Cilastatin sodium. Dosage form Imipenem with cilastatin: powder for solution for intramuscular injection
International name
Imipenem+[Cilastatin] (Imipenem+)Group affiliation
Antibiotic carbapenem + dehydropeptidase inhibitorDosage form
Powder for solution for intramuscular injection, powder for solution for infusion, powder for solution for intravenous administrationpharmachologic effect
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.
Susceptible in vivo: Gram-positive aerobes - Enterococcus faecalis, Staphylococcus aureus, including penicillinase-forming strains, Staphylococcus epidermidis, including penicillinase-forming strains, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes.
Gram-negative aerobes: 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 S. marcescens.
Gram-positive anaerobes: Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp.
Gram-negative anaerobes: Bacteroides spp., including B. fragilis, Fusobacterium spp.
Sensitive in vitro (clinical efficacy not established): gram-positive aerobes - Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus saprophyticus, Streptococcus spp. groups C, G and viridans.
Gram-negative aerobes: Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducreyi, Neisseria gonorrhoeae, including penicillinase-producing strains, Pasteurella spp., Providencia stuartii.
Gram-negative anaerobes: 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.
Indications
For intravenous administration - treatment of severe infections caused by susceptible microorganisms: infections of the lower respiratory tract, urinary tract (complicated and uncomplicated), intra-abdominal and gynecological infections, septicemia, infections of bones and joints, skin and subcutaneous tissues, endocarditis, super- and co - infections.
For i / m administration - treatment of mild and moderate infections caused by susceptible microorganisms: infections of the lower respiratory tract, intra-abdominal and gynecological infections, infections of the skin and subcutaneous tissues.
Contraindications
Hypersensitivity (including to carbapenems and other beta-lactam antibiotics), pregnancy (only for "vital" indications); CRF (CC less than 5 ml / min without hemodialysis), CRF in children weighing less than 30 kg, CNS infections in children.
For a suspension for intramuscular injection prepared using lidocaine as a solvent - hypersensitivity to local anesthetics of the amide structure (shock, impaired intracardiac conduction).
Additionally for i / m administration: children under 12 years of age.
Side effects
From the nervous system: myoclonus, mental disorders, hallucinations, confusion, convulsions, paresthesia, dizziness, drowsiness, encephalopathy, tremor, headache, vertigo.
From the senses: hearing loss, tinnitus, taste disturbance.
From the urinary system: oliguria, anuria, polyuria, acute renal failure (rarely), changes in urine color.
From the digestive system: nausea, vomiting, diarrhea, pseudomembranous colitis, hemorrhagic colitis, hepatitis (rarely), liver failure, jaundice, gastroenteritis, abdominal pain, glossitis, hypertrophy of the papillae of the tongue, staining of the teeth or tongue, pain in the throat, hypersalivation.
On the part of the hematopoietic organs: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, pancytopenia, depression of bone marrow hematopoiesis, hemolytic anemia.
Laboratory indicators: increased activity of "liver" transaminases and alkaline phosphatase, LDH, hyperbilirubinemia, hypercreatininemia, increased concentration of urea nitrogen; direct false positive Coombs test; decrease in Hb and hematocrit, prolongation of prothrombin time; hyponatremia, hyperkalemia, hyperchloremia; the appearance of protein, erythrocytes, leukocytes, cylinders in the urine.
Allergic reactions: skin rash, itching, urticaria, erythema multiforme, Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis (rarely), exfoliative dermatitis (rarely), fever, anaphylactic reactions.
From the CCC: lowering blood pressure, palpitations, tachycardia.
Local reactions: skin hyperemia, painful infiltrate at the injection site, thrombophlebitis.
Others: candidiasis, vaginal itching, cyanosis, hyperhidrosis, polyarthralgia, asthenia, burning behind the sternum.
Application and dosage
In/in drip and/m. Doses are given in terms of imipenem.
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. infections of the lower respiratory tract caused by Pseudomonas aeruginosa, and in case of severe complications.
To prepare the infusion solution, 100 ml of a solvent (0.9% NaCl solution, 5% aqueous dextrose solution, 10% aqueous dextrose solution, 5% dextrose solution and 0.9% NaCl, etc.) is added to the vial. The concentration of imipenem in the resulting solution is 5 mg/ml.
Each 250-500 mg is administered intravenously over 20-30 minutes, and every 750-1000 mg over 40-60 minutes. If nausea occurs during administration, the rate of administration of the drug is reduced.
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.
Dosing regimen in patients weighing 70 kg or more and CC 71 (ml / min / 1.73 sq.m.): with high sensitivity of pathogens, including gram-positive and gram-negative aerobes and anaerobes: mild severity - 250 mg every 6 hours ( total daily dose 1 g); medium degree - 500 mg every 6 or 8 hours (total daily dose of 2 g or 1.5 g); life-threatening infections - 500 mg every 6 hours (total daily dose of 1 g); uncomplicated urinary tract infections - 250 mg every 6 hours (total daily dose of 1 g); complicated urinary tract infections - 500 mg every 6 hours (total daily dose of 2 g).
