Impine Cilastatin: Instructions for use, caution and reviews. Dosage form with cilastatinia: Powder for the preparation of a solution for intramuscular administration of cilastatin instructions for use
Description
Powder from white to pale yellow color.
Composition on 1 bottle
dosage 250 mg / 250 mg
250 mg of imipenem / 250 mg of cilastatin and sodium bicarbonate
dosage 500 mg / 500 mg
500 mg of imipenem / 500 mg of cilastatin and sodium bicarbonate
Pharmacotherapeutic group
Antibiotic group of carbapenes.
ATH code: j01dh51.
Pharmacological properties
Pharmacodynamics
Imizine-TF is an antibiotic with a wide range of action consisting of two components.
The imipenem inhibits the synthesis of the cell wall of bacteria and has a bactericidal effect on wide spectrum Gram-positive and gram-negative pathogenic microorganisms, aerobic and anaerobic.
Sodium cilastatin inhibits dehydroppetidase - an enzyme metabolizing with an image in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cylastatin does not have its own antibacterial activity, does not oppress the bacteria beta-lactamase.
The antimicrobial spectrum of imizinem-TF includes actually all clinically significant pathogenic microorganisms. In vitro antibiotic active in relation to aerobic gram-negative bacteria: AChromobacter SPP., Acinetobacter SPP. (Earlier 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 strains that produce beta-lactamase), 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 producing penicillinase), Neisseria meningitidis, Pasteurella multocida, Proteus spp. (including Proteus Mirabilis, Proteus Vulgaris), Plesiomonas Shigelloides, Providencia SPP. (including Providencia Rettgeri / Previously 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 / earlier 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., Staphylococcus aureus (including strains producing penicillinase), Staphylococcus epidermidis (including strains producing penicillinase), Staphylococcus saprophyticus, Streptococcus spp. Groups in (including Streptococcus Agalactiae), Streptococcus SPP. Groups C, G, Streptococcus Pneumoniae, Streptococcus Pyogenes, Streptococcus Viridans (including hemolytic strains of alpha and gamma); 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 (formerly Bacteroides asaccharolytica), Prevotella bivia (formerly Bacteroides bivius) , Prevotella Disiens (Previously Bacteroides Disiens), Prevotella Intermedia (previously Bacteroides Intermedius), Prevotella Melaninogenica (Previously 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 imikin-TF sustainable Xanthomonas Maltophilia (previously Pseudomonas Maltophilia) and some Pseudomonas Cepacia strains, as well as Streptococcus Faecium and stable staphylococci stamps.
In vitro tests show that the antibiotic acts synergistically with antibiotics from the aminoglycoside group against some Pseudomonas Aeruginosa isolates.
Imicine-TF is effective as monotherapy or in combination with other antimicrobial means in the treatment of polyimicrobial infections.
Pharmacokinetics
Distribution
After in / in the introduction, the bioavailability of the imipenem is 98%. The antibiotic is well distributed, creating high concentrations in various tissues and body fluids. Binding with plasma proteins is 20%.
Metabolism and elimination
The imipenem is metabolized in the kidneys by hydrolysis of the beta-lactam ring under the action of kidney dehydropptidase. The half-life of the imipenem is 1 h.
Pharmacokinetics in special clinical cases
In violation kidney functionsAs well as in the elderly (over 65 years old) there is a decrease in total and renal clearance and an increase in the half-life of the imipenem.
Indications for application
Polyimicrobial and mixed aerobic-anaerobic infections, empirical therapy preceding the determination of pathogens microorganisms.
Infections caused by drug-sensitive strains of microorganisms: pneumonia (including intrabathic), infections of the urinary system, infections of the abdominal cavity, gynecological infections, infections of the skin and soft tissues, septicemia, bone and joint infection, infectious endocarditis, mixed infections.
Before using the drug in childhood patients, it is necessary to explore the information presented in the sections "Precautions" and "Method of Application and Dosage".
Contraindications
Increased sensitivity to any of the drug components. Hypersensitivity to carbapenes, penicillins or other beta-lactam antibiotics, children under 3 months.
WITH caution Imitation-TF should be prescribed simultaneously with potentially nephrotoxic drugs, as well as patients with dyspepsia symptoms, especially associated with colitis, and elderly patients.
Precautionary measures
Application in pregnancy and breastfeeding
Clinical Safety Imizinem TF during pregnancy not installed. Therefore, imicine-TF should not be applied during pregnancy, except in cases where the potential benefits of its use justifies possible risk For fetal. In each case, the drug must be applied under direct supervision of the doctor.
If necessary, the use of imizinem-TF during lactation Consideration should be considered about the cessation of breastfeeding.
Imicinee-TF is not shown for the treatment of meningitis, since security and efficacy have not been established. In suspected meningitis, it is necessary to assign appropriate antibiotics.
Patients in hemodialysis, especially with CNS diseases, imicine-TF can be prescribed only in cases where the intended benefit of therapy exceeds the potential risk of increased renal failure.
In the process of treating infections caused by a blue rod, it is recommended to conduct periodic tests for sensitivity to the antibiotic according to the clinical situation.
In order to prevent the development of resistance and maintenance of effectiveness, imicine-TF drug should be used only for the treatment or prevention of infections caused by proven (or presumably) sensitive microorganisms. If there is no information about the identified pathogel and its sensitivity, the empirical choice of antibiotics must be carried out on the basis of local epidemiological data and data on the sensitivity of microorganisms.
Use in pediatrics
Imicine-TF can be used to treat children with sepsis. The use of drug in children under the age of 3 months, as well as children with disorders of the kidney function, is not sufficiently studied.
Method of application and dosage
The average daily dose of imicinee-TF is determined depending on the severity of the infection and is distributed into several equal receptions, taking into account the degree of sensitivity of microorganisms, kidney functions and body weight.
For adults The average therapeutic dose with / in infusion is 1-2 g / day (in terms of the image), divided by 3-4 infusion. The maximum daily dose is 4 g.
Table 1
Imycinoma-TF in doses of ≤500 mg should be administered to / in for 20-30 minutes, in doses\u003e 500 mg - for 40-60 minutes. Patients who have nausea during infusion should reduce the rate of administration.
For prevention of postoperative infections The drug should be administered to / in a dose of 1 g at introductory anesthesia and at a dose of 1 g after 3 hours. in the case of surgical intervention with high degree Risk should be administered further than 500 mg after 8 and 16 hours after anesthesia.
Doses of imikinee-tf for in / in infusion patients with impaired functionkidney I.body weight 70 kg and more Presented in Table 2.
Imicine-TF should not be used in patients with creatinine clearance less than 5 ml / min / 1.73 m2, except when hemodialysis has been prescribed every 48 hours. As an impenet and cilastatin are derived from blood circulation during hemodialysis. Imicine-TF must be assigned after hemodialysis session and through 12-hour intervals from the moment the procedure is completed.
table 2
| Daily dose taking into account the severity of 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 in 8 h 250 mg after 12 hours | 250 mg after 12 hours | 250 mg in 12 hours | 250 mg in 12 hours |
| 1.5 GG4 G. | 250 mg after 6 h 250 mg after 8 h at 500 mg after 8 h 250 mg after 6 hours | 250 mg after 8 hours | 250 mg at 12 h 250 mg after 12 hours |
| 2 g | 500 mg after 8 hours | 250 mg after 6 hours | 250 mg in 12 hours |
| 3 g | 500 mg after 6 hours | 500 mg after 8 hours | 500 mg after 12 hours |
| 4 g | 750 mg after 8 hours | 500 mg after 6 hours | 500 mg after 12 hours |
* See Table 1.
