Cilastatin sodium. Medicinal reference book geotar

Imipenem + cilastatin INN

International name: Imipenem + Cilastatin

Dosage form: powder for preparing a solution for intramuscular injection, powder for solution for infusion

Pharmachologic effect:

Beta lactam antibiotic a wide range actions. It inhibits the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic. Imipenem is a derivative of thienamycin and belongs to the group of carbapenems. Cilastatin sodium inhibits dehydropeptidase, an enzyme that metabolizes imipenem in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cilastine does not have its own antibacterial activity, does not inhibit bacterial beta-lactamase. Active against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis and Bacteroides fragilis. Resistant to destruction by bacterial beta-lactamase, which makes it effective against many microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp., which are resistant to most beta-lactam antibiotics. The antibacterial spectrum includes almost all clinically significant pathogens.

Pharmacokinetics:

With the / m introduction, the bioavailability of imipenem is 95%, cilastine is 75%. Communication with plasma proteins of imipenem - 20%, cilastine - 40%. Cmax imipenem when administered intravenously at a dose of 250, 500 or 1000 mg over 20 minutes - 14-24, 21-58 and 41-83 mcg / ml, respectively; with the / m administration of 500 or 750 mg - 10 and 12 mcg / ml, respectively. Cmax of cilastin when administered intravenously at a dose of 250, 500 or 1000 mg over 20 minutes - 15-25, 31-49 and 56-80 mcg / ml; with the / m administration of 500 or 750 mg - 24 and 33 mcg / ml, respectively. It is quickly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids and reproductive organs. It is found in the CSF at low concentrations. The volume of distribution in adults is 0.23-0.31 l / kg, in children 2-12 years old - 0.7 l / kg, in newborns - 0.4-0.5 l / kg. Blocking tubular secretion of imipenem by cilastine leads to inhibition of its renal metabolism and accumulation in the urine unchanged. Cilastine is metabolized to an N-acetyl compound. With the / m administration of T1 / 2 imipenem - 2-3 hours. With the / in the introduction of T1 / 2 imipenem and cilastine in adults - 1 hour, in children 2-12 years old - 1-1.2 hours, in newborns T1 / 2 imipenem - 1.7-2.4 hours, cilastin - 3.8-8.4 hours; with impaired renal function T1 / 2 imipenem - 2.9-4 hours, cilastine - 13.3-17.1 hours. Excreted mainly by the kidneys (70-76% within 10 hours) by glomerular filtration (2/3) and active tubular secretion (1/3 ); 1-2% is excreted through bile with feces and 20-25% - extrarenally (mechanism unknown). Quickly and effectively (73-90%) is excreted by hemodialysis (as a result of a 3-hour session of intermittent hemofiltration, 75% of the dose received is removed).

Indications:

Intra-abdominal infections, infections of the lower parts respiratory tract, genitourinary system, bones and joints, skin and soft tissues, pelvic organs, sepsis, bacterial endocarditis, prevention of postoperative infections, mixed infections, nosocomial infections and etc.

Contraindications:

Hypersensitivity (including to carbapenems and other beta-lactam antibiotics), pregnancy (only for "vital" indications), early childhood(up to 3 months); in children - severe kidney failure(serum creatinine greater than 2 mg/dL). For a suspension for intramuscular injection prepared using lidocaine hydrochloride as a solvent - hypersensitivity to local anesthetics of the amide structure (shock, impaired intracardiac conduction). With caution. CNS diseases, lactation, old age.

Dosing regimen:

In/in drip and/m.

Side effects:

From the side nervous system: myoclonus, mental disorders hallucinations, confusion, epileptic seizures, paresthesia. From the urinary system: oliguria, anuria, polyuria, acute renal failure (rarely). From the side digestive system: nausea, vomiting, diarrhea, pseudomembranous enterocolitis, hepatitis (rare). On the part of the hematopoietic organs and the hemostasis system: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, decreased Hb, prolongation of prothrombin time, positive Coombs reaction. Laboratory indicators: increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, increased concentration of urea nitrogen; direct positive Coombs test. Allergic reactions: skin rash, itching, urticaria, multiforme exudative erythema(including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis (rarely), exfoliative dermatitis (rarely), fever, anaphylactic reactions. Local reactions: skin hyperemia, painful infiltrate at the injection site, thrombophlebitis. Others: candidiasis, taste disturbance.

Interaction:

Pharmaceutically incompatible with lactic acid salt, other antibacterial drugs. With simultaneous use with penicillins and cephalosporins, cross-allergy is possible; shows antagonism in relation to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams). Ganciclovir increases the risk of generalized seizures. Drugs that block tubular secretion slightly increase the plasma concentration and T1 / 2 of imipenem (if high concentrations of imipenem are required, it is not recommended to use these drugs at the same time).

Imipenem inhibits bacterial cell wall synthesis. Imipenem has a bactericidal effect against a wide range of pathogenic aerobic and anaerobic gram-negative and gram-positive microorganisms. Imipenem is resistant to cleavage by bacterial beta-lactamases, including cephalosporinase and penicillinase secreted by gram-negative and gram-positive bacteria, which ensures its effectiveness. A feature of imipenem is the preservation of high activity against groups of microorganisms insensitive to other antibiotics. Microorganisms susceptible to imipenem: gram-positive aerobes - Staphylococcus aureus (including penicillinase-producing strains), Enterococcus faecalis, Staphylococcus epidermidis (including penicillinase-producing strains), Streptococcus pneumoniae, Streptococcus agalactiae (group B streptococci), Streptococcus pyogenes, Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus saprophyticus, Green streptococci (Viridans group), Group C and G streptococci; gram-negative aerobes - Citrobacter spp., Enterobacter spp., Acinetobacter spp., Gardnerella vaginalis, Escherichia coli, Klebsiella spp., Haemophilus parainfluenzae, Haemophilus influenzae, Proteus vulgaris, Pseudomonas aeruginosa, Providencia rettgeri, Morganella morganii, Serratia spp. (including Serratia marcescens), Aeromonas hydrophila, Capnocytophaga spp., Alcaligenes spp., Neisseria gonorrhoeae (including penicillinase-producing strains), Haemophilus ducreyi, Providencia stuartii, Pasteurella spp.; gram-positive anaerobes - Eubacterium spp., Clostridium spp., Bifidobacterium spp., Peptostreptococcus spp., Peptococcus spp., Propionibacterium spp.; gram-negative anaerobes - Fusobacterium spp., Bacteroides spp. (including Bacteroides fragilis), Prevotella melaninogenica, Prevotella disiens, VeiIlonella spp., Prevotella bivia. Imipenem is not active against Mycoplasma spp. Chlamydia trachomatis, Enterococcus faecium, some strains of P. cepacia, Xanthomonas (Pseudomonas) maltophilia, methicillin-resistant staphylococci, fungi, viruses.
After intravenous administration of 500 mg of imipenem, the maximum plasma concentration is from 21 to 58 μg / ml and is reached after 20 minutes. The maximum concentration of imipenem decreases to a value of 1 μg / ml and below within 4-6 hours after administration. With intramuscular injection, bioavailability is 95%. The elimination half-life of imipenem is 1 hour. It binds to plasma proteins by 20%. Approximately 70% of intravenously administered imipenem is excreted by the kidneys within 10 hours. The concentration of imipenem in the urine of more than 10 mcg / ml can persist for 8 hours after intravenous administration of the drug. Imipenem is metabolized in the kidneys by the action of renal dehydropeptidase by hydrolysis of the beta-lactam ring. Imipenem is rapidly and widely distributed into most tissues and body fluids. Imipenem after administration was determined in the vitreous body eyeball, intraocular fluid, lung tissue, sputum, pleural fluid, peritoneal fluid, bile, cerebrospinal fluid, endometrium, fallopian tubes, myometrium, bone tissue, interstitial fluid, skin, connective tissue and other tissues and organs. Imipenem is eliminated from the body by hemodialysis.

Indications

Lower respiratory tract infections caused by Staphylococcus aureus (penicillinase-producing strains), Streptococcus pneumoniae, Enterobacter spp., Acinetobacter spp., Escherichia coli, Haemophilus parainfluenzae, Haemophilius influenza, Klebsiella spp., Serratia marcescens; intra-abdominal infections caused by Staphylococcus aureus (penicillinase-producing strains), Enterococcus faecalis, Staphylococcus epidermidis, Enterobacter spp., Citrobacter spp., Escherichia coli, Morganella morganii, Klebsiella spp, Proteus spp., Bifidobacterium spp., Pseudomonas aeruginos, Bacteroides spp. ., Clostridium spp., Peptococcus spp., Peptostreptococcus spp., Eubacterium spp., Propionibacterium spp., Bacteroides fragilis, Fusobacterium spp.; infections urinary tract which are caused by Staphylococcus aureus (penicillinase-producing strains), Enterococcus faecalis, Enterobacter spp., Klebsiella spp, Escherichia coli, Morganella morganii, Providencia rettgeri, Proteus vulgaris, Pseudomonas aeruginosa; gynecological infections caused by Enterococcus faecalis, Staphylococcus epidermidis, Staphylococcus aureus (penicillinase-producing strains), Escherichia coli, Enterobacter spp. spp., Peptococcus spp., Propionibacterium spp., Bacteroides spp., Bacteroides fragilis; bone and joint infections caused by Staphylococcus aureus (penicillinase-producing strains), Enterococcus faecalis, Enterobacter spp., Staphylococcus epidermidis, Pseudomonas aeruginosa; bacterial septicemia caused by Enterococcus faecalis, Streptococcus pneumoniae, Enterobacter spp., Staphylococcus aureus (penicillinase-producing strains), Escherichia coli, Serratia spp., Klebsiella spp, Bacteroides spp., Bacteroides fragilis, Pseudomonas aeruginosa; infective endocarditis, which is caused by Staphylococcus aureus (penicillinase-producing strains); skin and soft tissue infections caused by Enterococcus faecalis, Streptococcus pyogenes, Staphylococcus aureus (penicillinase-producing strains), Acinetobacter spp., Staphylococcus epidermidis, Citrobacter spp., Escherichia coli, Enterobacter spp., Klebsiella spp., Proteus vulgaris, Morganella morganii , Providencia rettgeri, Serratia spp., Pseudomonas aeruginosa, Peptococcus spp., Bacteroides spp., Peptostreptococcus spp., Bacteroides fragilis, Fusobacterium spp.; prevention of postoperative infections in patients with a high risk of intraoperative infection during surgical intervention and in patients at risk with a high probability of developing postoperative infectious complications.