With moderate sensitivity of pathogens, mainly some strains of Pseudomonas aeruginosa: mild severity - 500 mg every 6 hours (total daily dose of 2 g); medium degree - 500 mg every 6 hours (total daily dose 2 g) or 1000 mg every 8 hours (total daily dose 3 g); life-threatening infections - 1000 mg every 6 or 8 hours (total daily dose of 4 g or 3 g); uncomplicated urinary tract infections - 250 mg every 6 hours (total daily dose of 1 g); complicated urinary tract infections - 500 mg every 6 hours (total daily dose of 2 g).
In view of the high antimicrobial activity of the drug, the dose should not be administered more than 50 mg / kg / day or 4 g / day. Patients over 12 years of age with cystic fibrosis were prescribed up to 90 mg / kg / day, but not more than 4 g / day.
Adults weighing less than 70 kg or with CC less than 71 (ml / min / 1.73 sq.m.): First, it is necessary to determine the total daily dose appropriate for patients with a body weight of 70 kg and in the absence of chronic renal failure. When used in a total daily dose of 1 g / day: with a CC of more than 71 ml / min / 1.73 sq.m and a body weight of more than 70 kg - 250 mg every 6 hours; with CC more than 71 and body weight 60 kg - 250 mg every 8 hours; with CC more than 71 and body weight 40-50 kg - 125 mg every 6 hours; with CC more than 71 and body weight 30 kg - 125 mg every 8 hours. With CC 41-70 and body weight more than 70 kg - 250 mg every 8 hours; with CC 41-70 and body weight 50-60 kg - 125 mg every 6 hours; with CC 41-70 and body weight 50-60 kg - 125 mg every 8 hours. With CC 21-40 and body weight over 60 kg - 250 mg every 12 hours; with CC 21-40 and body weight 50 kg - 125 mg every 8 hours; with CC 21-40 and body weight 30-40 kg - 125 mg every 12 hours. With CC 6-20 and body weight over 70 kg - 250 mg every 12 hours; with CC 6-20 and body weight 30-60 kg - 125 mg every 12 hours.
When administered in a total daily dose of 1.5 g / day: with CC over 71 and body weight over 70 kg - 500 mg every 8 hours; with CC more than 71 and body weight 50-60 kg - 250 mg every 6 hours; with CC more than 71 and body weight 40 kg - 250 mg every 8 hours; with CC more than 71 and body weight 30 kg - 125 mg every 6 hours. With CC 41-70 and body weight more than 70 kg - 250 mg every 6 hours; with CC 41-70 and body weight 50-60 kg - 250 mg every 8 hours; with CC 41-70 and body weight over 40 kg - 125 mg every 6 hours; with CC 41-70 and body weight 30 kg - 125 mg every 8 hours. With CC 21-40 and body weight over 60 kg - 250 mg every 8 hours; with CC 21-40 and body weight 50 kg - 250 mg every 12 hours; with CC 21-40 and a body weight of 30-40 kg - 125 mg every 8 hours. With CC 6-20 and a body weight of more than 50 kg - 250 mg every 12 hours; with CC 6-20 and body weight 30-40 kg - 125 mg every 12 hours.
When administered in a total daily dose of 2 g / day: with CC over 71 and body weight over 70 kg - 500 mg every 6 hours; with CC more than 71 and body weight 60 kg - 500 mg every 8 hours; with CC more than 71 and body weight 40-50 kg - 250 mg every 6 hours; with CC more than 71 and a body weight of 30 kg - 250 mg every 8 hours. With CC 41-70 and a body weight of more than 70 kg - 500 mg every 8 hours; with CC 41-70 and body weight 50-60 kg - 250 mg every 6 hours; with CC 41-70 and body weight 40 kg - 250 mg every 8 hours; With CC 41-70 and a body weight of 30 kg - 125 mg every 6 hours. With CC 21-40 and a body weight of more than 70 kg - 250 mg every 6 hours; with CC 21-40 and body weight 50-60 kg - 250 mg every 8 hours; with CC 21-40 and body weight 40 kg - 250 mg every 12 hours; with CC 21-40 and a body weight of 30 kg - 125 mg every 8 hours. With CC 6-20 and a body weight of more than 40 kg - 250 mg every 12 hours; with CC 6-20 and body weight 30 kg - 125 mg every 12 hours.
When administered in a total daily dose of 3 g / day: with CC over 71 and body weight over 70 kg - 1000 mg every 8 hours; with CC more than 71 and body weight 60 kg - 750 mg every 8 hours; with CC more than 71 and body weight 50 kg - 500 mg every 6 hours; with CC more than 71 and body weight 40 kg - 500 mg every 8 hours; with CC more than 71 and body weight 30 kg - 250 mg every 6 hours. With CC more than 41-70 and body weight more than 70 kg - 500 mg every 6 hours; with CC more than 71 and body weight 50-60 kg - 500 mg every 8 hours; with CC more than 71 and body weight 40 kg - 250 every 6 hours; with CC more than 71 and body weight 30 kg - 250 mg every 8 hours. With CC 21-40 and body weight more than 60 kg - 500 mg every 8 hours; with CC 21-40 and body weight 50 kg - 250 mg every 6 hours; with CC 21-40 and body weight 30-40 kg - 250 mg every 8 hours. With CC 6-20 and body weight over 60 kg - 500 mg every 12 hours; with CC 6-20 and body weight 30-50 kg - 250 mg every 12 hours.