Children over 3 months with body weight less than 40 kg The drug is prescribed at a dose of 15-25 mg / kg / dose every 6 hours. On the basis of research in adults, the maximum daily dose for the treatment of infections caused by fully sensitive microorganisms is 2.0 g per day, infections with moderate susceptibility of microorganisms (in The first of all caused by some strains R. Aeruginosa) is 4.0 g / day. Higher doses (up to 90 mg / kg / day, in older children) can be used in patients with cystic fibrosis. Medicine it is not recommended to apply in children with CNS infections Due to the risk of cramps and in children with body weight< 30 кг с нарушениями функции почек, Since there are no applications data.
Rules of preparation and introduction of the solution
Imycinoma-TF should be administered intravenously in the form of infusion.
For making a solution for in /at administration The contents of the vial are pre-dissolved in 10 ml of one of the following infusion solutions: 0.9% solution of sodium chloride, 5%, 10% aqueous solution of dextrose, 5% and 10% mannitol solution.
The resulting suspension cannot be used for direct introduction!
The suspension is well shaken and transferred to the bottle 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 bottle, the above procedure must be repeated, adding re-10 ml of the resulting solution to the bottle, and after shaking, transfer to the vial or container with the rest of the solution. The resulting solution (150 ml) shakes to form a transparent liquid. For making a solutionImicinema-TF. It is impossible to use solvents comprising a salt of lactic acid (lactat)!
Side effect
Local reactions: When in / in the introduction of erythema, pain and infiltrates at the injection site of the drug, thrombophlebitis.
Allergic reactions: rash, itching, urticaria, fever, anaphylactic reactions, multiform erythema, angioedema edema; Rarely - exfoliative dermatitis, toxic epidermal necroliz.
SOparties digestive system: nausea, vomiting, diarrhea; moderate increase in the activity of transaminases, bilirubin and / or serum alkaline phosphatase, dyeing of teeth; Rarely - pseudomambranous colitis, hepatitis.
From the laboratory indicators: Eosinophilia, leukopenia, neutropenia (including agranulocytosis), thrombocytopenia, thrombocytosis, reduction of hemoglobin levels. In some cases, a direct positive Cumbas test was noted.
From sideurinary Systems: An increase in serum creatinine and urea nitrogen levels were observed; Rarely - Oliguria / Anuria, polyuria, acute renal failure. There were cases of change in urine color (this phenomenon is safe, and it should not be confused with hematuria).
From the CNS and peripheral nervous system: When appropriated in / in infusion IMICOMEMA-TF (as in the treatment with other antibiotics of a group of beta-lactams), cases of myoclonia, mental disorders, including hallucinations, a confusion of consciousness, are described. epileptic seizures, Paresthesia, violations of taste.
Side effects rarely require termination of therapy and are usually moderate and passing; Heavy side effects It is rarely observed.
Overdose
Symptoms: Strengthening the severity of side effects.
Treatment: Drug should be canceled or reduced by a dose. Conduct symptomatic therapy. It is possible to remove imicinee-TF hemodialysis, but the effectiveness of this procedure under overdose is little studied.
Interaction with other medicines
Pharmaceutical interaction
Imicinema-TF solutions should not be mixed or administered simultaneously with other antimicrobial medicines. Imycinoma-TF is chemically incompatible with the milk acid salt (lactate), therefore, when preparing solutions of the drug, solvents containing a salt of lactic acid cannot be applied.
With simultaneous use with penicillins, cephalosporins and other beta-lactam antibiotics, cross allergies are possible.
Conditions and shelf life
Store in the place protected from moisture and light at a temperature not higher than 25 ° C.
Keep out of the reach of children.
Shelf life is 2 years. Do not use the expiration date specified on the package.
Conditions of vacation from pharmacies
The drug is discharged by a doctor's prescription.
Packaging
250 mg / 250 mg or 500 mg / 500 mg in a 10 ml bottle.
5 bottles in a bundle or 36 bottles in the box (packaging for hospitals).
Manufacturing firm
SOOO "Triplfarm", ul. Minskaya, 2B, 223141, Logoisk, Republic of Belarus, tel. / Fax: (+375) 1774 43 181, e-mail :.
Active substance
Impine, Tsilastatin
Dosage form
solution for infusion
Manufacturer
Jodas Expo, India
Structure
Active substances: The monohydrate imipenem (equivalent to anhydrous imperial) - 500 mg, cilastatin sodium salt (equivalent to cilastatin) - 500 mg;
auxiliary: Sodium carbonate anhydrous - 20 mg.
pharmachologic effect
Beta-lactam antibiotic of a wide range of action. Suppresses the synthesis of the cell wall of bacteria and has a bactericidal effect on a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic. The imipenem is a derivative of thionamicine, refers to the group of carbapenes. Sodium cilastatin inhibits dehydroppetidase - an enzyme metabolizing with an image in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract. Cylastatin does not have its own antibacterial activity, does not oppress the bacteria beta-lactamase. Active in relation Pseudomonas Aeruginosa, StareLococcus Aureus, Streptococcus Faecalis and Bacteroides Fragilis. Resistant to the destruction of bacterial beta lactamase, which makes it effective for many microorganisms, such as Pseudomonas Aeruginosa, Serratia SPP. and Enterobacter SPP., which are resistant to most beta-lactam antibiotics. The antibacterial spectrum includes almost all clinically significant pathogenic microorganisms. Active with respect to gram-negative aerobic bacteria: AChromobacter SPP., Acinetobacter SPP. (earlier 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, Gardnarella Vaginalis, Haemophilus Ducreyi, Haemophilus Influenzae (including strains forming beta lactamase) Haemophilus Parainfluenzae, Hafnia Alvei, Klebsiella SPP. (including Klebsiella Oxytoca, Klebsiella Ozaenae, Klebsiella Pneumoniae), Moraxella SPP., Morganella Morganii (earlier PROTEUS MORGANII), NEISSERIA GONORRHOEAE Neisseria Meningitidis, Yersinia SPP. (earlier Pasteurella) including Yersinia Multocida, Yersinia Enterocolitica, Yersinia Pseudotuberculosis; Plesiomonas Shigelloides, Proteus SPP. (including Proteus Mirabilis, Prodeus vulgaris), Providencia SPP. (including Providencia Alcalifaciens, Providencia Rettgeri (earlier 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 Marcescens, Serratia Proteamaculans), Shigella SPP.; Gram-positive aerobic bacteria: Bacillus SPP., Enterococcus Faecalis, Erysipelothrix Rhusiopathiae, Listeria Monocytogenes, Nocardia SPP., Pediococcus SPP., Staphylococcus aureus (including strains forming penicillinase) Staphylococcus Epidermidis.(including strains forming penicillinase) Staphylococcus Saprophyticus, Streptococcus Agalactiae, Streptococcus Pneumoniae, Streptococcus Pyogenes, Streptococcusgroup C, Streptococcus group G, green streptococci including alpha and gamma hemolytic strains); Gram-negative anaerobic bacteria: Bacteroides SPP.(including Bacteroides Distasonis, Bacteroides Fragilis, Prevotella Melaninogenica (earlier Bacteroides Melaninogenicus), Bacteroides Ovatus, Bacteroides Thetaiotaomicron, Bacteroides Uniformis, Bacteroides Vulgatus), Bilophila Wadsworthia, Fusobacterium SPP. including (Fusobacterium Necrophorum, Fusobacterium Nucleatum), Porphyromonas Asaccharolytica (earlier Bacteroides Asaccharialyticus), Prevotella Bivia (earlier Bacteroides Bivius), Prevotella Disiens (earlier Bacteroides Disiens), Prevotella Intermedia(earlier Bacteroides Intermedius), Veillonella SPP.; Gram-positive anaerobic bacteria: Actinomyces SPP., Bifidobacterium SPP., Clostridium SPP. (including Clostridium Perfringens), EUBACTER SPP., Lactobacillus SPP., Microaerophilic Streptococcus, Mobiluncus SPP., Peptococcus SPP., Peptostreptococcus SPP., PropioniBacterium SPP.(including PropioniBacterium Acne); Dr. Microorganisms: Mycobacterium Fortuitum, Mycobacterium Smegmatis.Some Staphylococcus SPP. (resistant to meticillin), Streptococcus SPP. (group D), Stenotrophomonas Maltophilia, Enterococcus Faeciumand some strains Pseudomonas Cepacia. Insensitive to imipere. Effective against many infections caused by bacteria, resistant to cephalosporins, aminoglycosides, penicillins. In vitro. Synergity acts with aminoglycosides against some strains Pseudomonas Aeruginosa.