Route of administration of imipenem and dosage

Imipenem is administered intravenously, intramuscularly. The dosage is set individually depending on the indications, tolerability of the drug, condition, age, body weight, kidney function of the patient.
In persons over 65 years of age, given the characteristic age group decreased function of the liver, kidneys, of cardio-vascular system, the presence of comorbidities and concomitant drug treatment, care must be taken when choosing a dose, adhering to the lower limits of the recommended doses. These patients are recommended to be monitored. excretory function kidneys.
Intravenous imipenem is preferred for initial treatment of bacterial sepsis, endocarditis, and other severe or life-threatening infections (including Pseudomonas aeruginosa lower respiratory tract infections), and for significant physiological impairment (eg, shock).
During therapy with imipenem, life-threatening conditions (convulsions, severe anaphylaxis, severe clinical forms pseudomembranous colitis of clostridial etiology), which require special attention and the provision of emergency medical care.
During treatment with imipenem, Pseudomonas aeruginosa can quickly develop resistance to the drug. Therefore, in the process of treating diseases that are caused by Pseudomonas aeruginosa, periodic antibiotic sensitivity tests should be carried out according to the clinical situation.
There is information about partial cross-allergy when using imipenem and other beta-lactam antibiotics (cephalosporins, penicillins). For many antibiotics of the beta-lactam group, the possibility of developing severe reactions (including anaphylaxis) has been reported with their use.
To prevent the development of resistance and maintain the effectiveness of imipenem, the drug should be used only for the treatment of those infections that are caused by susceptible (proven or suspected) microorganisms to imipenem. If there is information about the identified pathogen and its sensitivity to antibiotics, the doctor is guided by it to select the optimal antibiotic, and in the absence of this information, the empirical choice antibacterial agent based on sensitivity data and on the basis of local epidemiological data.
If a patient develops diarrhea during treatment with imipenem, it is first necessary to exclude Clostridium difficile-associated diarrhea, which, under conditions of suppression of the normoflora in the colon, is caused by an aggressive growth of the Clostridium difficile population with the accumulation of toxins A and B produced by the microorganism. Strains that are capable of advanced education toxins, cause the most severe cases that are resistant to any antibacterial treatment and sometimes require colectomy. Perhaps the development of late cases (2 months after completion of treatment) of this complication. If Clostridium difficile-associated diarrhea is suspected or confirmed, imipenem may need to be discontinued with co-administration of treatment to maintain protein parameters, fluid and electrolyte balance, suppress Clostridium difficile infection, and consult a surgeon.
During treatment with imipenem, it is recommended to refrain from performing potentially dangerous activities that require increased attention and speed of psychomotor reactions (including driving vehicles).

Contraindications for use

Hypersensitivity (including to other beta-lactam antibiotics, cephalosporins, penicillins), children under 3 months (for intravenous administration; safety and efficacy have not been established) and up to 12 years (for intramuscular administration; safety and efficacy have not been established), children with impaired renal function (plasma creatinine more than 2 mg / dl), patients with creatinine clearance less than 5 ml / min / 1.73 m2 (for intravenous administration) and less than 20 ml / min / 1.73 m2 (for intramuscular administration), period breastfeeding.

Application restrictions

History of gastrointestinal disease, pseudomembranous colitis, central nervous system disease, patients with creatinine clearance less than 70 ml/min/1.73 m2 (for intravenous administration) and 20 to 70 ml/min/1.73 m2 ( for intramuscular injection), patients on hemodialysis, pregnancy.
Use during pregnancy and lactation
No studies have been conducted on the use of imipenem in pregnant women. Imipenem should only be used in pregnancy when the expected benefit to the mother is greater. possible risk risk to the fetus. During therapy with imipenem, it is necessary to stop breastfeeding (imipenem is excreted with breast milk).

side effects of imipenem

Local reactions: pain at the injection site, phlebitis, thrombophlebitis, vein thickening at the injection site, erythema at the injection site, infection at the injection site.
Digestive system: nausea, vomiting, diarrhea, clostridial pseudomembranous colitis (including after completion of treatment), hepatitis (including fulminant), hemorrhagic colitis, liver failure, gastroenteritis, jaundice, glossitis, abdominal pain, hypertrophy of the papillae of the tongue, pigmentation of the teeth and tongue, sore throat, heartburn, hypersalivation, increased levels of serum transaminases, bilirubin, alkaline phosphatase, increased levels of low density lipoproteins.
Nervous system and sense organs: encephalopathy, confusion, tremor, myoclonus, vertigo, headache, paresthesia, mental disorders, hallucinations, tinnitus, hearing loss, taste perversion.
Respiratory system: shortness of breath, pain in thoracic region spine, chest discomfort, hyperventilation.
Cardiovascular system and blood: palpitations, tachycardia, inhibition of the function of the red germ of the bone marrow, pancytopenia, thrombocytopenia, neutropenia, leukopenia, hemolytic anemia, leukocytosis, eosinophilia, platelets, lymphocytosis, monocytosis, an increase in the number of basophils, agranulocytosis, a decrease in hemoglobin and hematocrit, an increase in prothrombin time, a positive direct Coombs test.
allergic reactions and skin: itching, rash, urticaria, cyanosis, hyperhidrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, exfoliative dermatitis, erythema multiforme, fever, anaphylactic reactions.
Urogenital system: oliguria, polyuria, anuria, proteinuria, leukocyte-, erythrocyte-, cylindruria, increased bilirubin concentration and change in urine color, acute renal failure, increased serum concentration creatinine and urea.
Others: candidiasis, increased plasma concentration of potassium, decreased serum concentration of sodium and chlorine.

Interaction of imipenem with other substances

Cilastatin increases the concentration of unchanged imipenem in the urine and urinary tract by inhibiting its metabolism.
With the combined use of imipenem and ganciclovir, the development of generalized seizures is possible. These drugs should not be administered together, unless the expected benefit of treatment outweighs the possible risk.
The use of probenecid during therapy with imipenem is not recommended, as probenecid increases the plasma concentration and half-life of imipenem.
Imipenem reduces the plasma concentration of valproic acid, which is associated with a risk of increased seizure activity. During co-treatment with imipenem and valproic acid, monitoring of plasma concentrations of valproic acid is recommended.
Imipenem should not be mixed in the same syringe with other antibiotics.

Overdose

No data. In case of an overdose of imipenem, it is recommended to discontinue the drug, prescribe supportive and symptomatic treatment. Imipenem is eliminated by hemodialysis, but the effectiveness of this procedure in case of drug overdose is unknown.

Trade names of drugs with the active substance imipenem

Combined drugs:
Imipenem + Cilastatin: Aquapenem, Grimipenem®, Imipenem and Cilastatin, Imipenem and Cilastatin Jodas, Imipenem and Cilastatin Sodium, Imipenem and Cilastatin Spencer, Imipenem with Cilastatin, Imipenem + Cilastatin, Tienam, Tiepenem®, Cilapenem, Cilaspen.

Model clinical and pharmacological article 1

Pharma action. and Bacteroides fragilis. and Enterobacter spp., (previously (incl. (incl. (incl. (previously (previously Pasteurella) including (incl. (incl. (previously (incl. (incl. (incl. (including strains that form penicillinase), Staphylococcus epidermidis(including strains that form penicillinase), group C, Streptococcus Bacteroides spp.(incl. (previously including (previously (previously (previously (previously (incl. (including Propionibacterium acne); other microorganisms: Some Staphylococcus spp.(methicillin resistant), Streptococcus spp.(Group D), and some strains Pseudomonas cepacia In vitro Pseudomonas aeruginosa.

