Composition, form of production and packaging
Powder for the preparation of a solution for infusions of white or white with a yellowish hue of color.
1 f.
imipenem (in the form of monohydrate) 500 mg
cilastatin (in the form of cilastatin sodium) 500 mg
Excipients: sodium hydrogen carbonate 20 mg.
bottles (1) - packs of cardboard.
bottles (10) - cardboard boxes.
bottles (50) - cardboard boxes (for hospitals).
bottles (1-50) - cardboard boxes (for hospitals).
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
PHARMACHOLOGIC EFFECT
Imipenem is a broad-spectrum beta-lactam antibiotic, is a derivative of tienamycin and belongs to the carbapenem group. Suppresses the synthesis of the cell wall of bacteria 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, it does not inhibit beta-lactamase bacteria.
Imipenem + cilastatin is resistant to degradation 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:
Gram-positive aerobic bacteria: Enterococcus faecalis, Staphylococcus aureus (including strains forming penicillinase), Slaphylococcus epidermidis (including strains forming penicillinase). Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes;
Gram-negative aerobic bacteria: 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 Bacteroid fragilis, Fusobacterium spp.
Imipenem has a bactericidal effect in vitro on the following microorganisms:
Gram-positive aerobic bacteria: Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus saprophyticus, Streptococcus groups C, G and viridans;
Gram-negative aerobic bacteria: Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducreyi, Neisseria gonorrhoeae, including strains forming penicillinase, 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 acts synergistically with aminoglycosides against some strains of Pseudomonas aeruginosa.
PHARMACOKINETICS
The maximum concentration (C max ) of imipenem in intravenous (iv) administration in a dose of 250 mg, 500 mg, 1000 mg for 20 min is 14-24 Ојg / ml, 21-58 Ојg / ml, 41-83 Ојg / ml respectively. C max cilastatin with iv administration at a dose of 250 mg, 500 mg, 1000 mg for 20 minutes - 15-25 Ојg / ml, 31-49 Ојg / ml, 56-80 Ојg / ml, respectively. 20% of the administered dose of imipenem and 40% of cilastatin reversibly bind to blood plasma proteins.
Imipenem is distributed well and quickly in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids, reproductive organs. In low concentrations it is found in the cerebrospinal fluid (CSF). The volume of distribution in adults is 0,23-0,31 l / kg, in children 2-12 years - 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% for 10 hours) by glomerular filtration (2/3) and active tubular secretion (1/3): 1-2% is excreted through the intestine and 20-25% by the extranal route mechanism is unknown).
With IV introduction, the half-life period (T 1/2 ) of imipenem and cilastatin in adults is -1 hours, in children 2-12 years is 1-1.2 hours, in newborns T 1/2 imipenem is 1.7-7.4 hours , cilastatin -3,8-8,4 hours; if the renal function T 1/2 imipenem is violated - 2.9-4 hours cilastatin - 13.3-17.1 h.
Imipenem and cilastatin are rapidly and effectively (73-90%) excreted by hemodialysis (as a result of a 3-hour session of intermittent haemofiltration, 75% of the dose administered is removed).
INDICATIONS
Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:
- Lower respiratory tract infection;
- urinary tract infections;
- intra-abdominal infections;
- gynecological infections;
- bacterial septicemia;
- infections of bones and joints;
- skin and soft tissue infections;
bacterial endocarditis.
Prevention of postoperative infectious complications.
DOSING MODE
Intravenously drip.
The 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) is 1-2 g / day (calculated on imipenem) divided by 3-4 injections .
The maximum daily dose is 4 g or 50 mg / kg, depending on which dose is lower.
Depending on the severity of the infection, the following doses are recommended (calculation of doses for imipenem):
- with a mild course of infections and uncomplicated urinary tract infections - 250 mg 4 times a day (total daily dose of 1 g);
- in case of an average period of 500 mg 3 times a day or 1000 mg 2 times a day (total daily dose of 1.5-2 g);
- In severe and complicated urinary tract infections - 500 mg 4 times a day (total daily dose of 2 g);
- for an infection that threatens the patient's life - 1000 mg 3-4 times a day (total daily dose of 3-4 g).