Indications
Infectious inflammatory diseases caused by sensitive microorganisms (polyimicrobial or mixed aerobic anaerobic infections):
Infections of the lower departments respiratory tract;
Infection urinary tract;
Intraabdomominal infections;
Skin and soft tissue infections;
Infections of bones and joints;
Peritonitis;
Endocarditis;
Inflammatory diseases of the small pelvis organs.
Prevention postoperative complications.
Contraindications
Increased sensitivity to one of the components of the drug, as well as to other carbapenes, beta-lactam antibiotics, penicillins and cephalosporins;
Chronic renal failure at QC less than 5 ml / min / 1.73 m2 without hemodialysis;
Early childhood (up to 3 months);
In children - severe renal failure (serum creatinine concentration of more than 2 mg / dl).
Carefully
Diseases of the central nervous system (CNS), pseudomambranous colitis, patients with diseases of the gastrointestinal tract in history, with QC less than 70 ml / min / 1.73 m2, patients on hemodialysis, anticonvulsant therapy with valproic acid (reducing the effectiveness of therapy), elderly age.
Side effects
From the nervous system: myoclonia, mental violations, hallucinations, confusion of consciousness, epileptic seizures, paresthesia.
From the urinary system: Oliguria, Anuria, polyuria, acute renal failure (rarely).
From the digestive system: nausea, vomiting, diarrhea, pseudommbranous enterocolitis, hepatitis (rarely).
From the side of the blood formation and hemostasis system: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, reduction of HB, prothrombin time lengthening, positive Cumbac reaction.
Laboratory indicators: increasing the activity of "liver" transaminases and an osprey, hyperbilirubinemia, hyperoperinemia, an increase in urea nitrogen concentration; Direct positive Cumbs test.
Allergic reactions: skin rash, itching, urticaria, multiform exudative erythema (including Stevens-Johnson syndrome), angioedema edema, toxic epidermal necroliz (rarely), exfoliative dermatitis (rarely), fever, anaphylactic reactions.
Local reactions: skin hyperemia, painful infiltration at the injection site, thrombophlebitis.
Others: candidiasis, violation of taste.
Interaction
Pharmaceutically incompatible with salt of lactic acid, solutions of other antibiotics.
With simultaneous use with penicillins and cephalosporins, cross allergies are possible; Shows antagonism to other beta-lactam antibiotics (penicillins, cephalosporins and monobactamam).
With simultaneous use with Gancyclovir, the risk of generalized seizures increases. These drugs cannot be used simultaneously, with the exception of cases when potential advantages exceed a possible risk.
Drugs that block the channel secretion slightly increase the concentration in plasma and T1 / 2 of the imipenem (if high concentrations of the imipenem are required, these apply these medicinal products At the same time not recommended).
When using the drug, the serum concentration of valproic acid is reduced, which leads to a decrease in the effectiveness of anticonvulsant therapy, therefore, during the period of treatment it is recommended to monitor serum concentration Valproic acid.
How to accept, receive and dosage
In / in drip and in / m. The doses below are calculated on the body weight of 70 kg and more and KK 70 ml / min / 1.73 sq. M and more. For patients with CC, less than 70 ml / min / 1.73 sq. M and / or less body weight should be proportionally reduced by a dose. In / in the route of administration, it is preferable to use at the initial stages of therapy of bacterial sepsis, endocarditis, and others. Heavy and threatening life of infections, incl. infections of the lower respiratory tract caused by Pseudomonas Aeruginosa, And in the case of severe complications.
To prepare an infusion solution to the vial add 100 ml of solvent (0.9% NaCl solution, 5% aqueous solution of dextrose, 10% aqueous dextrose solution, solution of 5% dextrose and 0.9% NaCl, etc.). The concentration of the imipenem in the resulting solution is 5 mg / ml.
The average therapeutic dose for adults with in / in administration is 1-2 g / day, divided into 3-4 administration; The maximum daily dose is 4 g or 50 mg / kg, depending on which dose is less. Patients with a slight degree of gravity of infection - 250 mg 4 times a day, middle degree - 500 mg 3 times a day or 1 g 2 times a day, a severe degree - 500 mg 4 times a day, with infection that threatens the life of the patient - 1 g 3-4 times a day. Each 250-500 mg is introduced in / in for 20-30 minutes, and every 1 g - for 40-60 minutes.
For the prevention of postoperative infections - 1 g during introductory anesthesia and 1 g - after 3 hours. In the case of surgical interference with a high degree of risk of developing an infection (operation on the thick and rectum), 500 mg is additionally introduced after 8 and 16 hours after total anesthesia .
