produced by Clostridium difficile against the background of an antibioticotherapia) as which first symptom development of diarrhea against the background of treatment 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.

There is no experience of use of drug for children with a neutropenia, with primary or secondary immunodeficience. Experience of use of a meropenem for children with an abnormal liver function and kidneys is limited.

At pregnancy and a lactation it is necessary to estimate potential advantage and possible risk of use of drug for a fruit, the baby and mother.

Side effects:

From the alimentary system: pains in epigastric area, nausea, vomiting, diarrhea, a lock, anorexia, jaundice, cholestatic hepatitis, a hyperbilirubinemia, increase in activity of "hepatic" transaminases and ShchF, LDG, it is rare - oral cavity candidiasis, a pseudomembranous coloenteritis.

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

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, malignant exudative erythema (Stephens-Johnson's syndrome), Quincke's disease, acute anaphylaxis.

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

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

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

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

Interaction with other medicines:

It is not compatible to heparin.

Gantsiklovir increases risk of development of generalized spasms.

Meropenem reduces concentration of Valproatums in a blood plasma to subtherapeutic level. The HP blocking canalicular secretion (пробенецид, Sulfinpyrazonum), slow down removal and increase concentration in plasma.

Contraindications:

Hypersensitivity, pregnancy, the lactation period, children's age (3 months are younger).

Overdose:

The accidental overdose is possible during treatment, especially at patients with a renal failure.

Symptoms: specific symptoms are absent.

Treatment: carry out symptomatic therapy. Normal there is a bystry elimination of drug kidneys. At patients with renal disturbances the hemodialysis effectively deletes meropeny and its metabolites.

Storage conditions:

In the place protected from light, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to use medicine after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 500 mg in bottles in packaging No. 1, No. 10.