For the prevention of postoperative infections - 1000 mg during the introductory anesthesia and 1000 mg - after 3 hours. In the case of surgical intervention with a high risk of infection (operation on the colon and rectum), additionally 500 mg are administered after 8 hours and 16 hours after the general anesthesia.
For patients with SC less than 70 ml / min / 1.73 m2 and / or body weight less than 70 kg , dose should be proportionally reduced (calculation of doses by imipenem):
The maximum daily dose of 1.0 g
Body weight, kg Creatinine clearance, ml / min / 1.73 m 2
? 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
The maximum daily dose of 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
The maximum daily dose of 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 h 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
The maximum daily dose of 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 5 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
The maximum daily dose of 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 minutes 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 SC less than 5 ml / min / 1.73 m 2, the drug is administered only if hemodialysis is performed no later than 48 h.
In patients with SC less than 5 ml / min / 1.73 m 2 , who are on hemodialysis, the drug should be given in doses recommended for patients with KK 6-20 ml / min / 1.73 m 2 , immediately after the hemodialysis session and through 12-hour intervals from the end of the procedure. Patients on hemodialysis, especially if they have CNS diseases, should be carefully monitored. The use of the drug in patients on hemodialysis is recommended only in those cases when the benefit from treatment exceeds the potential risk of seizures. At present, there is insufficient data to recommend the use of the drug for patients on peritoneal dialysis.
In children, starting at 3 months of age, with a body weight of 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 with a body weight of 40 kg or more are given the same doses as adults (see tables).
Preparation of a solution for infusion and administration
10 ml or 20 ml of a suitable solvent are added to the vial with the preparation. The vial is shaken well to obtain a uniform suspension.
The resulting suspension can not be used for administration!
The resulting suspension is transferred to a vial with the rest of the solvent (80-90 ml). The total volume of the solution is 100 ml. To completely transfer the drug (drug residues on the walls of the bottle), add 20 ml of the previously obtained solution to the bottle, shake well, then combine the two solutions. Thoroughly mix the resulting solution until it becomes clear. Only after this, the solution is ready for use. The community 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 preparation.
Enter intravenously drip.
The duration of the infusion depends on the chosen dose: 250-500 mg administered for 20-30 minutes; more than 500 mg - for 40-60 minutes. Patients who experience nausea during infusion should reduce the rate of administration of the drug.
Ready-made infusion solutions (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 stability times of drug solutions prepared on the basis of a number of infusion solutions.
The stability period of the drug solution
Storage at room temperature (25 В° C) Storage in refrigerator (4 В° C)
0.9% solution of sodium chloride 4 hours 24 hours
5% and 10% dextrose solution 4 hours 24 hours
5% dextrose solution with 0.9% sodium chloride 4 hours 24 hours
5% dextrose solution with 0.45% sodium chloride 4 hours 24 hours
5% dextrose solution with 0.225% sodium chloride 4 hours 24 hours
5% dextrose solution with 0.15% potassium chloride 4 hours 24 hours
5% and 10% mannitol solution 4 hours 24 hours
SIDE EFFECT
From the central nervous system: dizziness, drowsiness, myoclonia, mental disorders, hallucinations, confusion, convulsions, paresthesia, encephalopathy, tremor, headache, vertigo.
From the senses: loss of hearing, ringing in the ears, a violation of taste.
From the urinary system: oliguria, anuria, polyuria, acute renal failure, changes in the color of urine.
On the part of the digestive system: nausea, vomiting, diarrhea, pseudomembranous colitis, hemorrhagic colitis, hepatitis (including fulminant), hepatic insufficiency, jaundice, gastroenteritis, abdominal pain, glossitis, hypertrophy of the tongue papilla, staining of teeth or tongue, sore throat, hypersalivation , heartburn.
On the part of the respiratory system: a feeling of discomfort in the chest, shortness of breath, hyperventilation.
On the part of the organs of hematopoiesis: eosinophilia. leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, leukocytosis, basophilia, pancytopenia, oppression 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; reduction of hemoglobin and hematocrit, lengthening of prothrombin time; increased concentration of low density lipoproteins; hyponatriemnia, hyperkalemia, hypochloraemia; appearance of protein, erythrocytes, leukocytes, cylinders, increased concentration of bilirubin in the urine.