Maximum daily doses for in / in administration in patients with renal failure Depending on the severity of infection and QC values \u200b\u200b(ml / min / 1.73 sq. M):
with a light course of infection and QC 41-70 ml / min - 250 mg in 8 hours, KK 21-40 ml / min - 250 mg in 12 hours, KK 6-20 ml / min - 250 mg in 12 hours;
in the infection of moderate gravity and QC 41-70 ml / min - 250 mg after 6 h, KK 21-40 ml / min - 250 mg in 8 hours, KK 6-20 ml / min - 250 mg in 12 hours;
with severe flow (highly sensitive strains) and KK 41-70 ml / min - 500 mg in 8 hours, KK 21-40 ml / min - 250 mg in 6 hours, KK 6-20 ml / min - 250 mg through 12 h; With severe flow (moderately sensitive strains, incl. Pseudomonas Aeruginosa) and KK 41-70 ml / min - 500 mg after 6 h, KK 21-40 ml / min - 500 mg after 8 hours, KK 6-20 ml / min - 500 mg in 12 hours; With a severe course of infection, threatening life, and KK 41-70 ml / min - 750 mg after 8 hours, KK 21-40 ml / min - 500 mg in 6 hours, KK 6-20 ml / min - 500 mg after 12 hours
Patients with QC less than 5 ml / min are prescribed only if hemodialysis is carried out every 48 h, followed by introduction after 12 hours (from the moment of completion of the procedure).
For the prevention of postoperative infections in adults - 1 g at introductory anesthesia and re-after 3 hours; With surgical interventions with a high degree of risk (on the thick and rectum), another 500 mg is additionally introduced after an end of 8 and 16 hours after the start of general anesthesia. Currently, there is no sufficient data on the dosing regime in the preoperative prevention of patients with QC less than 70 ml / min / 1.73 sq.m.
Children with a mass of body 40 kg and more - the same doses as adults; with a body weight less than 40 kg - 15 mg / kg 4 times a day; Maximum daily dose - 2 g.
The introduction can be used as an alternative to / in the form of a drug for the treatment of infections, in which the introduction of preferable. Depending on the severity of infection, the sensitivity of pathogenic microorganisms and the state of the patient, 500-750 mg are introduced every 12 hours. The total daily dose is no more than 1,500 mg. If there is a need for large doses of the drug, it is necessary to use in / in the introduction.
Introduction Introduction in patients with QC less than 20 ml / min / 1.73 sq.m, and also did not have been studied in children.
For the treatment of urethritis and cervicitis caused by Neisseria Gonorrhoeae, Enter 500 mg once, in / m. The powder is mixed with 2 ml of 1% solution of hydrochloride lidocaine (without epinephrine), water for injection or 0.9% NaCl solution before the formation of a homogeneous suspension (white or light yellow color).
Overdose
Symptoms: It is possible to strengthen side effects.
Treatment symptomatic. The imipenem and cilastatin are hemodialysis. However, the effectiveness of this procedure in the overdose of the drug is unknown.
Special instructions
It is strongly required to comply with the recommended dosage and application scheme, especially in patients predisposed to convulsive activity. Therapy of anticonants in patients with epilepsy in history should continue the entire treatment period. If local tremor, myoclonium or convulsive seizures are observed, patients must undergo a neurological examination with the appointment of anticonvulsor therapy. The dosage of the drug in this case should be revised to determine whether it should be reduced or the drug must be canceled.
Dosage form Contains 37.56 mg (1.63 MEKV) sodium.
Before starting therapy, careful history of the previous allergic reactions to beta-lactam antibiotics should be collected. Under development allergic reaction The drug should be canceled immediately.
In the history of the disease gastrointestinal tract (especially colitis), there is an increased risk of the development of pseudomambranous colitis.
When applying the drug, both on the background of administration and after 2-3 weeks. After discontinuation of treatment, the development of diarrhea caused by Clostridium difficile (pseudomambranous colitis) is possible. In light cases, it is enough to cancel the treatment and use of ion exchange resins (kolistramin, a whisk), in severe cases, the compensation of fluid loss, electrolytes and protein, the purpose of vancomycin and metronidazole is shown. It is impossible to use drugs that brave intestinal peristalsis.
As in the case of other beta-lactam antibiotics, Pseudomonas Aeruginosa can quickly develop resistance to the drug during the treatment. Therefore, in the process of treating infections caused by Pseudomonas Aeruginosa, it is recommended to conduct periodic tests on the sensitivity to the antibiotic in accordance with the clinical situation.
Elderly patients are likely to have age disturbances of the kidney function, which may require a dose reduction.
On prescription
Barcode and weight
Barcode: 4602521011785
Weight: 0.027 kg;
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Dosage form: & nbsppowder for making a solution for infusion Structure:1 bottle / bottle:
Sterile mixture containing:
The monohydrate imipenem is 530.0 mg (in terms of imipenem - 500.0 mg), sodium cilastatin - 532.0 mg (in terms of cilastatin - 500.0 mg);ancillary: Sodium bicarbonate - 20.0 mg.
Description: B. something or white with yellowish tint powder. Pharmacotherapeutic Group:Antibiotic carbapenem + dehydroppetidase inhibitor ATH: & NBSPJ.01.d.h.51 Imipenem and inhibitor of dehydropptidase
Pharmacodynamics:The drug consists of two components:
1) imipenema, beta-lactam antibiotic a wide range of action, a thionampcin derivative related to the group of carbayenes;
2) cilastatin sodium - enzyme-inhibitor of metabolism imipenem in the kidneys and significantly increasing the concentration of unchanged imipenem in the urinary tract.
The simiphene suppresses the synthesis of the cell wall of bacteria and has a bactericidal effect on a wide range of gram-positive and gram-negative aerobic and anaerobic microorganisms.
Cylastine has no own antibacterial activity, does not oppress the bacteria beta lactamase.
The imipenem is resistant to the destruction of bacterial beta lactamase, which makes it effective for many microorganisms, such as Pseudomonas.aeruginosa., Serratia.sPP.. and Enterobacter.sPP. ., which are resistant to most beta-lactam antibiotics.
The antibacterial spectrum includes almost all clinically significant pathogenic microorganisms.
Active in the following microorganisms in vitro, as well as in vivo:
Gram-negative aerobic bacteria : A. cinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia spp., Incible Serratia marcescens;
Gram-positive aerobic bacteria
: Enterococcusfaecal.iS., Staphylococcus aureus. Staphylococcus Epidermidis. (including strains forming penicillinase) Streptococcus Agalactiae, Streptococcus Pneumoniae, Streptococcus Pyogenes;Gram-negative anaerobic bacteria : Bacteroides SPP., including Baeteroides Fragilis, Fusobacterium SPP;
Gram-positive anaerobic bacteria : Bifidobacterium SPP., Clostridium SPP., Eubaeterium SPP., Peptocoeecus SPP., Peplostreptococcus SPP., PropioniBacterium SPP.
The imipenem has a bactericidal effect of in vitro to the sedent microorganisms ( clinical efficacy is not installed):
Gram-positive aerobes : Bacillus SPP., Listeria Monocytogenes, Nocardia SPP., Staphylococcus saprophyticus, Streptococcusgroups C, G and group Viridans;
Gram-negative aerobasics : Aeromonas Hydrophila, Alcaligenes SPP., Capnocytophaga SPP., Haemophilus Ducreyi, Neisseria Gonorrhoeae, including strains forming penicillinase, Pasteurella SPP., Providencia Stuartii;
Gram-negative anaerobes : Prevotella Bivia, Prevotella Disiens, Prevotella Melaninogenica, Veillonella SPP.;
Insensitive : Enterococcus Faecium, methicillin resistantStaphylococcus SPP., Xanthomonas Maltophilia, Burkholderia Cepacia.