Pharma action. Broad-spectrum beta-lactam antibiotic. It inhibits the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic. Imipenem is a derivative of thienamycin and belongs to the group of carbapenems. Cilastatin sodium inhibits dehydropeptidase, an enzyme that metabolizes imipenem in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cilastatin does not have its own antibacterial activity, does not inhibit bacterial beta-lactamase. Active towards Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis and Bacteroides fragilis. Resistant to degradation by bacterial beta-lactamase, making it effective against many microorganisms such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp., which are resistant to most beta-lactam antibiotics. The antibacterial spectrum includes almost all clinically significant pathogens. Active against gram-negative aerobic bacteria: Achromobacter spp., Acinetobacter spp.(previously Mima-Herellea), Aeromonas hydrophila, Alcaligenes spp., Bordetella bronchicanis, Bordetella bronchiseptica, Bordetella pertussis, Brucella melitensis, Campylobacter spp., Capnocytophaga spp., Citrobacter spp.(incl. Citrobacter diversus, Citrobacter freundii), Eikenella corrodens, Enterobacter spp.(incl. Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae(including beta-lactamase producing strains), Haemophilus parainfluenzae, Hafnia alvei, Klebsiella spp.(incl. Klebsiella oxytoca, Klebsiella ozaenae, Klebsiella pneumoniae), Moraxella spp., Morganella morganii(previously Proteus morganii, Neisseria gonorrhoeae(including strains that form penicillinase), Neisseria meningitidis, Yersinia spp.(previously Pasteurella) including Yersinia multocida, Yersinia enterocolitica, Yersinia pseudotuberculosis; Plesiomonas shigelloides, Proteus spp.(incl. Proteus mirabilis, Proteus vulgaris), Providencia spp.(incl. Providencia alcalifaciens, Providencia rettgeri(previously Proteus rettgeri), Providencia stuartii), Pseudomonas spp.(incl. Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudomallei, Pseudomonas putida, Pseudomonas stutzeri), Salmonella spp.(incl. Salmonella typhi), Serratia spp.(incl. Serratia marcescens, Serratia proteamaculans), Shigella spp.; Gram-positive aerobic bacteria: Bacillus spp., Enterococcus faecalis, Erysipelothrix rhusiopathiae, Listeria monocytogenes, Nocardia spp., Pediococcus spp., Staphylococcus aureus(including strains that form penicillinase), Staphylococcus epidermidis(including strains that form penicillinase), Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus group C, Streptococcus group G, viridescent streptococci including alpha and gamma hemolytic strains); Gram-negative anaerobic bacteria: Bacteroides spp.(incl. Bacteroides distasonis, Bacteroides fragilis, Prevotella melaninogenica(previously Bacteroides melaninogenicus), Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus), Bilophila wadsworthia, Fusobacterium spp. including (Fusobacterium necrophorum, Fusobacterium nucleatum), Porphyromonas asaccharolytica(previously Bacteroides asaccharolyticus), Prevotella bivia(previously Bacteroides bivius), Prevotella disiens(previously Bacteroides disiens), Prevotella intermedia(previously Bacteroides intermedius), Veillonella spp.; Gram-positive anaerobic bacteria: Actinomyces spp., Bifidobacterium spp., Clostridium spp.(incl. Clostridium perfringens), Eubacter spp., Lactobacillus spp., Microaerophilic streptococcus, Mobiluncus spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp.(including Propionibacterium acne); other microorganisms: Mycobacterium fortuitum, Mycobacterium smegmatis. Some Staphylococcus spp.(methicillin resistant), Streptococcus spp.(Group D), Stenotrophomonas maltophilia, Enterococcus faecium and some strains Pseudomonas cepacia insensitive to imipenem. Effective against many infections caused by bacteria resistant to cephalosporins, aminoglycosides, penicillins. In vitro acts synergistically with aminoglycosides against some strains Pseudomonas aeruginosa.

Pharmacokinetics. With the / m introduction, the bioavailability of imipenem is 95%, cilastatin is 75%. Communication with plasma proteins of imipenem - 20%, cilastatin - 40%. C max imipenem when administered intravenously at a dose of 250, 500 or 1000 mg over 20 minutes - 14-24, 21-58 and 41-83 mcg / ml, respectively; with the / m administration of 500 or 750 mg - 10 and 12 mcg / ml, respectively. C max cilastatin when administered intravenously at a dose of 250, 500 or 1000 mg over 20 minutes - 15-25, 31-49 and 56-80 mcg / ml; with the / m administration of 500 or 750 mg - 24 and 33 mcg / ml, respectively. It is quickly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids and reproductive organs. It is found in the CSF at low concentrations. The volume of distribution in adults is 0.23-0.31 l / kg, in children 2-12 years old - 0.7 l / kg, in newborns - 0.4-0.5 l / kg. Blocking tubular secretion of imipenem by cilastatin leads to inhibition of its renal metabolism and accumulation in the urine unchanged. Cilastatin is metabolized to an N-acetyl compound. With intramuscular injection T 1/2 of imipenem - 2-3 hours. With intravenous administration of T 1/2 of imipenem and cilastatin in adults - 1 hour, in children 2-12 years old - 1-1.2 hours, in newborns T 1/2 imipenem - 1.7-2.4 hours, cilastatin - 3.8-8.4 hours; in case of impaired renal function T 1/2 of imipenem - 2.9-4 hours, cilastatin - 13.3-17.1 hours. It is excreted mainly by the kidneys (70-76% within 10 hours) by glomerular filtration (2/3) and active tubular secretion (1/3); 1-2% is excreted through bile with feces and 20-25% - extrarenally (mechanism unknown). Quickly and effectively (73-90%) is excreted by hemodialysis (as a result of a 3-hour session of intermittent hemofiltration, 75% of the dose received is removed).

Indications. Intra-abdominal infections, infections of the lower respiratory tract, genitourinary system, bones and joints, skin and soft tissues, pelvic organs, sepsis, bacterial endocarditis, prevention of postoperative infections, mixed infections, nosocomial infections, etc.

Contraindications. Hypersensitivity (including to carbapenems and other beta-lactam antibiotics), pregnancy (only for "vital" indications), early childhood (up to 3 months); in children - severe renal failure (serum creatinine concentration more than 2 mg / dl). For a suspension for intramuscular injection prepared using lidocaine hydrochloride as a solvent - hypersensitivity to local anesthetics of the amide structure (shock, impaired intracardiac conduction).

Carefully. CNS diseases, lactation period, old age.

Dosing. In / in drip and in / m. The doses given below are calculated for a body weight of 70 kg or more and a CC of 70 ml / min / 1.73 sq.m or more. For patients with CC less than 70 ml / min / 1.73 sq.m and / or less body weight, the dose should be proportionally reduced. It is preferable to use the intravenous route of administration at the initial stages of therapy for bacterial sepsis, endocarditis, and other severe and life-threatening infections, incl. lower respiratory tract infections caused by Pseudomonas aeruginosa, and in severe complications.

To prepare an infusion solution, 100 ml of a solvent (0.9% NaCl solution, 5% water solution dextrose, 10% aqueous dextrose solution, 5% dextrose solution and 0.9% NaCl, etc.). The concentration of imipenem in the resulting solution is 5 mg/ml.

Medium therapeutic dose for adults with a / in the introduction - 1-2 g / day, divided into 3-4 injections; maximum daily dose— 4 g or 50 mg/kg, whichever is the lower dose. Patients with mild infection - 250 mg 4 times a day, medium degree- 500 mg 3 times a day or 1 g 2 times a day, severe - 500 mg 4 times a day, with a life-threatening infection of the patient - 1 g 3-4 times a day. Each 250-500 mg is administered intravenously over 20-30 minutes, and every 1 g over 40-60 minutes.

For the prevention of postoperative infections - 1 g during induction anesthesia and 1 g - after 3 hours. In case of surgical intervention with a high degree the risk of infection (colon and rectum surgery), an additional 500 mg is administered 8 and 16 hours after general anesthesia.

Maximum daily doses for intravenous administration in patients with renal insufficiency, depending on the severity of the infection and CC values ​​(ml / min / 1.73 sq.m):

with mild infection and CC 41-70 ml / min - 250 mg every 8 hours, CC 21-40 ml / min - 250 mg every 12 hours, CC 6-20 ml / min - 250 mg every 12 hours;

with infection moderate and CC 41-70 ml / min - 250 mg every 6 hours, CC 21-40 ml / min - 250 mg every 8 hours, CC 6-20 ml / min - 250 mg every 12 hours;

in severe cases (highly sensitive strains) and CC 41-70 ml / min - 500 mg every 8 hours, CC 21-40 ml / min - 250 mg every 6 hours, CC 6-20 ml / min - 250 mg every other 12 noon; in severe cases (moderately sensitive strains, incl. Pseudomonas aeruginosa) and CC 41-70 ml / min - 500 mg every 6 hours, CC 21-40 ml / min - 500 mg every 8 hours, CC 6-20 ml / min - 500 mg every 12 hours; in severe life-threatening infections and CC 41-70 ml / min - 750 mg every 8 hours, CC 21-40 ml / min - 500 mg every 6 hours, CC 6-20 ml / min - 500 mg after 12 hours

Patients with CC less than 5 ml / min are prescribed only if hemodialysis is performed every 48 hours, followed by administration after 12 hours (from the moment the procedure is completed).

For the prevention of postoperative infections in adults - 1 g during induction anesthesia and again after 3 hours; in surgical interventions with a high degree of risk (on the colon and rectum) - an additional 500 mg is administered 8 and 16 hours after the start of general anesthesia. Currently, there are no sufficient data on the dosing regimen for preoperative prophylaxis of patients with CC less than 70 ml / min / 1.73 sq.m.