When administered in a total daily dose of 4 g / day: with CC over 71 and body weight over 70 kg - 1000 mg every 6 hours; with CC more than 71 and body weight 60 kg - 1000 mg every 8 hours; with CC more than 71 and body weight 50 kg - 750 mg every 8 hours; with CC more than 71 and body weight 40 kg - 500 mg every 6 hours; with CC more than 71 and a body weight of 30 kg - 500 mg every 8 hours. With CC 41-70 and a body weight of more than 60 kg - 750 mg every 8 hours; with CC 41-70 and body weight 50 kg - 500 mg every 6 hours; with CC 41-70 and body weight 40 kg - 500 mg every 8 hours; with CC 41-70 and a body weight of 30 kg - 250 mg every 6 hours. With CC 21-40 and a body weight of more than 70 kg - 500 mg every 6 hours; with CC 21-40 and body weight 50-60 kg - 500 mg every 8 hours; with CC 21-40 and body weight 40 kg - 250 mg every 6 hours; with CC 21-40 and a body weight of 30 kg - 250 mg every 8 hours. With CC 6-20 and a body weight of more than 50 kg - 500 mg every 12 hours; with CC 6-20 and body weight 30-40 kg - 250 mg every 12 hours.
Patients with CC 6-20 in most cases are prescribed 125-250 mg every 12 hours, because. when prescribing 500 mg every 12 hours, the risk of seizures increases.
For patients with CC less than 6 ml / min / 1.73 sq.m, the drug is prescribed if they undergo hemodialysis for 48 hours, while the doses correspond to those prescribed for patients with CC 6-20 ml / min / 1.73 sq.m. Imipenem and cilastatin are removed during hemodialysis, so the drug is administered after the procedure and then at intervals of 12 hours. For patients with CNS infections on hemodialysis, the drug is prescribed if the expected benefit outweighs the risk.
Children older than 3 months are prescribed at a dose of 15-25 mg / kg every 6 hours (with the exception of CNS infections). With high sensitivity of pathogens, the total daily dose should not exceed 2 g, with moderate sensitivity of the pathogen - 4 g. Doses of more than 90 mg / kg / day are prescribed for cystic fibrosis.
Children under 3 months (weighing more than 1500 g): in the early neonatal period (up to 7 days) - 25 mg / kg every 12 hours; in the late neonatal period (8-28 days) - 25 mg / kg every 8 hours; at the age of 1-3 months - 25 mg / kg every 6 hours. A dose of up to 500 mg is administered within 15-30 minutes, more than 500 mg - within 40-60 minutes.
Children with infections of the central nervous system or chronic renal failure (weighing less than 30 kg) are not prescribed the drug.
When i / m administration to patients with infections of the lower respiratory tract, skin and subcutaneous tissues and gynecological infections with mild and moderate severity of the disease, depending on the severity, 500-750 mg is prescribed every 12 hours. For intra-abdominal infections, 750 mg is prescribed every 12 hours The drug is injected deep into a large muscle with a needle of at least 21 in size and 2 in diameter. 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. .
The maximum daily dose is 1500 mg.
Treatment should be continued for another 2 days after the resolution of the symptoms of the disease. The efficacy and safety of treatment after 14 days of use, as well as in patients with CC less than 20 ml / min / 1.73 sq.m, has not been studied.
special instructions
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 colitis.
Therapy with antiepileptic drugs in patients with a history of brain injury or seizures should continue for the entire period of treatment with the drug (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.
Interaction
Pharmaceutically incompatible with lactic acid salts, 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.
Significantly reduces the concentration of vaplproic acid in the blood, which can reduce the effectiveness of ongoing anticonvulsant therapy.
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).
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Do you use imipenem with cilastatin as an analogue or vice versa?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 plasma 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. It is found in low concentrations in the cerebrospinal fluid (CSF). 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:
- infections of the lower respiratory tract;
- urinary tract infections;
- intra-abdominal infections;
- gynecological infections;
- bacterial septicemia;
- infections of bones and joints;
- infections of the skin and soft tissues;
- bacterial endocarditis.
Prevention of postoperative infectious complications.
Dosing regimen
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 S h | 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 mi 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 effect
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; increase in the 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: decrease in 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.
Contraindications for use
- 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 with valproic acid (reducing the effectiveness of therapy), old age.
Use during pregnancy and lactation
Use during pregnancy is only permissible if the possible benefit 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.
Use in children
Contraindicated in early childhood (up to 3 months); in children - with severe renal failure (serum creatinine concentration more than 2 mg / dl)
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 ganciclovir, the risk of developing generalized seizures increases. 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, the use of these drugs at the same time is not recommended).
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 treatment period, it is recommended to monitor the serum concentration of valproic acid.