IN.vitro. synergity acts with aminoglycosides against some strains Pseudomonas.aeruginosa. .
Pharmacokinetics:After a / in the introduction of the solution of the drug, the time to achieve the maximum concentration (TC M AH) in the plasma is 20 minutes for both components. At the same time, the maximum concentration (with M ah) reaches values \u200b\u200bfrom 21 to 58 μg ml for the imipenem and from 21 to 55 μg / ml for cilastatin. After administration of the drug for 4-6 hours with M ah, the imipenem decreases to a value of 1 μg / ml and below.
The half-life for each of the components is 1 hour.
Plasma protein binding is 20% for imipenem and 40% - for cilastatin.
Approximately 7% introduced in / in the imipenem is excreted by the kidneys within 10 hours. The concentration of the imipenem in the urine over 10 μg / ml can be maintained for 8 hours after a / in the administration of the drug. About 70-80% of cilastatin is excreted by the kidneys within 10 hours after in the administration of the drug.
When in / in the introduction of the drug, a turn every 6 hours with a normal kidney function of the cumulation of imipenem / cilastatin in plasma or urine did not observe.
After in the administration of the drug at a dose of 1 g, the following averages of the concentration of the imipenem in the tissues and the human body environments were determined:
| Fabric or environment | Concentration of imipenem μg / ml or μg / g | Measurement time (h) |
| Intraocular fluid | ||
| Light fabric | ||
| Pleural liquid | ||
| Peritoneal fluid | ||
| Likvor (without inflammation) | ||
| Likvor (when inflammation) | ||
| Secret of the presenter | ||
| Tissue of prostate gland | ||
| Fallopiev pipes | ||
| Endometrium | ||
| Myometrium | ||
| Bone | ||
| Interstitial fluid | ||
The drug is used to treat severe infections caused by microorganism sensitive to it, as well as for empirical therapy of the infectious process even before determining its bacterial pathogens.
Intraabdominal infections caused by Enterococcusfaccalis, Staphylococcus.aureus. Staphylococcus epidermidis, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus spp., Pseudomonas aeruginosa, Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propioni bacterium SPP., Bacteroides SPP., including
Infections of the lower respiratory tract caused by Streptococcus Pneumoniae, Staphylococcus aureus (Penicillinase-producing strains), Acinetobacter SPP., Enterobacter SPP., Escherichia Coli, Haemophilus Influenzae, Haemophilus Parainfluenzae, Klebsiella SPP., Serratia Marcescens.
Urinary tract infections (complicated and uncomplicated) caused by Enterococcus Faecalis, Staphylococcus aureus(Penicillinase-producing strains), E nterobacter.sPP., Escherichia Coli, Klebsiella SPP., Morganella Morganii, Proteus Vulgaris, Providencia Rettgeri. Pseudomonas Aeruginosa.
Skin and soft tissue infections caused by Streptococcus Pyogenes, Enterococcus Faecalis, Staphylococcus aureus(Penicillinase-producing strains), Staphylococcus Epidermidis, Acinetobacter SPP., Citrobacter SPP., Enterobacter SPP., Escherichia Coli, Klebsiella SPP., Morganella Morganii, Proteus Vulgaris, Providencia Rettgeri, Pseudomonas Aeruginosa; Serratia SPP., Peptococcus SPP., PepTostReptococcus SPP., Bacteroides SPP., including B. Fragilis, Fusobacterium SPP.
Infections of bones and joints caused by Enterococcus Faecalis, Staphylococcus aureus(Penicillinase-producing strains), Staphylococcus Epidermidis, Enterobacter SPP., Pseudomonas Aeruginosa.
Bacterial septicemia caused by Streptococcus Pneumoniae, Enterococcus Faecalis, Staphylococcus aureus(Penicillinase-producing strains), Enterobacter SPP., Escherichia coli. Klebsiella SPP., Pseudomonas Aeruginosa, Serratia SPP., Bacteroides SPP., including Bacteroides Fragilis.
Infectious endocarditis. caused Staphylococcus aureus. (Penicillinasoproduction strains).
Gynecological infections caused by
Enterococcus Faecalis, Staphylococcus aureus(Penicillinase-producing strains).Staphylococcus Epider Midis, Streptococcus Agalactiae (Streptococcus SPP. Group B), Enterobacter SPP., Escherichia Coli, Gardnerella Vaginalis, Klebsiella SPP., Proteus SPP., Bifidobacterium SPP., Peptococcus SPP., Peptostreptococcus SPP., PropioniBacterium SPP., Bacteroides SPP., including V. Fragilis.Prevention of postoperative complications in risk group patients with a high probability of developing postoperative infection complications, as well as in patients with high risk of intraoperative infection during surgical intervention.
Contraindications:Increased sensitivity to any of the components of the drug; increased sensitivity To other carbapenes.
Heavy reactions of hypersensitivity (for example, anaphylactic reactions, severe skin reactions) to any other beta-lactam antibiotics (for example, penicillins or cephalosporins).
Children up to 3 months.
Children with impaired kidney function (serum creatinine more than 2 mg / dl).
Patients with creatinine clearance (QC) less than 5 ml / min / 1.73 m 2 (except in cases where hemodialysis will be carried out after 48 hours after infusion of the drug).
Carefully:Diseases of the central nervous system, with QC less than 70 ml / min 1.73 m 2, patients in hemodialysis, patients with diseases of the gastrointestinal tract in history, pseudomambranous colitis.
Pregnancy and lactation:Research in pregnant women was not conducted. The drug should be used during pregnancy only if the benefit of treatment justifies the potential risk to the fetus.
The imipenem is found in breast milk. If the use of the drug is recognized as necessary, then feeding a child breast milk should be stopped.
Method of use and dose:The dosage form for intravenous application should not be introduced intramuscularly.
The calculation of the total daily dose of the drug should be based on the severity of infection and distributed into several applications in equal doses, taking into account the degree of sensitivity of one or more pathogenic microorganisms, the functions of the kidneys and body weight.
Dosing diagram for adult patients with normal kidney function
The doses shown in Table 1 are calculated for patients with normal kidney function (creatinine clearance of more than 70 ml / min / 1.73 m 2) and body weight ≥70 kg.
In patients with creatinine clearance ≤70 ml / min / 1.73 m 2 (see table 2) and / or body weight less than 70 kg (see Table 3), a decrease in the dose of the drug is necessary. It is especially important to reduce the dose depending on the mass of the body in those patients whose mass is significantly lower than 70 kg, and or there is moderately pronounced or severe renal failure.
The average therapeutic daily dose is 1-2 g of imipenem, divided by 3-4 applications (see Table 1). For the treatment of medium severity infections, the drug can also be used at a dose of 1 g twice a day.
In the case of infections caused by less sensitive microorganisms, the daily dose of the drug for intravenous infusions can be increased to the maximum - 4 g (impements) per day or 50 mg / kg per day depending on which dose will be less.
Each dose of the drug for intravenous infusions, less than or equal to 500 mg should be administered intravenously for 20-30 minutes. Each dose of over 500 mg should be administered intravenously for 40-60 minutes.