Children weighing 40 kg or more - the same doses as adults; with a body weight of less than 40 kg - 15 mg / kg 4 times a day; the maximum daily dose is 2 g.

IM administration can be used as an alternative to IM formulation for the treatment of infections where IM administration is preferable. Depending on the severity of the infection, the sensitivity of pathogenic microorganisms and the patient's condition, 500-750 mg is administered every 12 hours. The total daily dose is not more than 1500 mg. If there is a need for large doses of the drug, it is necessary to use intravenous administration.

In / m administration in patients with CC less than 20 ml / min / 1.73 sq.m, as well as in children, has not been studied.

For the treatment of urethritis and cervicitis caused by Neisseria gonorrhoeae, enter 500 mg once, in / m. The powder is mixed with 2 ml of 1% lidocaine hydrochloride solution (without epinephrine), water for injection or 0.9% NaCl solution until a homogeneous suspension (white or slightly yellow) is formed.

Side effect. From the nervous system: myoclonus, mental disorders, hallucinations, confusion, epileptic seizures, paresthesia.

From the urinary system: oliguria, anuria, polyuria, acute renal failure (rarely).

From the digestive system: nausea, vomiting, diarrhea, pseudomembranous enterocolitis, hepatitis (rarely).

On the part of the hematopoietic organs and the hemostasis system: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, decreased Hb, prolongation of prothrombin time, positive Coombs reaction.

Laboratory indicators: increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, increased concentration of urea nitrogen; direct positive Coombs test.

Allergic reactions: skin rash, itching, urticaria, erythema multiforme exudative (including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis (rarely), exfoliative dermatitis (rarely), fever, anaphylactic reactions.

Local reactions: skin hyperemia, painful infiltrate at the injection site, thrombophlebitis.

Others: candidiasis, taste disturbance.

Interaction. Pharmaceutically incompatible with lactic acid salt, other antibacterial drugs.

With simultaneous use with penicillins and cephalosporins, cross-allergy is possible; shows antagonism in relation to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

Ganciclovir increases the risk of generalized seizures.

Drugs that block tubular secretion slightly increase the plasma concentration and half-life of imipenem (if high concentrations of imipenem are required, it is not recommended to use these drugs at the same time).

Colors urine reddish.

Dosage form for intramuscular injection should not be used for intravenous injection and vice versa.

Before starting therapy, a thorough history should be taken for previous allergic reactions to beta-lactam antibiotics. Individuals with a history of gastrointestinal disease (especially colitis) have an increased risk of developing pseudomembranous enterocolitis.

Therapy with antiepileptic drugs in patients with a history of brain injury or seizures should continue for the entire period of drug treatment (to avoid side effects from the central nervous system).

It should be borne in mind that elderly patients are likely to have age-related renal dysfunction, which may require dose reduction.

State register of medicines. Official publication: in 2 volumes - M .: Medical Council, 2009. - V.2, part 1 - 568 p.; part 2 - 560 p.

Antibiotic of the carbapenem group

Active ingredients

Cilastatin (cilastatin)
- imipenem (as monohydrate) (imipenem)

Release form, composition and packaging

Powder for solution for infusion white or white with a yellowish tint.

bottles (1) - packs of cardboard.
bottles (10) - cardboard boxes.
bottles (50) - cardboard boxes (for hospitals).
bottles (1-50) - cardboard boxes (for hospitals).

pharmachologic effect

Imipenem is a broad-spectrum beta-lactam antibiotic, is a derivative of thienamycin and belongs to the group of carbapenems. Suppresses the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative. aerobic and anaerobic microorganisms. Cilastatin sodium inhibits dehydropeptidase, an enzyme that metabolizes imipenem in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cilastatin does not have its own antibacterial activity, does not inhibit bacterial beta-lactamase.

Imipenem + cilastatin is resistant to destruction by bacterial beta-lactamases, which makes it effective against most beta-lactamase producing microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacler spp. resistant to penicillins and cephalosporins.

Imipenem + cilastatin has a bactericidal effect in vivo on the following microorganisms:

Enterococcus faecalis, Staphylococcus aureus (including strains that form penicillinase), Slaphylococcus epidermidis (including strains that form penicillinase). Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes;

Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia spp., including Serratia marcescens;

Gram-positive anaerobic bacteria: Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp.

Gram-negative anaerobic bacteria: Bacleroides spp., including Bacteroides fragilis, Fusobacterium spp.

Imipenem is bactericidal in vitro against the following microorganisms:

Gram-positive aerobic bacteria: Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus saprophyticus, Streptococcus groups C, G and viridans group;

Gram-negative aerobic bacteria: Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducreyi, Neisseria gonorrhoeae, including penicillinase-producing strains, Pasteurella spp., Providencia stuartii; gram-negative anaerobic bacteria: Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Veillonella spp.

Insensitive: Enterococcus faecium, methicillin-resistant Staphylococcus spp., Xanthomonas maltophilia, Pseudomonas cepacia.

In vitro, it acts synergistically with aminoglycosides against certain strains of Pseudomonas aeruginosa.

Pharmacokinetics

The maximum concentration (C max) of imipenem when administered intravenously (in / in) at a dose of 250 mg, 500 mg, 1000 mg over 20 minutes - 14-24 μg / ml, 21-58 μg / ml, 41-83 μg / ml respectively. C max cilastatin when administered intravenously at a dose of 250 mg, 500 mg, 1000 mg over 20 minutes - 15-25 μg / ml, 31-49 μg / ml, 56-80 μg / ml, respectively. 20% of the administered dose of imipenem and 40% of cilastatin are reversibly bound to blood proteins.

Imipenem is well and rapidly distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids, reproductive organs. Found at low concentrations in cerebrospinal fluid(CSJ). The volume of distribution in adults is 0.23-0.31 l / kg, in children 2-12 years old - 0.7 l / kg, in newborns - 0.4-0.5 l / kg. Both components of the drug are excreted mainly by the kidneys (70-76% within 10 hours) by glomerular filtration (2/3) and active tubular secretion (1/3): 1-2% is excreted through the intestines and 20-25% - extrarenal ( mechanism unknown).

With intravenous administration, the half-life (T 1/2) of imipenem and cilastatin in adults is 1 hour, in children 2-12 years old - 1-1.2 hours, in newborns T 1/2 of imipenem - 1.7-2.4 hours , cilastatin -3.8-8.4 h; in case of impaired renal function T 1/2 imipenem - 2.9-4 hours. Cilastatin - 13.3-17.1 hours.

Imipenem and cilastatin are quickly and effectively (73-90%) excreted by hemodialysis (as a result of a 3-hour session of intermittent hemofiltration, 75% of the administered dose is removed).

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

• lower respiratory tract infections;
• urinary tract infections;
• intra-abdominal infections;
• gynecological infections;
• bacterial septicemia;
• bone and joint infections;
• skin and soft tissue infections;
• bacterial endocarditis.

Prevention of postoperative infectious complications.

Contraindications

• hypersensitivity to one of the components of the drug, as well as to other carbapenems, beta-lactam antibiotics, penicillins and cephalosporins;
• chronic renal failure with CC less than 5 ml / min / 1.73 m 2 without hemodialysis;
• early childhood (up to 3 months);
• in children - severe renal failure (serum creatinine concentration more than 2 mg / dl).

Carefully

Diseases of the central nervous system (CNS), pseudomembranous colitis, patients with a history of gastrointestinal diseases, with CC less than 70 ml / min / 1.73 m 2, patients on hemodialysis, anticonvulsant therapy (decrease in the effectiveness of therapy), old age.

Dosage

Intravenous drip.

Dosage form for intravenous administration should not be administered intramuscularly.

The average therapeutic dose for adults with a body weight greater than or equal to 70 kg and normal kidney function (CC 70 ml / min / 1.73 m 2 or more) - 1-2 g / day (calculated as imipenem), divided into 3-4 injections.

The maximum daily dose is 4 g or 50 mg/kg, whichever is the lower dose.

• at mild infections and uncomplicated urinary tract infections- 250 mg 4 times a day (total daily dose 1 g);
• at moderate course- 500 mg 3 times a day or 1000 mg 2 times a day (total daily dose 1.5-2 g);
• at severe and complicated urinary tract infections- 500 mg 4 times a day (total daily dose 2 g);
• at life-threatening infection- 1000 mg 3-4 times a day (total daily dose 3-4 g).

For prevention of postoperative infections- 1000 mg during induction anesthesia and 1000 mg after 3 hours. In the case of surgery with a high risk of infection (colon and rectum surgery), an additional 500 mg is administered 8 hours and 16 hours after general anesthesia.

