MEROPENABOL

Active material: Meropenem
When ATH: J01DH02
CCF: Antibiotic group of carbapenems
ICD-10 codes (testimony): A03, A39, A40, A41, A46, G00, i33, J15, J15.1, K65.0, L01, L02, L03, L08.0, N10, N11, N70, N71
When CSF: 06.04
Manufacturer: ABOLmed Ltd. (Russia)

Pharmaceutical form, composition and packaging

Powder for solution for i / v administration white or white with a yellowish tint.

Excipients: sodium carbonate.

Glass Bottles (1) – packs cardboard.

Pharmacological action

Antibiotic group of carbapenems for parenteral use. Receptor interaction – specific penicillin binding proteins on the surface of the cytoplasmic membrane, inhibits transpeptidase, inhibits the synthesis of peptidoglycan cell wall (Due to the structural similarity), which ultimately can cause damage and destruction of bacteria. Resistant to renal dehydropeptidase-1, bactericidal effect, easily penetrate cell walls of bacteria, resistant to most β-lactamases, It has a high affinity for penicillin-binding proteins.

Among the known beta-lactam antibiotics has the highest activity against most aerobic and anaerobic Gram-positive and Gram-negative microorganisms.

It is active against gram-positive aerobes: Bacillus spp., Corynebacterium diphtheriae, Enterococcus liquifaciens, Enterococcus avium, Enterococcus faecalis, Listeria monocytogenes, Lactobacillus spp., Nocardia asteroids, Staphylococcus aureus (incl. strains, penicillinase), Staphylococcus spp. (coagulase-negative strains), incl. Staphylococcus saprophyticus, Staphylococcus, Streptococcus pneumoniae (incl. Penicillin-resistant strains), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus, Streptococcus viridans, Streptococcus salivarius, Streptococcus disease, Streptococcus spp. (Group G and F), Rhodococcus equi; Gram-negative aerobic: 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 amalonaticus, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, 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, resistant to penicillin and spectinomycin), Hafnia avenue, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella catarrhalis, Morganella morganii, Proteus is wonderful, Proteus vulgaris, Rettgeri Providence, Providence stuartii, Alcalifaciens Providence, Pasteurella multocida, Pseudomonas shigelloides, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas alcaligenes, Burkholderia cepacia, Pseudomonas fluorescens, Pseudomonas stutzeri, Stenotrophomonas spp., Salmonella spp. (incl. Salmonella typhi), Serratia spp. (incl. Serratia wilting, Liquid sawdust), Shigella sonnei, Shigella flexneri, Shigella dysentery, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio injurious, Yersinia enterocolitica; Anaerobic bacteria: Actinomyces israelii, Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides vulgatus, Bacteroides variable, Bacteroides pneumosintes, Bacteroides coagulans, Bacteroides uniform, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron), Prevotella spp. (incl. Prevotella melaninogenica, Prevotella mouth, Prevotella denticola, Prevotella levii), Porphyromonas spp. (incl. Porphyromonas asaccharolyticus), Bifidobacterium spp., Clostridium perfringens, Clostridium difficile, Clostridium sporogenes, Clostridium corpse, Clostridium sordellii, Clostridium butyricum, Clostridium clostridiiformis, Clostridium Dathan, Eubacter landed, Bacteria aerofaciens, The deadly bacteria, Fusobacterium necrophorum, Mobiluncus curtisii, Mobiluncus woman, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus saccharolyticus, Peptococcus magnus, Peptococcus prevotii, Propionibacterium acne, Propionibacterium avidius, Propionibacterium granulosum.

Pharmacokinetics

Distribution

The on / in the introduction of the drug at a dose of 250 mg C_makh It reached within 30 and m is 11 ug / ml, dose 500 mg C_makh is 23 ug / ml, dose 1 g – 49 ug / ml (absolute pharmacokinetic proportional to the administered dose for C_makh and AUC is not). After increasing the dose to 250 mg 2 Mr. clearance decreases with 287 to 205 ml / min.

The on / bolus dose of the drug 500 mg C_makh It reached within 5 Mines and sostavlet 52 ug / ml, dose 1 g – 112 ug / ml.

Plasma protein binding - 2%. It penetrates 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 (bactericidal concentrations are through 0.5-1.5 hours after the start of infusion). In small amounts into breast milk. Not accumulates.

Metabolism

Subject to an insignificant metabolism in the liver with the formation of a single inactive metabolite.

Deduction

T_1/2 – 1 no, in children under 2 years – 1.5-2.3 no. The dose range 10-40 mg / kg in adults and children there is a linear dependence of the pharmacokinetic parameters. Report the news - 70% in unmodified form for 12 no. The concentration of meropenem in the urine, exceeding 10 ug / ml, maintained for 5 hours after administration at a dose 500 mg. Displayed in hemodialysis.

Pharmacokinetics in special clinical situations

In patients with renal impairment the clearance of meropenem correlates with creatinine clearance.

In elderly patients, a decrease in clearance of meropenem correlates with age-related decrease in creatinine clearance. T_1/2 – 1.5 no.

Testimony

Infectious-inflammatory diseases, caused by susceptible pathogens:

- Bacterial meningitis;

- Infections of the lower respiratory tract (incl. pneumonia, including hospital), infection, caused by Pseudomonas aeruginosa (especially in patients with cystic fibrosis);

- Abdominal infections (peritonitis, pelvioperitonit, complicated appendicitis);

- Pyelonephritis, pyelitis;

- Infections of the skin and soft tissues (incl. mug, impetigo, secondarily infected dermatitis);

- Dysentery;

- Sepsis;

- Bacterial endocarditis;

- Infectious and inflammatory diseases of the pelvic organs (including endometritis);

- Suspected bacterial infection in adults with febrile episodes of neutropenia (empiric treatment).