Patients whom nausea appears during infusion should slow down the rate of administration of the drug.
Table 1. Dosing mode of the drug for intravenous infusion to adult patients with normal kidney function and body weight ≥70 kg *
| Severity of infection | Doseimipenem, mg. | Breakbetween infusions | Total daily dose |
| Heavy (sensitive pathogens) | |||
| Severe and or threatening life | |||
| Severe and or threatening life caused by less sensitive microorganisms (primarily some strains R. Aeruginosa.) |
* In patients with a body weight, less than 70 kg, a further proportional decrease in the administered doses is necessary.
Due to the high antimicrobial activity of the drug, it is recommended that its total daily dose does not exceed 50 mg of kg or 4 g (imipenem), depending on which dose is less.
Although patients with fibrosis with normal renal function were treated with a drug at a dose to 90 mg / kg per day, divided into several applications, the total dose did not exceed 4 g (imipenem) per day.
The drug was successfully used in monotherapy in oncological patients with weakened immunity in the case of confirmed or alleged infections, for example, sepsis.
Dosing diagram for adult patients with impaired kidney function
For the dose correction of the drug in the treatment of adult patients with impaired kidney function, it is necessary:
- Based on the characteristics of the infection, select the total daily dose of the drug from table 1.
- From Table 2, select the corresponding reduced dose of the drug, based on the daily dose (Table 1) and clearance of creatinine of this patient. (To calculate the time of infusion, see the section "Dosing Scheme for Adult Patients with Normal Kidney Function").
- From table 3 Select in the left column the body weight value nearest to the mass of the patient's body (kg).
Table 2. Dosing mode for intravenous infusion adult patients with impaired function kidneys and body weight ≥70 kg *
| Generaldaily dose of imipenem, from table 1 | |||
| 41-70 | 21-40 | 6-20 |
|
| 1.0 g per day | 250 mg after 8 hours | 250 mg after 12 hours | 250 mg after 8 hours |
| 1.5 g per day | 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours |
| 2.0 g per day | 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 12 hours |
| 3.0 g per day | 500 mg after 6 hours | 500 mg after 8 hours | 500 mg after 12 hours |
| 4.0 g per day | 750 mg after 8 hours | 500 mg after 6 hours | 500 mg after 12 hours |
* In patients with a body weight, less than 70 kg need a further proportional reduction in administered doses.
Table 3. Dosing mode for intravenous infusions to adult patients with impaired kidney and / or body weight less than 70 kg
Maximum daily dose 1.0 g
| Body mass (kg) | Clementine clearance (ml / min / 1.73 m 2) |
|||
| ≥71 kg | 41-70 | 21-40 | 6-20 |
|
| 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours | 250 mg after 12 hours |
|
| but 250 mg after 8 hours | 125 mg after 6 hours | 250 mg after 12 hours | 125 mg after 12 hours |
|
| 125 mg after 6 hours | 125 mg after 6 hours | 125 mg after 8 hours | 125 mg after 12 hours |
|
| 125 mg after 6 hours | 125 mg after 8 hours | 125 mg after 12 hours | 125 mg after 12 hours |
|
| 125 mg after 8 hours | 125 mg after 8 hours | 125 mg after 12 hours | 125 mg after 12 hours |
|
Maximum daily dose 1.5 g
| Body weight (kg) | Clementine clearance (ml / min / 1.73 m 2) |
|||
| \u003e 71 kg | 41-70 | 21-40 | 6-20 |
|
| 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours |
|
| 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 8 hours | 250 mg after 12 hours |
|
| 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours | 250 mg after 12 hours |
|
| 250 mg after 8 hours | 125 mg after 6 hours | 125 mg after 8 hours | 125 mg after 12 hours |
|
| 125 mg after 6 hours | 125 mg after 8 hours | 125 mg after 8 hours | 125 mg after 12 hours |
|
Maximum daily dose 2.0 g
| Body mass(kg) | Clement Creatininea (ml / min / 1.73 m 2) |
|||
| ≥71 kg | 41-70 | 21-40 | 6-20 |
|
| 500 mg after 6 hours | 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 12 hours |
|
| 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours |
|
| 250 mg after 6 hours | 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours |
|
| 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours | 250 mg after 12 hours |
|
| 250 mg after 8 hours | 125 mg after 6 hours | 125 mg after 8 hours | 125 mg after 12 hours |
|
Maximum daily dose 3.0 g
| Body weight (kg) | Clementine clearance (ml / min / 1.73 m 2) |
|||
| ≥71 kg | 41-70 | 21-40 | 6-20 |
|
| 1000 mg after 8 hours | 500 mg after 6 hours | 500 mg after 8 hours | 500 mg after 12 hours |
|
| 750 mg after 8 hours | 500 mg after 8 hours | 500 mg after 8 hours | 500 mg after 12 hours |
|
| 500 mg after 6 hours | 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 12 hours |
|
| 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours |
|
| 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 8 hours | 250 mg after 12 hours |
|
Maximum daily dose 4.0 g
| Body weight (kg) | Clementine clearance (ml / min / 1.73 m 2) |
|||
| ≥71 kg | 41-70 | 21-40 | 6-20 |
|
| 1000 mg after 6 hours | 750 mg after 8 hours | 500 m g after 6 hours | 500 mg after 12 hours |
|
| 1000 mg after 8 hours | 750 mg after 8 hours | 500 mg after 8 hours | 500 mg after 12 hours |
|
| 750 mg after 8 hours | 500 mg after 6 hours | 500 mg after 8 hours | 500 mg after 12 hours |
|
| 500 mg after 6 hours | 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 12 hours |
|
| 500 mg after 8 hours | 250 mg after 6 hours | 250 mg after 8 hours | 250 mg after 12 hours |
|
With the introduction of a dose of 500 mg to patients with creatinine clearance of 6-20 ml / min / 1.73 m 2, an increase in the risk of developing seizures is possible.
The preparation of the imipenem + cilastatin should not be administered intravenously to patients with creatinine clearance less than 5 ml / min / 1.73 m 2, except in cases where hemodialysis will be carried out no later than 48 hours after the infusion of the drug.
Hemodialysis
In the treatment of patients with creatinine clearance less than 5 ml / min / 1.73 m 2, which are in hemodialysis, recommendations should be applied on the dosing regime of the drug with an image + cyllastatin for patients with creatinine clearance 6-20 ml / min / 1.73 m 2 ( See "Dosing diagram for adult patients with a disturbed kidney function").
As an imipenem, gas and cilastatin are derived during hemodialysis from the circulatory system. In connection with the drug, the drug and cilastatin for intravenous infusions should be administered to patients after hemodialysis and then through 12 hour intervals from the moment the procedure is completed. Behind the patients on hemodialysis, especially if they have diseases of the central nervous system, careful observation should be carried out; The purpose of the drug with imipenem + cilastatin patients who are conducted by hemodialysis is recommended only in cases where the benefits of treatment exceeds the potential risk of developing seizures (see section "Caution").