Terms of dispensing from pharmacies
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.
Application for violations of kidney function
contraindicated in chronic renal failure with CC less than 5 ml / min / 1.73 m 2 without hemodialysis
Use in elderly patients
The drug should be used with caution in elderly patients
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 of an allergic reaction, the drug should be immediately discontinued.
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 is indicated. Do not use drugs that inhibit intestinal motility.
As with other beta-lactam antibiotics, Pseudomonas aeruginosa can develop drug resistance 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.
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 injection was determined in the vitreous body of the 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.; urinary tract infections 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 surgery 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 reduced functions of the liver, kidneys, cardiovascular system, characteristic of this age group, the presence of concomitant diseases and concomitant drug treatment, care must be taken when choosing a dose, adhering to the lower limits of the recommended doses. In these patients, monitoring of the excretory function of the kidneys is recommended.
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 of pseudomembranous colitis of clostridial etiology) may develop, 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 of an antibacterial agent is carried out on the basis of sensitivity data and based on 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 increased production of toxins cause the most severe cases that are resistant to any antibiotic 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 metabolism parameters, fluid and electrolyte balance, suppress Clostridium difficile infection, and also 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), breastfeeding period.
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 be used during pregnancy only when the expected benefit to the mother outweighs the potential risk to the fetus. During therapy with imipenem, it is necessary to stop breastfeeding (imipenem is excreted in 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, pain in the 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 the thoracic 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, 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 creatinine and urea.
Others: candidiasis, increased plasma concentration of potassium, decreased serum concentrations 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.
Some infectious diseases are not so easy to defeat. They can not only seriously impair the state of health, but even create a real threat to the life of the patient. In such cases, truly high-quality and effective medicines should be used that can successfully defeat a dangerous infection and restore health. To combat various infectious diseases, Imipenem + Cilastatin is often used. According to the reviews of patients and doctors, it is incredibly effective. Before deciding to start treatment with the drug in question, it is necessary to find out as much information as possible about the drug "Imipenem + Cilastatin": the trade name of the drug, the features of the action and the method of its use. Who needs to use the medication in question? What are the contraindications? What adverse reactions can be expected? You can find out all this information by reading this article.
Compound
The composition of the drug "Imipenem + Cilastatin" includes an equal combination of cilastatin (which is an inhibitor of the enzyme dihydropeptidase of the kidneys) and sodium salts of imipenem (antibiotic). One vial of the drug, as a rule, contains five hundred milligrams of both substances.
Release form
The considered drug "Imipenem + Cilastatin" is available in the form of a powder for injection (for intravenous administration) in vials of various volumes, namely: sixty and one hundred and twenty milliliters. This powder must be dissolved in sodium bicarbonate.
In the case when the drug is prescribed for intramuscular injection, vials containing 0.5 or 0.75 grams of imipenem and cilastatin should be purchased (depending on the dosage that was prescribed to the patient by the attending physician).
Indications for use
The drug "Imipenem + Cilastatin" is prescribed for use by patients in the presence of infectious and inflammatory diseases that were caused by any microorganisms sensitive to the action of the main active substances of the drug, which include both polymicrobial and mixed aerobic-anaerobic infections (these include infectious diseases of the urinary tract and lower respiratory tract, sepsis, infectious diseases of the joints and bones, peritonitis, intra-abdominal infections, inflammatory processes that occur in the pelvic organs, various infectious diseases of the skin and soft tissues, as well as endocarditis.Also, the drug is effectively used as a prophylaxis development of complications after surgery.
pharmachologic effect
The effectiveness of the drug "Imipenem + Cilastatin" is due to the successful combination of two active ingredients. The first, imipenem, is a special beta-lactam antibiotic that actively destroys pathogenic bacteria (thus having a bactericidal effect). This substance has a fairly wide spectrum of action. And this means that many pathogenic microorganisms are sensitive to its effects. The second component, cilastatin sodium, actively influencing the enzyme that decomposes imipenem in the kidneys of the patient's body, suppresses its action, which contributes to a sufficient increase in the concentration of the above antibiotic in unchanged form in the patient's body. Consequently, the overall effectiveness of the drug "Imipenem + Cilastatin" increases many times over.
Application
To achieve the greatest effect and to avoid any negative consequences of therapy, it is important to carefully adhere to the recommendations regarding the use of the drug. The drug "Imipenem and Cilastatin Jodas" is injected into the patient's body intravenously (drip).
Despite the fact that the instructions suggest average doses for the use of the drug, before starting treatment, it is important to adjust the treatment regimen directly with the attending physician, who can correctly establish the appropriate dosage, taking into account all the individual characteristics of the patient and his anamnesis.
The doses that the instructions for the use of the substance in question contain for the drug "Imipenem + Cilastatin" are intended for those patients whose body weight exceeds seventy kilograms. For those patients whose body weight is less, the working dose of the drug should be proportionally reduced (it is important that this process be led by a competent specialist).
For an adult patient, the average daily dose of the drug "Imipenem and Cilastatin Jodas" is one to two grams, provided it is divided into three to four injections. At the same time, the maximum dose that is acceptable for administration within one day is four grams or fifty milligrams per kilogram of body weight (the choice should fall on the smaller of these two acceptable doses).