For patients with QC less than 70 ml / min / 1.73 m 2 and/or weighing less than 70 kg the dose should be proportionally reduced (calculation of doses according to imipenem):

Maximum daily dose 1.0 g

Body weight, kg
	≥71	41-70	21-40	6-20
≥70	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
60-69	250 mg every 8 hours	125 mg every 6 hours	250 mg every 12 hours	125 mg every 12 hours
50-59	125 mg every 6 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
40-49	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours
30-39	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours

Maximum daily dose 1.5 g

body weight kg	Creatinine clearance, ml / min / 1.73 m 2
	≥71	41-70	21-40	6-20
≥70	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
60-69	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours
50-59	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
40-49	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
30-39	125 mg every 6 hours	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours

Maximum daily dose 2.0 g

Body weight, kg	Creatinine clearance, ml / min / 1.73 m 2
	≥71	41-70	21-40	6-20
≥70	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
60-69	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
50-59	250 mg every 6 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
40-49	250 mg every 6 hours	250 mg every X hours	250 mg every 12 hours	250 mg every 12 hours
30-39	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours

Maximum daily dose 3.0 g

Body weight, kg	Creatinine clearance. ml / min / 1.73 m 2
	≥71	41-70	21-40	6-20
≥70	1000 mg every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
60-69	750 mg every 8 hours	500 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
50-59	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
40-49	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
30-39	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours

Maximum daily dose 4.0 g

Body weight, kg	Creatinine clearance, ml / min / 1.73 m 2
	≥71	41-70	21-40	6-20
≥70	1000 mg every 6 hours	750 mg every 8 hours	500 mg every 6 hours	500 mg every 12 hours
60-69	1000 mg every 8 hours	750 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
50-59	750 mg every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
40-49	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
30-39	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours

In patients with QC less than 5 ml / min / 1.73 m 2 the drug is administered only if hemodialysis is carried out no later than 48 hours later.

In patients with QC less than 5 ml / min / 1.73 m 2 who are on hemodialysis, the drug should be administered at doses recommended for patients with CC 6-20 ml / min / 1.73 m 2 immediately after a hemodialysis session and at 12-hour intervals from the moment the procedure is completed. Patients on hemodialysis, especially those with CNS disease, should be closely monitored. The use of the drug in patients on hemodialysis is recommended only in cases where the benefit of treatment outweighs the potential risk of seizures. Currently, there are insufficient data to recommend the use of the drug in patients on peritoneal dialysis.

At children from 3 months of age, weighing up to 40 kg, a single dose is 15 mg / kg, which is administered every 6 hours. The maximum daily dose is 2 g.

Children weighing 40 kg or more prescribe the same doses as adults (see tables).

Preparation of solution for infusion and administration

Add 10 ml or 20 ml of a suitable solvent to the vial with the preparation. Shake the bottle well to obtain a homogeneous suspension.

The resulting suspension must not be used for administration!

The resulting suspension is transferred into a vial with the rest of the solvent (80-90 ml). The total volume of the solution is 100 ml. For complete transfer of the drug (residue of the drug on the walls of the vial), add 20 ml of the previously obtained solution to the vial, shake well, then combine both solutions. Stir the resulting solution thoroughly until it becomes clear. Only then is the solution ready for use. The total volume of the solution is 100 ml. Differences in the color of the solution from colorless to yellow do not affect the activity of the drug.

Enter intravenously drip.

The duration of the infusion depends on the selected dose: 250-500 mg administered over 20-30 minutes; over 500 mg - within 40-60 minutes. Patients who experience nausea during the infusion should reduce the rate of administration of the drug.

Ready solutions for infusion (imipenem concentration 5 mg/ml) can be stored for 4 hours at room temperature or for 24 hours in the refrigerator.

The table presents data on the terms of stability of drug solutions prepared on the basis of a number of infusion solutions.

Side effects

From the side of the central nervous system: dizziness, drowsiness, myoclonus, mental disorders, hallucinations, confusion, convulsions, paresthesia, encephalopathy, tremor, headache, vertigo.

From the sense organs: hearing loss, ringing in the ears, taste disturbance.

From the urinary system: oliguria, anuria, polyuria, acute renal failure, changes in urine color.

From the digestive system: nausea, vomiting, diarrhea, pseudomembranous colitis, hemorrhagic colitis, hepatitis (including fulminant), liver failure, jaundice, gastroenteritis, abdominal pain, glossitis, hypertrophy of the papillae of the tongue, staining of the teeth or tongue, sore throat, hypersalivation, heartburn.

From the side of the respiratory system: chest discomfort, shortness of breath, hyperventilation.

From the side of the hematopoietic organs: eosinophilia. leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, leukocytosis, basophilia, pancytopenia, depression of bone marrow hematopoiesis, hemolytic anemia.

Laboratory indicators: increased activity of "liver" transaminases and alkaline phosphatase, lactate dehydrogenase, hypercreatininemia, hyperbilirubinemia, increased concentration of urea nitrogen; false positive direct Coombs test; decrease in hemoglobin and hematocrit, prolongation of prothrombin time; increased concentration of low density lipoproteins; hyponatremia, hyperkalemia, hypochloremia; the appearance of protein, erythrocytes, leukocytes, cylinders, an increase in the concentration of bilirubin in the urine.

Allergic reactions: skin rash, itching, urticaria, erythema multiforme, Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis, exfoliative dermatitis, fever, anaphylactic reactions.

From the side of the cardiovascular system: decline blood pressure, palpitations, tachycardia.

Local reactions: skin hyperemia, painful infiltrate at the injection site, phlebitis/thrombophlebitis.

Others: candidiasis, vaginal itching, cyanosis, hyperhidrosis, polyarthralgia, asthenia, burning behind the sternum, pain in the thoracic spine.

Overdose

drug interaction

Pharmaceutically incompatible with lactic acid salt, solutions of other antibiotics.

With simultaneous use with penicillins and cephalosporins, cross-allergy is possible; shows antagonism to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).

With simultaneous use with increases the risk of developing generalized seizures. These drugs should not be used simultaneously, unless the potential benefits outweigh the possible risks.

Drugs that block tubular secretion slightly increase the plasma concentration and half-life of imipenem (if high concentrations of imipenem are required, use these medicines not recommended at the same time).

When using the drug, the serum concentration of valproic acid decreases, which leads to a decrease in the effectiveness of anticonvulsant therapy, therefore, during the period of treatment, it is recommended to monitor the serum concentration of valproic acid.

special instructions

Strict adherence to the recommended dosage and regimen is strongly required, especially in patients predisposed to convulsive activity. Therapy with anticonvulsants in patients with a history of epilepsy should continue for the entire period of treatment with the drug. If localized tremors, myoclonus, or seizures are observed, patients should undergo a neurological examination with anticonvulsant therapy. The dosage of the drug in this case should be reviewed to determine whether it should be reduced or the drug should be discontinued.

The dosage form contains 37.56 mg (1.63 meq) of sodium.

Before starting therapy, a thorough history should be taken for previous allergic reactions to beta-lactam antibiotics. With the development allergic reaction the drug should be discontinued immediately.

Individuals with a history of gastrointestinal disease (especially colitis) have an increased risk of developing pseudomembranous colitis.

When using the drug, both against the background of the introduction, and after 2-3 weeks. after discontinuation of treatment, diarrhea caused by Clostridium difficile (pseudomembranous colitis) may develop. In mild cases, it is sufficient to cancel treatment and use ion-exchange resins (colestyramine, colestipol), in severe cases, compensation for the loss of fluid, electrolytes and protein, the appointment of vancomycin and metronidazole are indicated. Do not use drugs that inhibit intestinal motility.

As with other beta-lactam antibiotics, Pseudomonas aeruginosa can develop resistance to the drug fairly quickly during treatment. Therefore, during the treatment of infections caused by Pseudomonas aeruginosa, it is recommended to conduct periodic antibiotic sensitivity tests according to the clinical situation.

Elderly patients are likely to have age-related renal dysfunction, which may require dose reduction.

Colors urine reddish.

Influence on the ability to drive vehicles and work with mechanisms

Care should be taken when driving a car and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Pregnancy and lactation

Use during pregnancy is permissible only if possible benefit from treatment to the mother outweighs the potential risk to the fetus.

Imipenem and cilastatin pass in small amounts into breast milk, so the issue of stopping breastfeeding during treatment with the drug should be considered.

Dropped by prescription.

Terms and conditions of storage

In a place protected from light at a temperature not exceeding 25 ° C. Keep out of the reach of children. Best before date. 2 years.

Dosage form:  powder for solution for infusion Compound:

For 1 vial/bottle:

Sterile mixture containing:

active substances: imipenem monohydrate - 530.0 mg (in terms of imipenem - 500.0 mg), cilastatin sodium - 532.0 mg (in terms of cilastatin - 500.0 mg);

excipient: sodium bicarbonate - 20.0 mg.

Description: B white or white powder with a yellowish tint. Pharmacotherapeutic group:Antibiotic carbapenem + dehydropeptidase inhibitor ATX:  

J.01.D.H.51 Imipenem and dehydropeptidase inhibitor

Pharmacodynamics:

The drug consists of two components:

1) imipenem, a broad-spectrum beta-lactam antibiotic, a derivative of thienampcin, belonging to the group of carbaienems;

2) cilastatin sodium - an enzyme-inhibitor of imipenem metabolism in the kidneys and significantly increasing the concentration of unchanged imipenem in the urinary tract.

Imipenem inhibits the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative aerobic and anaerobic microorganisms.

Cilastine does not have its own antibacterial activity, does not inhibit bacterial beta-lactamase.

Imipenem is resistant to degradation by bacterial beta-lactamase, making it effective against many microorganisms such as Pseudomonasaeruginosa, Serratiaspp. and Enterobacterspp ., which are resistant to most beta-lactam antibiotics.

The antibacterial spectrum includes almost all clinically significant pathogens.