Currently there are no sufficient data in order to recommend the drug with imipenem + cilastatin for intravenous administrations Patients located on peritoneal dialysis.
The state of the kidneys in elderly patients cannot be fully defined only on the basis of measuring the level of residual blood nitrogen or creatinine. To select dosages, such patients recommended the definition of creatinine clearance.
Elderly patients
For elderly patients with a normal kidney function, the dose correction is not required.
Violation of the liver function
For patients with a disturbed liver function, the dose correction is not required.
Prevention
Dosing mode for adult patients
For the prevention of postoperative infections in adults, the preparation of imipenem + cilastatin for intravenous infusions should be administered at a dose of 1 g at introductory anesthesia and then 1 g after 3 hours. In the case of surgical intervention with a high risk (for example, during operations on a thick and rectum), two additional doses of 500 mg in 8 and 16 hours after the introductory anesthesia should be administered.
Dosing diagram for children from 3 months of age
- Children with body weight ≥40 kg should receive the same doses as adult patients.
- Children over 3 months with a body weight of less than 40 kg should receive a drug at a dose of 15 mg / kg with 6-hour intervals. The maximum daily dose should not exceed 2
Preparation of solution for intravenous infusions
Preparation of imipenem + cilastatin for intravenous infusions can not be mixed or add to other antibiotics.
The drug shape of the drug with imipenem + cilastatin for intravenous infusions has a chemical incompatibility with lactic acid (lactate) and should not be prepared on the basis of solvents containing lactate. However, the intravenous drug is impened + cilastatin can be administered through the same infusion system as a solution containing lactate.
The solution of the drug with an image + cilastatin for intravenous infusions is prepared in accordance with the table below 4. The final infusion solution must be shaken until a transparent solution is obtained. The color of the solutions of the drug is impedite + cilastatin varies from colorless to yellow (color change within these limits does not affect the activity of the drug).
Table 4. Preparation of the solution of the drug with imipenem + cilastatin for intravenous infusion
| Dose of the drug with imipenem + cilastatin (mg of imipenem) | Volume of the solvent added (ml) | The average concentration of infusion solution of the drugImipenem + cilastatin (mg / ml imipenem) |
For a bottle of 20 ml, 25 ml
In the vial with the preparation with the image + cilastatin, it is pre-adding 10 ml of the corresponding solvent from the list presented in Table 5. The resulting primary suspension must be thoroughly shake and add to the infusion bottle containing 90 ml of an infusion solvent.
Primary suspension cannot be used for administration.
To complete the preparation of the drug, the procedure must be repeated. By adding a 10 ml of a previously obtained solution from the infusion bottle into the vial with the residues of the powder.
The resulting suspension must be thoroughly shake and add to the infusion bottle containing 90 ml of an infusion solvent. The total volume of the solvent is 100 ml.
The final infusion solution must be shaken until a transparent solution is obtained.
Table 5 presents data to the timing of the use of an infusion solution of the drug with imipenem + cilastatin. prepared on the basis of a number of infusional solvents and stored at room temperature or in the refrigerator.
Table 5.
| Solvent | The term of stability of the drug |
|
| Room temperature (25 ° С) | Fridge |
|
| 0.9% sodium chloride solution | ||
| 5% dextrose solution | ||
| 10% dextrose solution | ||
| 5% dextrose solution and 0.9 % sodium chloride solution | ||
| 5% Dextrose solution and 0.45% Sodium chloride solution | ||
| 5% dextrose solution and 0.225% sodium chloride solution | ||
| 5% Dextrose solution and 0.15% Potassium chloride solution | ||
| 5% and 10% Mennitol solution | ||
In clinical studies, impenet + [cilastatin] was administered intravenously 1723 patients. The most frequent systemic side effects probably associated with the use of the drug were nausea (2.0%), diarrhea (1.8%), vomiting (1.5%), rash (0.9%), fever (0.5 %), decrease in blood pressure (0.4%), convulsions (0.4%) (see section "Special instructions"), dizziness (0.3%), itch (0.3%), urticaria (0, 2%), drowsiness (0.2%).
The most frequent local side effects were flubite thrombophlebitis (3.1%), pain at the place of administration (0.7%), erythema at the place of administration (0.4%) and the scarring of the veins wall (0.2%). Also, it was often reported to increase the activity of serum transaminases and alkaline phosphatase.
Below are the side effects registered during clinical studies and in the post-registration experience of use.
Registered side effects are classified by frequency: very often (≥14 0), often (≥1 / 100,<110), нечасто (≥1/1000, <1/100), редко (≥1/10000, <1 1000), очень редко (< 1/10000), частота неизвестна.
Rarely: pseudomambranous colitis, candidiasis.
Very rarely: gastroenteritis.
From the blood and lymphatic system
Often: eosinophilia.
Infrequently: pancytopenia, neutropenia, leukopenia, thrombocytopenia, thrombocytosis.
Rarely: Agranulocytosis.
Very rarely: hemolytic anemia, oppression of the function of the red sprout of the bone marrow.
From the immune system
Rarely: anaphylactic reactions.
From the psyche
Infrequently: mental disorders, including hallucinations and confusion status of consciousness.
From the nervous system
Infrequently: cramps, myoclonia, dizziness, drowsiness.
Rarely: Encephalopathy, paresthesia, tremor, taste perversion.
Very rarely: the exacerbation of myasthenia, headache.
Frequency unknown:
Astemation, dyskinesia.From the hearing body and labyrinth disorders
Rarely: Reducing hearing.
Very rarely: Vertigo, ringing in the ears.
From heart
Very rarely: cyanosis, tachycardia, feeling of heartbeat.
From the vessels
Often: thrombophlebitis.
Infrequently: decrease in blood pressure.
Very rarely: "rings".
From the respiratory system, chest and mediastinal organs
Very rarely: shortness of breath, hyperventilation, sore throat.
From the gastrointestinal tract
Often: diarrhea, vomiting, nausea. Nausea and / or vomiting when using the drug with the image + [cilastatin], the cup was observed in patients with GPA nulocytopenia.
Rarely: Tooth coloring and or language.
Very rarely: hemorrhagic colitis, pain in the stomach, heartburn, glossitis, nourishpieces of language, hypersalization.
From the side of the liver and biliary tract
Seldom: Hepatic insufficiency, hepatitis.
Very rarely: fulminant hepatitis.
From the side of the skin and subcutaneous fabrics
Often: rash (including Exnttematous).
Infrequently: urticaria, itching.
Rarely: toxic epidermal necroliz, angioedema edema, Stevens-Johnson syndrome, multiform erythema, exfoliative dermatitis.
Very rarely: hyperhydrosis, changes in the structure of the skin.
From skeletal and muscular and connective tissue
Very rarely: Polyartralgia, pain in the thoracic spine.
From the kidneys and urinary tract
Rarely: acute renal failure, oliguria / anuria, polyuria, change in urine color (safe and should not be mistakenly taken for hematuria). The role of the drug with imipenem + cilastatin] in the changes in the renal function is difficult to assess, since other factors predispose to predenal azotemia or deterioration of the kidney function are usually present.
From the side of the genital organs and breast
Very rarely: genital itch.