Doses also vary depending on the severity of the disease. So, if we are talking about a patient with a mild infection, then the working dose of the drug for him will be two hundred and fifty milligrams (injections should be repeated four times a day). If the severity is moderate, then the amount of the drug for a single injection should be five hundred milligrams. The drug should be administered three times a day. If the infection is severe, then this dose of the drug should be applied four times a day. When the patient's condition is so serious that there is a serious threat to his life, one gram should be administered three to four times a day. The drug should be administered slowly (gram within an hour, two hundred and fifty - five hundred milligrams - within twenty to thirty minutes).
If the drug is used to prevent postoperative infections, it is important to administer one gram during anesthesia and the same dose three hours later.
If during the operation there is a threat of developing any infection (especially for operations on the rectum and colon), "Imipenem + Cilastatin" instructions for use recommends administering five hundred milligrams eight and sixteen hours after anesthesia.
In order to prepare a working solution, it is necessary to add one hundred milliliters of a specialized solvent to the vial with the powder of the substance, which includes a five percent or ten percent aqueous dextrose solution, 0.9% sodium chloride solution. In such a solution, the concentration of the antibiotic imipenem should be no more than five milligrams per milliliter.
You should not use the drug in question simultaneously with other antibacterial drugs, as well as with a lactic acid salt.
The substance is incompatible with other beta-lactam antibiotics (these include cephalosporin, monobactam and penicillin). Their simultaneous use can lead to cross-allergic reactions.
Interaction with ganciclovir sometimes provokes the development of generalized seizures.
Various substances that block tubular secretion increase the plasma concentration of imipenem, as well as its half-life. Thus, if the administration of this substance in high doses is required for effective treatment, then these groups of substances should not be used simultaneously.
It is forbidden to use the drug in question during the period of bearing a child, as well as during breastfeeding.
This drug should not be used to treat meningitis.
Urine during therapy may be slightly reddish in color.
Dosage forms of the drug (for intravenous administration and for intramuscular administration) should be used strictly for the intended purpose. They are not interchangeable. Before starting treatment with the drug in question, it is important to conduct a thorough investigation for the occurrence of allergic reactions or increased individual sensitivity to beta-lactam antibiotics.
If the patient already had other diseases of the gastrointestinal tract, for example, colitis, then when using the drug in question, there is a possibility of developing pseudomembranous enterocolitis.
In order to successfully avoid the occurrence of any unpleasant reactions from the central nervous system in those patients who have had any brain injury or suffered from convulsions, it is recommended to conduct concomitant therapy with high-quality antiepileptic drug substances.
It should be borne in mind that elderly patients are likely to have age-related renal dysfunction, which may require dose reduction.
It is important to remember that elderly patients should use the drug with caution. As a rule, they show symptoms of various age-related disorders in the functioning of the kidneys. In this case, if it is necessary to use the drug "Imipenem + Cilastatin", the instructions for use recommend that you consult with your doctor about reducing the dose of the drug used.
There are some special conditions for the use of the medication in question for children. If their body weight exceeds forty kilograms, then the same recommendations may apply to them as to adult patients. If the child is older than three months, and his weight is less than forty kilograms, then the maximum daily dose of such a patient will be two grams. They should enter fifteen milligrams per kilogram four times a day.
In no case should you use the drug "Imipenem + Cilastatin" for children who have not yet reached three months, as well as for those babies who have impaired normal kidney function, which can be expressed in a serum creatinine concentration level above two milligrams per deciliter.
Contraindications
There are some nuances that must be considered when using Imepenem + Cilastatin. The instruction recommends that you carefully study the contraindications to this drug. And among them are the following:
- the period of bearing a child;
- breastfeeding period;
- children's age up to three months;
- children who suffer from impaired renal function associated with a high concentration of serum creatinine;
- individual sensitivity to individual components of the drug in question, as well as to other beta-lactam antibiotics and carbapenems.
It is important to bear in mind that elderly patients, as well as those who suffer or have ever suffered from diseases of the central nervous system or diseases of the gastrointestinal tract, should take the drug with caution under the constant guidance of the attending physician. It is he who will be able to competently prescribe the correct dosage of the drug "Imipenem + Cilastatin". It is important to study contraindications before starting treatment.
Side effects
It is important to know one more nuance about the "Imipenem + Cilastatin" remedy. The formula of the drug is such that some patients may experience some adverse reactions from various body systems. Among them are: thrombophlebitis, taste disturbance, candidiasis, oliguria, myoclonus, hallucinations, paresthesias, confusion, acute renal failure, mental disorders, epileptic seizures, polyuria, anuria, indigestion, hepatitis, nausea and vomiting, leukopenia, pseudomembranous enterocolitis, lymphocytosis, hyperbilirubinemia, eosinophilia, pruritus, leukopenia, skin rash, thrombocytosis, hypercreatininemia, monocytosis, urticaria, basophilia, direct positive Coombs test.