Active against the following microorganisms in vitro, and also in vivo:

Gram-negative aerobic bacteria : A cinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia spp., including Serratia marcescens;

Gram-positive aerobic bacteria : Enterococcusfaecalis, Staphylococcus aureus Staphylococcus epidermidis(including strains that form penicillinase), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes;

Gram-negative anaerobic bacteria :Bacteroides spp., including Baeteroides fragilis, Fusobacterium spp;

Gram-positive anaerobic bacteria : Bifidobacterium spp., Clostridium spp., Eubaeterium spp., Peptocoecus spp., Peplostreptococcus spp., Propionibacterium spp.

Imipenem is bactericidal in vitro against the following microorganisms ( clinical efficacy not established)

Gram-positive aerobes : Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus saprophyticus, Streptococcus groups C, G and the viridans group;

Gram-negative aerobes : Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducreyi, Neisseria gonorrhoeae, including strains that form penicillinase, Pasteurella spp., Providencia stuartii;

Gram-negative anaerobes : Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Veillonella spp.;

insensitive : Enterococcus faecium, methicillin-resistant Staphylococcus spp., Xanthomonas maltophilia, Burkholderia cepacia.

Invitro acts synergistically with aminoglycosides against some strains Pseudomonasaeruginosa .

Pharmacokinetics:

After the on / in the introduction of the drug solution, the time to reach the maximum concentration (TC m ah) in plasma is 20 minutes for both components. At the same time, the maximum concentration (C m ax) reaches values ​​from 21 to 58 μg ml for imipenem and from 21 to 55 μg / ml for cilastatin. After the administration of the drug within 4-6 hours, C m ax of imipenem decreases to a value of 1 μg / ml and below.

The elimination half-life for each of the components is 1 hour.

Plasma protein binding is 20% for imipenem and 40% for cilastatin.

Approximately 7% of intravenous imipenem is excreted by the kidneys within 10 hours. The concentration of imipenem in the urine over 10 mcg / ml can persist for 8 hours after the on / in the introduction of the drug. About 70-80% of cilastatin is excreted by the kidneys within 10 hours after administration of the drug.

With intravenous administration of the drug every 6 hours in patients with normal renal function, no accumulation of imipenem / cilastatin in plasma or urine was observed.

After injecting the drug at a dose of 1 g, the following average concentrations of imipenem in tissues and media of the human body were determined:

Tissue or medium	Imipenem concentration mcg/ml or mcg/g	Measurement time (h)
vitreous body eyeball
intraocular fluid
lung tissue
Pleural fluid
peritoneal fluid
Liquor (no inflammation)
Liquor (for inflammation)
The secret of the prostate
prostate tissue
Fallopian tubes
endometrium
Myometrium
Bone
interstitial fluid
Connective tissue

Indications:

The drug is used to treat severe infections caused by microorganisms sensitive to it, as well as for empirical therapy infectious process even before the determination of its bacterial pathogens.

Intra-abdominal infections caused by Enterococcusfaccalis, Staphylococcusaureus Staphylococcus epidermidis Citrobacter spp. Enterobacter spp. Escherichia coli Klebsiella spp. Morganella morganii Proteus spp. Pseudomonas aeruginosa Bifidobacterium spp. Clostridium spp. Eubacterium spp. Peptococcus spp. Peptostreptococcuspi bpp. spp., Bacteroides spp., including

Lower respiratory tract infections caused by Streptococcus pneumoniae, Staphylococcus aureus (penicillinase-producing strains), Acinetobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Serratia marcescens.

Urinary tract infections (complicated and uncomplicated) caused by Enterococcus faecalis, Staphylococcus aureus(penicillinase-producing strains), E nterobacterspp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri. Pseudomonas aeruginosa.

Skin and soft tissue infections caused by Streptococcus pyogenes, Enterococcus faecalis, Staphylococcus aureus(penicillinase-producing strains), Staphylococcus epidermidis, Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa; Serratia spp., Peptococcus spp., Peptostreptococcus spp., Bacteroides spp., including B. fragilis, Fusobacterium spp.

Bone and joint infections caused by Enterococcus faecalis, Staphylococcus aureus(penicillinase-producing strains), Staphylococcus epidermidis, Enterobacter spp., Pseudomonas aeruginosa.

Bacterial septicemia caused by Streptococcus pneumoniae, Enterococcus faecalis, Staphylococcus aureus(penicillinase-producing strains), Enterobacter spp., Escherichia coli. Klebsiella spp., Pseudomonas aeruginosa, Serratia spp., Bacteroides spp., including Bacteroides fragilis.

Infective endocarditis. caused Staphylococcus aureus (penicillinase-producing strains).

Gynecological infections caused byEnterococcus faecalis, Staphylococcus aureus(penicillinase-producing strains).Staphylococcus epidermidis, Streptococcus agalactiae (Streptococcus spp. group B) Enterobacter spp ., Escherichia coli , Gardnerella vaginalis , Klebsiella spp ., Proteus spp ., Bifidobacterium spp ., Peptococcus spp ., Peptostreptococcus spp ., Propionibacterium spp ., Bacteroides spp ., including B. fragilis.

Prevention postoperative complications in patients at risk with a high probability of developing postoperative infectious complications, as well as in patients with a high risk of intraoperative infection during surgery.

Contraindications:

Hypersensitivity to any of the components of the drug; hypersensitivity to other carbapenems.

Severe hypersensitivity reactions (eg, anaphylactic reactions, severe skin reactions) to any other beta-lactam antibiotics (eg, penicillins or cephalosporins).

Children up to 3 months.

Children with impaired renal function (serum creatinine greater than 2 mg/dL).

Patients with creatinine clearance (CC) less than 5 ml / min / 1.73 m 2 (unless hemodialysis is performed no later than 48 hours after the infusion of the drug).

Carefully:

Diseases of the central nervous system, with CC less than 70 ml / min 1.73 m 2, patients on hemodialysis, patients with diseases of the gastrointestinal tract in history, pseudomembranous colitis.

Pregnancy and lactation:

No studies have been conducted in pregnant women. The drug should be used during pregnancy only if the benefit of treatment justifies the potential risk to the fetus.

Imipenem is found in breast milk. If the use of the drug is considered necessary, then breastfeeding should be discontinued.

Dosage and administration:

THE DOSAGE FORM FOR INTRAVENOUS USE SHOULD NOT BE INTRODUCED IMMEDIATELY.

The calculation of the total daily dose of the drug should be based on the severity of the infection and distributed over several applications in equal doses, taking into account the degree of sensitivity of one or more pathogens, kidney function and body weight.

Dosing regimen for adult patients with normal renal function

The doses given in Table 1 are calculated for patients with normal renal function (creatinine clearance greater than 70 ml / min / 1.73 m 2) and body weight ≥70 kg.

In patients with creatinine clearance ≤70 ml / min / 1.73 m 2 (see Table 2) and / or body weight less than 70 kg (see Table 3), a dose reduction is necessary. It is especially important to reduce the dose depending on body weight in those patients whose weight is significantly less than 70 kg, and or there is moderate or severe renal insufficiency.

The average therapeutic daily dose is 1-2 g of imipenem divided into 3-4 applications (see Table 1). For the treatment of moderate infections, the drug can also be used at a dose of 1 g twice a day.

In the case of infections caused by less sensitive microorganisms, the daily dose of the drug for intravenous infusion may be increased to a maximum of 4 g (imipenem) per day or 50 mg/kg per day, whichever is the lower dose.

Each dose of the drug for intravenous infusion, less than or equal to 500 mg should be administered intravenously over 20-30 minutes. Each dose over 500 mg should be administered intravenously over 40-60 minutes.

Patients who experience nausea during the infusion should slow down the rate of administration of the drug.

Table 1 Dosing regimen for intravenous infusion in adult patients with normal renal function and body weight ≥70 kg*

Infection severity	Dose imipenem, mg	Break between infusions	Total daily dose
Severe (susceptible pathogens)
Severe and or life threatening
Severe and or life-threatening caused by less sensitive organisms (primarily some strains R. aeruginosa)

* In patients weighing less than 70 kg, a further proportional reduction in administered doses is necessary.

Due to the high antimicrobial activity of the drug, it is recommended that its total daily dose not exceed 50 mg kg or 4 g (imipenem) per day, whichever is the lower dose.

Although patients with cystic fibrosis with normal renal function were treated with the drug at a dose of up to 90 mg/kg per day, divided into several applications, the total dose did not exceed 4 g (imipenem) per day.

The drug has been successfully used as monotherapy in immunocompromised cancer patients with confirmed or suspected infections, such as sepsis.

Dosing schedule for adult patients with impaired renal function

To adjust the dose of the drug in the treatment of adult patients with impaired renal function, it is necessary:

• Based on the characteristics of the infection, select the total daily dose of the drug from Table 1.
• From Table 2, select the appropriate reduced dose of the drug, based on the daily dose (Table 1) and the patient's creatinine clearance. (For timing of infusion, see Dosing Schedule for Adults with Normal Renal Function).
• From Table 3, select in the left column the body weight closest to the patient's body weight (kg).