General disorders and disorders at the injection site
Infrequently: fever, pain and sealing in the place of administration of the drug, erythema at the place of administration of the drug.
Very rarely: a sense of discomfort in the chest, asthenia / weakness.
Laboratory indicators
Often: increasing the activity of serum transaminases, an increase in alkaline phosphatase activity.
Infrequently: Positive direct Cumbac Test, an increase in prothrombin time, a reduction of hemoglobin, an increase in the concentration of serum bilirubin, an increase in the concentration of serum creatinine, an increase in blood urea nitrogen concentration.
Children (older 3-hover)
In a clinical study with the participation of 178 children over 3 months, the observed side effects were comparable to side effects registered in adult patients.
Overdose:Symptoms of overdose correspond to the profile of adverse reactions and may include convulsions, confusion, tremor, nausea, vomiting, reduction in blood pressure, bradycardia.
There is no special information on the treatment of overdose of the drug. Sodium is displayed during hemodialysis, but the effectiveness of this procedure in the overdose of the drug is unknown.
Interaction:The drug is pharmaceutically incompatible with lactic acid (lactate) and should not be prepared on the basis of solvents containing it. However, intravenously drug can be administered through the same infusion system as a solution containing lactate.
With simultaneous use with Gancyclovir, the risk of generalized seizures increases. These drugs cannot be used simultaneously, with the exception of cases when potential advantages exceed a possible risk.
Simultaneous use with probenecide is accompanied by a minimum increase in plasma concentration and half-life of the imipenem. In this connection, the simultaneous use of a probeclision and the drug is not recommended.
When using a drug with a valproic acid or sodium sofarmitoma, a plasma concentration of valproic acid is reduced. As a result of this interaction, the concentration of valproic acid may fall below the therapeutic level, which increases the risk of convulsion.
Although the interaction mechanism is unknown, data iN.vitro. and the results of animal studies suggest that carbapenes may inhibit hydrolysis, as a result of which glucuronid metabolite of valproic acid (VPA -G) is converted back to the valproic acid, which leads to a decrease in the concentration of the valprooic acid in the blood plasma (see "Special Instructions" section ).
The simultaneous use of antibacterial preparations with warfarin can enhance its anticoagulant effect. There are numerous reports of enhancing the anticoagulant effect of accepted oral anticoagulants, including, in patients simultaneously receiving antibacterial drugs.
The risk may vary depending on the infectious agent, age and the general state of the patient, therefore it is difficult to assess the influence of antibiotics to increase the international normalized relationship (many). It is recommended to periodically monitor the value of MNA during and immediately after the simultaneous use of antibacterial drugs with oral anticoagulants.
The drug should not be mixed in one syringe with other antibiotics, while allowed simultaneous - insulated - administration with other antibiotics (aminoglycosides).
Special instructions:Coloring urine in a reddish color (safe and should not be mistakenly taken for hematuria).
The dosage form for C / in administration should not be used for inside muscle administration.
There are data on partial cross allergies when applying the drug and other beta-lactam antibiotics - penicillins and cephalosporins. Before starting therapy, careful history of the previous allergic reactions to beta-lactam antibiotics should be collected. When developing an allergic reaction, the drug should be canceled immediately and take appropriate measures.
When applying a drug with a valproic acid or sodium sofarate, a plasma concentration of valproic acid is reduced, which leads to a decrease in the effectiveness of anticonvulsant therapy. An increase in the dose of valproic acid or sodium sofaat may be insufficient to overcome the effects of interaction. The simultaneous use of imipenem and valprooic acid / sodium sofedproat is not recommended. It should be given to the possibility of treatment of infections with antibacterial drugs of other groups (not carbapenes) in patients receiving anticonvulsant therapy with valproic acid or sodium sofarmatoma. If necessary, applying the drug may require additional anticonvulsant therapy.
With the use of almost all antibacterial drugs, the development of pseudomambranous colitis is possible, which in gravity can vary from lung to life-threatening. In connection with these patients, having a history of the gastrointestinal tract, in particular colitis, antibiotics should be prescribed with caution. It is important to consider the possibility of such a diagnosis as a pseudomambranous colitis, in patients entering diarrhea after applying antibacterial drugs. Although studies show that the main reason for the "colitis associated with antibiotics" is toxin produced by Clostridium.difficile Other possible reasons should be taken into account. In case of suspected or confirmation of the diagnosis of pseudommbranous colitis, it is necessary to consider the possibility of termination of therapy with the drug and conducting specific therapy. It is impossible to use drugs that brave intestinal peristalsis.
As in the case of other beta-lactam antibiotics, Rseudo Top.s.aeruginosa. It may quickly gain resistance to imipenem. Therefore, during the treatment, it is necessary to periodically determine sensitivity Pseudomonas Aeruginosa. To the antibiotic according to the clinical situation.
In order to prevent the development of resistance and maintenance of the effectiveness of the imipenem in clinical practice, the drug should be used only for the treatment of infections caused by proven (or presumably) microorganisms sensitive 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 athibition, and in the absence of such an empirical selection of the antibacterial drug is carried out on the basis of regional epidemiological data and sensitivity data.
As a result of the risk of developing hepatic toxicity (increasing the activity of "liver" transaminases, hepatic insufficiency, fulminant hepatitis) When applying the drug, the liver functions should be carefully monitored.
In patients with liver diseases, the condition of the liver function should be monitored during the use of the drug. Dose correction is not required.
As in the case of the use of other beta-lactam antibiotics, there were reports of adverse reactions from the central nervous system (CNS): myoclonia, confusion states of consciousness and convulsions, especially in cases where the doses recommended taking into account the functions of the kidneys and mass Body. Typically, such phenomena was observed in patients with damage to the central nervous system (brain injury or history of history) and / or in patients with a disturbed kidney function, in which the drug cumulation is possible. In this regard, especially in such patients, it is extremely necessary to strictly adhere to the recommended doses (see section "The method of application and dose").
Patients with convulsive disorders should continue anticonvulsant therapy.
In the event of tremor, myoclonium or convulsion, patients should be sent to a neurological examination and assign anticonvulsant therapy if it has not yet begun. If the symptoms from the CNS are persisted, then the dose of the drug should be reduced or canceled it.
The drug should not be used in patients with creatinine clearance ≤ 5 ml / min / 1.73 m 2 except in cases where hemodialysis will be carried out no later than 48 hours after the infusion of the drug. The use of the drug to patients who are conducted by hemodialysis is recommended only in cases where the benefits of treatment exceeds the potential risk of developing convulsion.
In children over 3 months, the drug is used according to the same indications as in adult patients.
Data on the efficiency and safety of the use of the cilastatine imipenem for in in administration in children up to 3 months and with a disturbed kidney function (serum creatinine more than 2 mg / dl) is not enough.
Dosage form contains 35.7 mg (1.55 meq) sodium.
Impact on the ability to control the transc. cf. And Meh.:Research on the effect of the drug on the ability to manage vehicles, mechanisms were not conducted. Some side effects associated with the use of the drug (for example, hallucinations, dizziness, drowsiness and vertigo) can affect the ability to control vehicles and work with mechanisms.
Release form / Dosage:