Allergic reactions: skin rash, itching, urticaria, erythema multiforme exudative, Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis, exfoliative dermatitis, fever, anaphylactic reactions.
From the cardiovascular system: lowering blood pressure, feeling palpitations, tachycardia.
Local reactions: skin hyperemia, painful infiltration at the injection site, phlebitis / thrombophlebitis.
Other: candidiasis, vaginal itching, cyanosis, hyperhidrosis, polyarthralgia, asthenia, burning behind the sternum, pain in the thoracic spine.
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 disease, with CC less than 70 ml / min / 1.73 m 2, patients on hemodialysis, anticonvulsant therapy with valproic acid (decreased effectiveness of therapy), elderly.
PREGNANCY AND LACTATION
Use during pregnancy is permissible only if the possible benefit of treatment for the mother exceeds the potential risk to the fetus.
Imipenem and cilastatin penetrate in small amounts in breast milk, therefore, the issue of stopping breastfeeding during treatment with the drug should be resolved.
APPLICATION FOR FUNCTIONS OF THE LIVER
contraindicated in chronic renal failure with QC less than 5 ml / min / 1.73 m 2 without hemodialysis
APPLICATION FOR CHILDREN
Contraindicated in early childhood (up to 3 months); in children - with severe renal failure (serum creatinine concentration more than 2 mg / dL)
APPLICATION IN ELDERLY PATIENTS
With caution should prescribe the drug to elderly patients
SPECIAL INSTRUCTIONS
Not recommended for the treatment of meningitis.
Strict adherence to the recommended dosage and schedule of use is strongly required, especially in patients predisposed to seizure activity. Therapy with anticonvulsant drugs in patients with epilepsy in history should last the entire period of treatment with the drug. If local tremor, myoclonia or convulsive seizures are observed, patients should undergo a neurologic examination with the appointment of anticonvulsant therapy. The dosage of the drug in this case should be reviewed to determine if it should be reduced or the drug should be canceled.
The dosage form contains 37.56 mg (1.63 meq) of sodium.
Before the start of therapy, a thorough anamnesis should be made about the previous allergic reactions to beta-lactam antibiotics. When developing an allergic reaction, the drug should be immediately discontinued.
People who have a history of GIT disease (especially colitis), there is an increased risk of developing pseudomembranous colitis.
When using the drug, both on the background of the introduction, and after 2-3 weeks. after discontinuation of treatment, the development of diarrhea caused by Clostridium difficile (pseudomembranous colitis) is possible. In mild cases, it is sufficient to cancel treatment and apply ion-exchange resins (colestyramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin and metronidazole. Do not use drugs that inhibit the intestinal motility.
As with other beta-lactam antibiotics, Pseudomonas aeruginosa can quickly develop resistance to the drug during treatment. Therefore, during the treatment of infections caused by Pseudomonas aeruginosa, it is recommended to conduct periodic tests for sensitivity to the antibiotic according to the clinical situation.
In elderly patients, the presence of age-related renal dysfunction is likely, which may require a dose reduction.
Stains urine in a reddish color.
Influence on ability to drive vehicles and work with mechanisms
Care should be taken when driving a car and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.
OVERDOSE
In case of an overdose, it is recommended to cancel the drug, the appointment of symptomatic and maintenance therapy. Imipenem is excreted by hemodialysis.
DRUG INTERACTION
Pharmaceutically incompatible with the salt of lactic acid, solutions of other antibiotics.
With simultaneous application with penicillins and cephalosporins, a 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 can not be used at the same time, except when the potential benefits exceed the possible risk.
Drugs that block tubular secretion, slightly increase the concentration in the plasma and T 1/2 imipenem (if high concentrations of imipenem are required, it is not recommended to use these medicines 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 it is recommended to monitor the serum concentration of valproic acid during the treatment period.
TERMS OF RELEASE FROM PHARMACY
They lower the prescription.
TERMS AND CONDITIONS OF STORAGE
In the dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life. 2 years.