Table 2. Dosing regimen of the drug for intravenous infusion in adult patients with impaired function kidneys and body weight ≥70 kg*

General daily dose of imipenem, from Table 1
	41-70	21-40	6-20
1.0 g per day	250 mg every 8 hours	250 mg every 12 hours	250 mg every 8 hours
1.5 g per day	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
2.0 g per day	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
3.0 g per day	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
4.0 g per day	750 mg every 8 hours	500 mg every 6 hours	500 mg every 12 hours

* In patients weighing less than 70 kg, a further proportional reduction in administered doses is necessary.

Table 3. Dosing regimen for the drug for intravenous infusion in adult patients with impaired renal function and / or body weight less than 70 kg

Maximum daily dose 1.0 g

Body mass (kg)	Creatinine clearance (ml / min / 1.73 m 2)
	≥71 kg	41-70	21-40	6-20
	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
	but 250 mg every 8 hours	125 mg every 6 hours	250 mg every 12 hours	125 mg every 12 hours
	125 mg every 6 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours
	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours	125 mg every 12 hours

Maximum daily dose 1.5 g

Body weight (kg)	Creatinine clearance (ml / min / 1.73 m 2)
	>71 kg	41-70	21-40	6-20
	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours
	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours
	125 mg every 6 hours	125 mg every 8 hours	125 mg every 8 hours	125 mg every 12 hours

Maximum daily dose 2.0 g

Body mass(kg)	Creatinine clearance a (ml / min / 1.73 m 2)
	≥71 kg	41-70	21-40	6-20
	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
	250 mg every 6 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours	250 mg every 12 hours
	250 mg every 8 hours	125 mg every 6 hours	125 mg every 8 hours	125 mg every 12 hours

Maximum daily dose 3.0 g

Body weight (kg)	Creatinine clearance (ml / min / 1.73 m 2)
	≥71 kg	41-70	21-40	6-20
	1000 mg every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
	750 mg every 8 hours	500 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours
	250 mg every 6 hours	250 mg every 8 hours	250 mg every 8 hours	250 mg every 12 hours

Maximum daily dose 4.0 g

Body weight (kg)	Creatinine clearance (ml / min / 1.73 m 2)
	≥71 kg	41-70	21-40	6-20
	1000 mg every 6 hours	750 mg every 8 hours	500 mg every 6 hours	500 mg every 12 hours
	1000 mg every 8 hours	750 mg every 8 hours	500 mg every 8 hours	500 mg every 12 hours
	750 mg every 8 hours	500 mg every 6 hours	500 mg every 8 hours	500 mg every 12 hours
	500 mg every 6 hours	500 mg every 8 hours	250 mg every 6 hours	250 mg every 12 hours
	500 mg every 8 hours	250 mg every 6 hours	250 mg every 8 hours	250 mg every 12 hours

With the introduction of a dose of 500 mg in patients with a creatinine clearance of 6-20 ml / min / 1.73 m 2, an increase in the risk of seizures is possible.

Imipenem + Cilastatin should not be administered intravenously to patients with creatinine clearance less than 5 ml / min / 1.73 m 2, unless hemodialysis is performed no later than 48 hours after the infusion of Imipenem + Cilastatin.

Hemodialysis

When treating patients with creatinine clearance less than 5 ml / min / 1.73 m 2 who are on hemodialysis, the recommendations on the dosing regimen of the drug Imipenem + Cilastatin for patients with creatinine clearance 6-20 ml / min / 1.73 m 2 should be applied ( see section "Dosing regimen for adult patients with impaired renal function").

Like imipenem, gak and cilastatin are eliminated during hemodialysis from the circulatory system. In connection with this, Imipenem + Cilastatin for intravenous infusion should be administered to patients after hemodialysis and then at 12-hour intervals from the end of the procedure. Patients on hemodialysis, especially if they have diseases of the central nervous system, should be closely monitored; the appointment of the drug Imipenem + Cilastatin in patients undergoing hemodialysis is recommended only in cases where the benefit of treatment outweighs the potential risk of seizures (see section "With caution").

There are currently insufficient data to recommend Imipenem + Cilastatin for intravenous injections patients on peritoneal dialysis.

The state of the kidneys in elderly patients cannot be fully determined only on the basis of measuring the level of residual nitrogen in the blood or creatinine. For the selection of dosages in such patients, it is recommended to determine the creatinine clearance.

Elderly patients

For elderly patients with normal renal function, dose adjustment is not required.

Impaired liver function

For patients with impaired liver function, dose adjustment is not required.

Prevention

Dosing regimen for adult patients

For the prevention of postoperative infections in adults, Imipenem + Cilastatin for intravenous infusion should be administered at a dose of 1 g at induction of anesthesia and then 1 g after 3 hours. In the case of high-risk surgery (for example, during operations on the colon and rectum), two additional doses of 500 mg should be administered 8 and 16 hours after induction of anesthesia.

Dosing schedule for children from 3 months of age

• Children weighing ≥40 kg should receive the same doses as adults.
• Children older than 3 months weighing less than 40 kg should receive the drug at a dose of 15 mg/kg at 6-hour intervals. The maximum daily dose should not exceed 2 g.

Preparation of solution for intravenous infusion

Imipenem + Cilastatin for intravenous infusion should not be mixed or added to other antibiotics..

Dosage form of the drug Imipenem + Cilastatin for intravenous infusion has a chemical incompatibility with lactic acid (lactate) and should not be prepared on the basis of solvents containing lactate. However, intravenous Imipenem + Cilastatin can be administered through the same infusion system as the solution containing lactate.

Imipenem + Cilastatin solution for intravenous infusion is prepared in accordance with Table 4 below. The final infusion solution must be shaken until a clear solution is obtained. The color of the solutions of the drug Imipenem + Cilastatin varies from colorless to yellow (color change within these limits does not affect the activity of the drug).

Table 4. Preparation of a solution of the drug Imipenem + Cilastatin for intravenous infusion

Dose of Imipenem + Cilastatin (mg imipenem)	Volume of added solvent (ml)	The average concentration of the infusion solution of the drug Imipenem + Cilastatin (mg/ml imipenem)

For bottle 20 ml, 25 ml

In the bottle with the drug Imipenem + Cilastatin, you must first add 10 ml of the appropriate solvent from the list presented in Table 5. The resulting primary suspension must be thoroughly shaken and added to the infusion bottle containing 90 ml of the infusion solvent.

THE PRIMARY SUSPENSION SHOULD NOT BE USED FOR INTRODUCTION.

For complete transfer of the drug, the procedure must be repeated. By adding 10 ml of the previously obtained solution from the infusion bottle to the bottle with the remnants of the powder.

The resulting suspension must be thoroughly shaken and added to an infusion bottle containing 90 ml of infusion solvent. The total volume of the solvent is 100 ml.

The final infusion solution must be shaken until a clear solution is obtained.

Table 5 presents data on the timing of the use of the infusion solution of the drug Imipenem + Cilastatin. prepared on the basis of a number of infusion solvents and stored at room temperature or in the refrigerator.

Table 5

Solvent	The shelf life of the drug
	Room temperature (25 °C)	Refrigerator
0.9% sodium chloride solution
5% dextrose solution
10% dextrose solution
5% dextrose solution and 0.9 % sodium chloride solution
5% dextrose solution and 0.45% sodium chloride solution
5% dextrose solution and 0.225% sodium chloride solution
5% dextrose solution and 0.15% potassium chloride solution
5% and 10% mannitol solution

Side effects:

In clinical studies, Imipenem + [Cilastatin] was administered intravenously to 1723 patients. The most common systemic side effects likely associated with the use of the drug were nausea (2.0%), diarrhea (1.8%), vomiting (1.5%), rash (0.9%), fever (0.5 %), lowering blood pressure (0.4%), convulsions (0.4%) (see section " special instructions"), dizziness (0.3%), itching (0.3%), urticaria (0.2%), drowsiness (0.2%).

The most common local adverse events were phlebitis, thrombophlebitis (3.1%), pain at the injection site (0.7%), erythema at the injection site (0.4%), and scarring of the vein wall (0.2%). Increases in serum transaminases and alkaline phosphatase have also been frequently reported.

The following are side effects registered in the course of clinical trials and in post-registration experience of use.

Reported side effects are classified by frequency: very often (≥14 0), often (≥1 / 100,<110), нечасто (≥1/1000, <1/100), редко (≥1/10000, <1 1000), очень редко (< 1/10000), частота неизвестна.

Rare: pseudomembranous colitis, candidiasis.

Very rare: gastroenteritis.

From the blood and lymphatic system

Often: eosinophilia.

Uncommon: pancytopenia, neutropenia, leukopenia, thrombocytopenia, thrombocytosis.

Rare: agranulocytosis.

Very rarely: hemolytic anemia, inhibition of the function of the red germ of the bone marrow.

From the side of the immune system

Rare: anaphylactic reactions.

From the side of the psyche

Infrequently: mental disorders, including hallucinations and states of confusion.

From the side of the nervous system

Uncommon: convulsions, myoclonus, dizziness, drowsiness.

Rare: encephalopathy, paresthesia, tremor, taste perversion.

Very rare: exacerbation of myasthenia gravis, headache.

Frequency unknown: agitation, dyskinesia.

On the part of the organ of hearing and labyrinth disorders

Rare: hearing loss.

Very rare: vertigo, ringing in the ears.

From the side of the heart

Very rare: cyanosis, tachycardia, palpitations.

From the side of the vessels

Often: thrombophlebitis.