Dosage regimen

Meropenabol^® administered in the form of I / bolus injection for at least 5 m, or in the form of on / in infusion for 15-30 m.

Dose and duration of therapy should be set depending on the type of, the severity of the infection and condition of the patient.

The recommended daily doses.

Adult

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

At the treatment of nosocomial pneumonia, peritonitis, bacterial infection in patients with neutropenia (febrile neutropenia), and sepsis – in / on 1 g every 8 no.

At treatment of meningitis The recommended dose is 2 g every 8 no.

At chronic renal failure dose is adjusted depending on QC: at CC 26-50 ml / min appoint 0.5-1 g 2 times / day; at CC 10-25 ml / min – by 250-500 mg 2 times / day; at CC less than 10 ml / min – by 500 mg 1 time / day.

Meropenem appear in hemodialysis. If you need long-term 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, effective concentration for restoration of the antibiotic in plasma.

Children

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 use dosage for adults.

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

The maximum dose does not exceed 2 g every 8 no.

Meropenabol^® not recommended for use in children under 3 Months.

No experience with the drug in children with impaired liver and kidney function.

Terms preparing solutions

For in / bolus Meropenabol^® should be diluted with sterile water for injection (10 ml 500 mg of meropenem). This provides concentration of the solution 50 mg / ml.

For in / infusion Meropenabol^® should be diluted with sterile water for injection or compatible liquid for infusion, and then diluted as compatible liquid for infusion (50-200 ml).

Meropenabol^®is compatible with the following infusion fluids:

- 0.9% sodium chloride solution for in / infusion;

- 5% or 10% Dextrose (Glucose) for / in infusion;

- 5% Dextrose (Glucose) for / in infusions 0.02% solution of sodium bicarbonate;

- 0.9% solution of sodium chloride and 5% Dextrose (Glucose) for / in infusion;

- 5% Dextrose (Glucose) from 0.225% sodium chloride solution for in / infusion;

- 5% Dextrose (Glucose) from 0.15% Potassium chloride solution for in / infusion;

- 2.5% and 10% to a solution of mannitol / infusion.

Meropenabol^® It must not be mixed with solutions, containing other drugs.

Side effect

From the digestive system: epigastric pain, nausea, vomiting, diarrhea, cholestatic hepatitis, giperʙiliruʙinemija, increase in liver transaminases and alkaline phosphatase, LDH; rarely - oral candidiasis, pseudomembranous enterocolitis.

Cardio-vascular system: Rituals- or bradycardia, reduction or increase in blood pressure, fainting.

From the urinary system: dizurija, swelling, impairment of renal function (giperkreatininemiя, increasing the concentration of urea in plasma), hematuria.

From the nervous system: headache, paresthesia, insomnia, hypererethism, anxiety, depression, disturbance of consciousness, hallucinations, epileptiform seizures, convulsions.

From the laboratory parameters: eozinofilija, neutropenia, leukopenia, anemia; rarely – agranulocytosis, obratimaya thrombocytopenia, reduction in partial thromboplastin time.

Allergic reactions: itchy skin, skin rash, hives, erythema multiforme exudative, angioedema, anaphylactic shock.

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

Other: positive direct or indirect Coombs test, dyspnoea, vaginal candidiasis.

Contraindications

- Children up to age 3 Months;

- Hypersensitivity to the drug.

FROM caution should be prescribed to patients with allergic reactions to penicillins and cephalosporins history; When specifying a history of diseases of the colon, incl. NYAK; patients with renal and hepatic insufficiency.

Pregnancy and lactation

The safety of the drug during pregnancy has not been determined.

At the time of treatment should stop breastfeeding.

Cautions

Patients, with a history indicate an increased sensitivity to carbapenems, penicillins and other beta-lactam antibiotics, may exhibit hypersensitivity to meropenem.

Treatment of patients with liver disease should be carefully monitored in liver transaminases and bilirubin.

In the treatment of possible development of resistance of pathogens, therefore the long-term treatment is carried out under the permanent control of the spread of drug-resistant strains.

In patients with diseases of the gastrointestinal tract, especially colitis, you must consider the possibility of antibiotic-associated diarrhea and pseudomembranous colitis (toxin, produced by Clostridium difficile, It is one of the main causes of colitis, related antibiotics), which may be the first symptom is the development of diarrhea during treatment.

When monotherapy known or suspected infections of the lower respiratory tract severe, caused by Pseudomonas aeruginosa, It recommends regular definition susceptibility.

Overdose

Accidental overdose is possible during treatment, especially in patients with impaired renal function. Treatment in case of overdose should be symptomatic. Rapid removal of the drug achieved in hemodialysis.

Drug Interactions

Ganciclovir increases the risk of generalized seizures.

Drugs, block tubular secretion, slows down and increase the concentration of meropenem in plasma.

Not compatible with heparin.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dark, dry and away from children at a temperature no higher than 25 ° C. Shelf life – 2 year.

For I / O injection and / infusion is recommended freshly prepared solution Meropenabola^®, however diluted meropenem may retain its activity for 6 h during storage of the solution at a temperature not higher than 25 ° C and 36 h during storage of the solution at a temperature of not higher than 5 ° C. The solution is not to freeze!