There is no precise information on how to manage an overdose of the drug in question. However, it is known that these active substances are successfully subjected to hemodialysis. However, it is still unknown how effective this procedure is in case of overdose. Therefore, it is important to follow all the recommendations that the description of this drug contains for the use of Imipenem + Cilastatin.
Storage conditions
In order for the use of the drug to be effective, it is important to consider another important point. Namely, how to store the drug "Imipenem + Cilastatin". The description of the substance contains the following tips.
The powder must be kept in a room that maintains room temperature. Ready working solution should be used no later than one hour after production. Solutions of sodium chloride at room temperature can be stored for no more than ten hours, and in the refrigerator - no more than forty-eight. Glucose solutions can be stored for no more than four and twenty-four hours, respectively.
Analogues
There are a number of drugs that are included in the group of analogues of the drug "Imipenem + Cilastatin". Substitutes for the drug in question are Inempplus, Mixacil, Lastinem, Sinerpen, Tiaktam, Piminam, Supranem and Tienam. As a rule, all these drugs have the same active substance as the drug in question. The main active substances of these drugs are imipenem, cilastatin (the trade name of which reflects the above medicines). Thus, for these medicines, in general, contraindications, side effects, and pharmacological effects coincide. However, it should be remembered that the dosage should be prescribed by the attending physician, who can take into account all the necessary nuances. The drug "Imipenem + Cilastatin", drug analogues should not be used by patients without permission, without the appointment of the attending physician and his constant monitoring. Including his consultation is also necessary when choosing an appropriate analogue.
Generalization
Practice confirms the effectiveness of the drug "Imipenem + Cilastatin". Reviews report successful treatment results. However, both doctors and patients emphasize that it is important to strictly adhere to the recommendations contained in the instructions and provided by the attending physician. Only such a method of implementing therapy can benefit the patient's body.
Contraindications should not be ignored, the presence of which does not allow starting treatment with the drug in question. Otherwise, its use may not only not give a positive result, but also cause serious harm to the physical condition of the patient. Also, improper use of the drug in question can lead to side effects, some of which can significantly aggravate the patient's condition. It is important that the treatment is carried out under the supervision of a competent physician who is not only well acquainted with the use of this medicinal product, but also possesses the necessary skills and knowledge in order to cope with unexpectedly arising difficult situations. Your health should be in the hands of real professionals.
Before deciding to start treatment with the drug in question, it is important to carefully read all the information about it, which reflects the features of its effect on the body. It is necessary to know everything about potential adverse reactions, the occurrence of which can cause a lot of inconvenience to the patient and difficulties to his attending physician.
It is important to treat the choice of a method of treatment as responsibly as possible. Choose the highest quality drugs!
Description
Powder from white to pale yellow.
Composition for 1 bottle
dosage 250 mg/250 mg
250 mg Imipenem/250 mg Cilastatin and sodium bicarbonate
dosage 500 mg/500 mg
500 mg Imipenem/500 mg Cilastatin and sodium bicarbonate
Pharmacotherapeutic group
Antibiotic of the carbapenem group.
ATX code: J01DH51.
Pharmacological properties
Pharmacodynamics
Imicinem-TF is a broad-spectrum antibiotic consisting of two components.
Imipenem inhibits the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative pathogens, aerobic and anaerobic.
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.
The antimicrobial spectrum of Imicinem-TF includes virtually all clinically significant pathogens. In vitro antibiotic active against aerobic gram-negative bacteria: Achromobacter spp., Acinetobacter spp. (formerly Mima-Herellea), Aeromonas hydrophila, Alcaligenes spp., Bordetella bronchicanis, Bordetella bronchiseptica, Bordetella pertussis, Brucella melitensis, Campylobacter spp., Capnocytophaga spp., Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii), Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae (including beta-lactamase producing strains), Haemophilus ducreyi, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella spp. (including Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella ozaenae), Moraxella spp., Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including strains that produce penicillinase), Neisseria meningitidis, Pasteurella multocida, Proteus spp. (including Proteus mirabilis, Proteus vulgaris), Plesiomonas shigelloides, Providencia spp. (including Providencia rettgeri /formerly Proteus rettgeri/, Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudomallei, Pseudomonas putida, Pseudomonas stutzeri), Salmonella spp. (including Salmonella typhi), Serratia spp. (including Serratia proteamaculans /formerly Serratia liquefaciens/, Serratia marcescens), Shigella spp., Yersinia spp. (including Yersinia enterocolitica, Yersinia pseudotuberculosis); aerobic gram-positive bacteria: Bacillus spp. Enterococcus faecalis Erysipelothrix rhusiopathiae Listeria monocytogenes Nocardia spp. Pediococcus spp. group B (including Streptococcus agalactiae), Streptococcus spp. groups C, G, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans (including hemolytic alpha and gamma strains); anaerobic Gram-negative bacteria: Bacteroides spp., Bacteroides distasonis, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaomicron, Bacteroides uniformis, Bacteroides vulgatus, Bilophila wadsworthia, Fusobacterium spp., Fusobacterium necrophorum, Fusobacterium nucleatum, Porphyromonas asaccharolytica (ранее Bacteroides asaccharolytica), Prevotella bivia (ранее Bacteroides bivius) , Prevotella disiens (formerly Bacteroides disiens), Prevotella intermedia (formerly Bacteroides intermedius), Prevotella melaninogenica (formerly Bacteroides melaninogenicus), Veillonella spp.; anaerobic gram-positive bacteria: Actinomyces spp., Bifidobacterium spp., Clostridium spp. (including Clostridium perfringens), Eubacterium spp., Lactobaccilus spp., Mobilincus spp., Microaerophilic streptococcus, Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp. (including Propionibacterium acnes); others: Mycobacterium fortuitum, Mycobacterium smegmatis.