Uncommon: lowering blood pressure.

Very rare: hot flashes.

From the respiratory system, chest organs and mediastinum

Very rare: shortness of breath, hyperventilation, sore throat.

From the gastrointestinal tract

Often: diarrhea, vomiting, nausea. Nausea and/or vomiting with Imipenem + [Cilastatin] has been more frequently observed in patients with gra-nullocytopenia.

Rare: staining of teeth and or tongue.

Very rarely: hemorrhagic colitis, abdominal pain, heartburn, glossitis, hypertrophy of the papillae of the tongue, hypersalivation.

From the side of the liver and biliary tract

Seldom: liver failure, hepatitis.

Very rare: fulminant hepatitis.

From the skin and subcutaneous tissues

Often: rash (including exanthematous).

Uncommon: urticaria, itching.

Rare: toxic epidermal necrolysis, angioedema, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis.

Very rare: hyperhidrosis, changes in skin structure.

From the musculoskeletal and connective tissue

Very rare: polyarthralgia, pain in the thoracic spine.

From the side of the kidneys and urinary tract

Rare: acute renal failure, oliguria/anuria, polyuria, urine discoloration (safe and should not be mistaken for hematuria). The role of imipenem + cilastatin] in changes in renal function is difficult to assess, since other factors are usually present that predispose to prerenal azotemia or deterioration of renal function.

From the genital organs and mammary gland

Very rare: genital itching.

General disorders and disorders at the injection site

Infrequently: fever, pain and induration at the injection site, erythema at the injection site.

Very rare: chest discomfort, asthenia/weakness.

Laboratory indicators

Often: increased activity of serum transaminases, increased activity of alkaline phosphatase.

Infrequently: a positive direct Coombs test, an increase in prothrombin time, a decrease in hemoglobin, an increase in serum bilirubin, an increase in serum creatinine, an increase in blood urea nitrogen.

Children (over 3 months old)

In a clinical study involving 178 children older than 3 months, the observed side effects were comparable to those reported in adult patients.

Overdose:

Overdose symptoms are consistent with the adverse reaction profile and may include convulsions, confusion, tremor, nausea, vomiting, low blood pressure, bradycardia.

There is no specific information on the treatment of drug overdose. sodium is excreted during hemodialysis, but the effectiveness of this procedure in case of an overdose of the drug is unknown.

Interaction:

The drug is pharmaceutically incompatible with lactic acid (lactate) and should not be prepared on the basis of solvents containing it. However, intravenously, the drug can be administered through the same infusion system as the solution containing lactate.

With simultaneous use with ganciclovir, the risk of developing generalized seizures increases. These drugs should not be used simultaneously, unless the potential benefits outweigh the possible risks.

Simultaneous use with probenecid is accompanied by a minimal increase in plasma concentration and half-life of imipenem. in this connection, the simultaneous use of probenecid and the drug is not recommended.

When using the drug with valproic acid or sodium divalproate, the plasma concentration of valproic acid decreases. As a result of this interaction, the concentration of valproic acid may fall below therapeutic levels, which increases the risk of seizures.

Although the mechanism of interaction is unknown, data invitro and the results of animal studies suggest that carbapenems may inhibit hydrolysis, as a result of which the glucuronide metabolite of valproic acid (VPA -g) is converted back to valproic acid, which leads to a decrease in the concentration of valproic acid in blood plasma (see section "Special Instructions" ).

The simultaneous use of antibacterial drugs with warfarin may enhance its anticoagulant effect. There are numerous reports of an increase in the anticoagulant effect of oral anticoagulants, including in patients taking antibacterial drugs at the same time.

The risk may vary depending on the infectious agent, age and general condition of the patient, so it is difficult to assess the effect of antibiotics on increasing the international normalized ratio (INR). It is recommended to periodically monitor the INR value during and immediately after the simultaneous use of antibacterial drugs with oral anticoagulants.

The drug should not be mixed in the same syringe with other antibiotics, while simultaneous - isolated - administration with other antibiotics (aminoglycosides) is allowed.

Special instructions:

Colors urine reddish (safe and should not be mistaken for hematuria).

Dosage form for intravenous administration should not be used for intramuscular injection.

There is evidence of partial cross-allergy when using the drug and other beta-lactam antibiotics - penicillins and cephalosporins. Before starting therapy, a thorough history should be taken for previous allergic reactions to beta-lactam antibiotics. With the development of an allergic reaction, the drug should be immediately discontinued and appropriate measures taken.

When using the drug with valproic acid or sodium divalproate, the plasma concentration of valproic acid decreases, which leads to a decrease in the effectiveness of anticonvulsant therapy. Increasing the dose of valproic acid or sodium divalproate may not be sufficient to overcome the effects of the interaction. The concomitant use of imipenem and valproic acid/sodium divalproate is not recommended. Treatment of infections with antibacterial drugs of other groups (not carbapenems) should be considered in patients receiving anticonvulsant therapy with valproic acid or sodium divalproate. If necessary, the use of the drug may require additional anticonvulsant therapy.

Pseudomembranous colitis can develop with almost all antibacterial drugs, which can range in severity from mild to life-threatening. In this regard, patients with a history of diseases of the gastrointestinal tract, especially colitis, antibiotics should be prescribed with caution. It is important to consider the diagnosis of pseudomembranous colitis in patients presenting with diarrhea after antibiotic use. Although studies show that the main cause of "antibiotic-associated colitis" is a toxin produced by Clostridiumdifficile, other possible causes should be taken into account. If pseudomembranous colitis is suspected or confirmed, consideration should be given to discontinuing drug therapy and conducting specific therapy. Do not use drugs that inhibit intestinal motility.

As with other beta-lactam antibiotics, Rseudo topsaeruginosa can quickly acquire resistance to imipenem. Therefore, in the course of treatment, it is necessary to periodically determine the sensitivity Pseudomonas aeruginosa to an antibiotic according to a clinical situation.

In order to prevent the development of resistance and maintain the effectiveness of imipenem in clinical practice, the drug should be used only for the treatment of infections caused by proven (or suspected) microorganisms susceptible to imipenem. If there is information about the identified pathogen and its sensitivity to antibiotics, the doctor is guided by it to select the optimal antibiotic, and in the absence of such, the empirical choice of an antibacterial drug is based on regional epidemiological data and sensitivity data.

Due to the risk of developing liver toxicity (increased activity of "liver" transaminases, liver failure, fulminant hepatitis), when using the drug, liver function should be carefully monitored.

In patients with liver disease, the state of liver function should be monitored during the period of drug use. Dose adjustment is not required.

As with other beta-lactam antibiotics, there have been reports of adverse reactions from the central nervous system (CNS): myoclonus, confusional states and convulsions, especially in cases where the recommended doses were exceeded, taking into account kidney function and weight. body. Usually, such phenomena were observed in patients with CNS damage (brain injury or convulsions in history) and / or in patients with impaired renal function, in which drug accumulation is possible. In this regard, especially in such patients, it is imperative to strictly adhere to the recommended doses (see section "Method of application and doses").

In patients with seizure disorders, anticonvulsant therapy should be continued.

If tremor, myoclonus, or seizures occur, patients should be referred for neurologic evaluation and anticonvulsant therapy should be instituted if it has not already been started. If symptoms from the CNS persist, then the dose of the drug should be reduced or discontinued.

The drug should not be used in patients with creatinine clearance ≤ 5 ml / min / 1.73 m 2, unless hemodialysis is performed no later than 48 hours after the infusion of the drug. The use of the drug in patients undergoing hemodialysis is recommended only in cases where the benefit of treatment outweighs the potential risk of seizures.

In children older than 3 months, the drug is used for the same indications as in adult patients.

Data on the efficacy and safety of the use of imipenem cilastatin for intravenous administration in children under 3 months of age and with impaired renal function (serum creatinine more than 2 mg / dl) are not enough.

The dosage form contains 35.7 mg (1.55 meq) of sodium.

Influence on the ability to drive transport. cf. and fur.:

Studies on the effect of the drug on the ability to drive vehicles, mechanisms were not carried out. Some side effects associated with the use of the drug (for example, hallucinations, dizziness, drowsiness and vertigo) may affect the ability to drive vehicles and operate machines.

Release form / dosage:

Powder for solution for infusion, 500 mg + 500 mg.

Package:

500 mg + 500 mg of active ingredients in glass tube vials for drugs with a capacity of 20 ml or 25 ml, hermetically sealed with rubber stoppers, crimped with aluminum caps or 500 mg + 500 mg of active ingredients in glass bottles for blood, infusion and transfusion preparations with a capacity of 100 ml, corked with rubber stoppers and crimped with aluminum caps.

1, 5 or 10 bottles with the drug with a capacity of 20 ml or 25 ml are placed in individual cardboard packs along with instructions for use.

1 bottle with the drug with a capacity of 100 ml is placed in an individual cardboard box along with instructions for use.

25 vials with a preparation with a capacity of 20 ml or 25 ml with instructions for use corresponding to the number of vials are placed in a cardboard box for consumer packaging (for hospitals).

35 bottles with the drug with a capacity of 100 ml are placed in corrugated cardboard boxes with instructions for use corresponding to the number of bottles (for hospitals).

Storage conditions:

In a place protected from light, at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Best before date:

3 years.

Do not use after the expiration date.