To Imitsinem-TF resistant Xanthomonas maltophilia (formerly Pseudomonas maltophilia) and some strains of Pseudomonas cepacia, as well as Streptococcus faecium and methicillin-resistant staphylococci.
In vitro tests show that the antibiotic acts synergistically with antibiotics from the aminoglycoside group against certain isolates of Pseudomonas aeruginosa.
Imicinem-TF is effective alone or in combination with other antimicrobial agents in the treatment of polymicrobial infections.
Pharmacokinetics
Distribution
After intravenous administration, the bioavailability of imipenem is 98%. The antibiotic is well distributed, creating high concentrations in various tissues and body fluids. Plasma protein binding is 20%.
Metabolism and excretion
Imipenem is metabolized in the kidneys by hydrolysis of the beta-lactam ring by renal dehydropeptidase. The half-life of imipenem is 1 hour.
Pharmacokineticsin special clinical situations
In case of impaired renal function, as well as in the elderly (over 65 years), there is a decrease in total and renal clearance and an increase in the half-life of imipenem.
Indications for use
Polymicrobial and mixed aerobic-anaerobic infections, empiric therapy prior to identification of pathogens.
Infections caused by strains of microorganisms sensitive to the drug: pneumonia (including nosocomial), infections of the urinary system, infections of the abdominal cavity, gynecological infections, infections of the skin and soft tissues, septicemia, infections of bones and joints, infective endocarditis, mixed infections.
Before using the drug in pediatric patients, it is necessary to study the information provided in the sections "Precautions" and "Method of application and dosage".
Contraindications
Hypersensitivity to any of the components of the drug. Hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics, children under 3 months of age.
FROM caution Imicinem-TF should be administered concomitantly with potentially nephrotoxic drugs, as well as in patients with dyspeptic symptoms, especially associated with colitis, and in elderly patients.
Precautionary measures
Use during pregnancy and lactation
Clinical safety of Imicinem-TF during pregnancy not installed. Therefore, Imicinem-TF should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. In each case, the drug must be used under the direct supervision of a physician.
If necessary, the use of Imicinem-TF during lactation consideration should be given to stopping breastfeeding.
special instructions
Imicinem-TF is not indicated for the treatment of meningitis because safety and efficacy have not been established. If meningitis is suspected, appropriate antibiotics should be given.
Patients on hemodialysis, especially with diseases of the central nervous system, Imicinem-TF can be prescribed only in cases where the expected benefit of therapy outweighs the potential risk of worsening renal failure.
During the treatment of infections caused by Pseudomonas aeruginosa, it is recommended to conduct periodic antibiotic sensitivity tests according to the clinical situation.
In order to prevent the development of resistance and maintain the effectiveness of Imicinem-TF, the medicinal product should only be used to treat or prevent infections caused by proven (or suspected) microorganisms susceptible to imipenem. In the absence of information on the identified pathogen and its susceptibility, the empirical choice of an antibiotic should be made on the basis of local epidemiological data and microbial susceptibility data.
Pediatric use
Imicinem-TF can be used to treat children with sepsis. The use of the drug in children under the age of 3 months, as well as in children with impaired renal function, has not been studied enough.
Method of application and dosage
The average daily dose of Imicinem-TF is determined depending on the severity of the infection and is divided into several equal doses, taking into account the degree of sensitivity of microorganisms, kidney function and body weight.
For adults the average therapeutic dose for intravenous infusion is 1-2 g / day (in terms of imipenem), divided into 3-4 infusions. The maximum daily dose is 4 g.
Table 1
Imicinem-TF at doses ≤500 mg should be administered intravenously over 20-30 minutes, at doses >500 mg - over 40-60 minutes. Patients who experience nausea during infusion should reduce the rate of administration.
For prevention of postoperative infections the drug should be administered intravenously at a dose of 1 g during induction anesthesia and at a dose of 1 g after 3 hours. In the case of high-risk surgery, an additional 500 mg should be administered 8 and 16 hours after anesthesia.
Doses of Imicinem-TF for IV infusion patients with dysfunctionkidney function andweighing 70 kg or more are presented in table 2.
Imicinem-TF should not be used in patients with creatinine clearance less than 5 ml/min/1.73 m2 unless hemodialysis is scheduled every 48 hours. Both imipenem and cilastatin are cleared from the circulation during hemodialysis. Imicinem-TF should be administered after a hemodialysis session and at 12-hour intervals from the end of the procedure.
table 2
| Daily dose based on the severity of the infection* | Recalculation of the daily dose depending on the QC (ml / min / 1.73 m2) | ||
| 41-70 | 21-40 | 6-20 | |
| 1 g | 250 mg every 8 hours or 250 mg every 12 hours | 250 mg every 12 hours | 250 mg every 12 hours | 250 mg every 12 hours |
| 1.5 ggg4 g | 250 mg every 6 hours 250 mg every 8 hours 500 mg every 8 hours 250 mg every 6 hours | 250 mg every 8 hours | 250 mg every 12 hours 250 mg every 12 hours |
| 2 g | 500 mg every 8 hours | 250 mg every 6 hours | 250 mg every 12 hours |
| 3 g | 500 mg every 6 hours | 500 mg every 8 hours | 500 mg every 12 hours |
| 4 g | 750 mg every 8 hours | 500 mg every 6 hours | 500 mg every 12 hours |
* see Table 1.
Children older than 3 months weighing less than 40 kg the drug is prescribed at a dose of 15-25 mg / kg / dose every 6 hours. Based on studies in adults, the maximum daily dose for the treatment of infections caused by fully susceptible microorganisms is 2.0 g per day, infections with moderate susceptibility of microorganisms (in primarily caused by some strains of P. aeruginosa) is 4.0 g/day. Higher doses (up to 90 mg/kg/day in older children) may be used in patients with cystic fibrosis. Medicine not recommended for use in children with CNS infections due to the risk of seizures and in children with body weight, as there are no data on the safety of use.
Rules for the preparation and administration of the solution
Imicinem-TF should be administered intravenously as an infusion.
To prepare a solution for in/inintroductions the contents of the vial are pre-dissolved in 10 ml of one of the following infusion solutions: 0.9% sodium chloride solution, 5%, 10% dextrose aqueous solution, 5% and 10% mannitol solution.
The resulting suspension must not be used for direct administration!
The suspension is shaken well and transferred into a vial or container with the rest of the infusion solution (140 ml). The total volume of the solution is 150 ml. To ensure complete transfer of the contents of the vial, the above procedure must be repeated by adding again 10 ml of the resulting solution to the vial, and after shaking, transfer to the vial or container with the rest of the solution. The resulting solution (150 ml) is shaken until a clear liquid is formed. To prepare a solutionImicinema-TFdo not use solvents containing lactic acid salt (lactate)!
Side effect
Local reactions: with a / in the introduction - erythema, pain and infiltrates at the injection site of the drug, thrombophlebitis.
Allergic reactions: rash, itching, urticaria, fever, anaphylactic reactions, erythema multiforme, angioedema; rarely - exfoliative dermatitis, toxic epidermal necrolysis.
Soaspects of the digestive system: nausea, vomiting, diarrhea; a moderate increase in the activity of transaminases, bilirubin and / or serum alkaline phosphatase, tooth staining; rarely - pseudomembranous colitis, hepatitis.
From the side of laboratory indicators: eosinophilia, leukopenia, neutropenia (including agranulocytosis), thrombocytopenia, thrombocytosis, decreased hemoglobin levels. In some cases, a direct positive Coombs test was noted.
From the sideurinarysystems: there was an increase in serum creatinine and urea nitrogen levels; rarely - oliguria / anuria, polyuria, acute renal failure. There have been cases of discoloration of urine (this phenomenon is safe and should not be confused with hematuria).
From the side of the central nervous system and peripheral nervous system: when prescribing intravenous infusions of Imicinem-TF (as well as in the treatment of other antibiotics of the beta-lactam group), cases of myoclonus, mental disorders, including hallucinations, confusion, epileptic seizures, paresthesia, and taste disturbances are described.
Side effects rarely require discontinuation of therapy and are usually mild and transient; severe side effects are rare.
Overdose
Symptoms: increased severity of side effects.
Treatment: the drug should be discontinued or its dose reduced. Carry out symptomatic therapy. It is possible to remove Imicinem-TF by hemodialysis, however, the effectiveness of this procedure in case of overdose has been little studied.
Interaction with other drugs
Pharmaceutical interaction
Imicinem-TF solutions should not be mixed or administered simultaneously with other antimicrobial drugs. Imicinem-TF is chemically incompatible with a lactic acid salt (lactate), therefore, when preparing drug solutions, solvents containing a lactic acid salt should not be used.
With simultaneous use with penicillins, cephalosporins and other beta-lactam antibiotics, cross-allergy is possible.
Terms and conditions of storage
Store in a place protected from moisture and light at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Shelf life 2 years. Do not use after the expiry date stated on the packaging.
Terms of dispensing from pharmacies
The drug is dispensed by prescription.
Package
250 mg/250 mg or 500 mg/500 mg in a 10 ml vial.
5 bottles in a pack or 36 bottles in a box (packaging for hospitals).
Manufacturing firm
JLLC "TripleFarm", st. Minskaya, 2B, 223141, Logoisk, Republic of Belarus, tel./fax: (+375) 1774 43 181, e-mail: .
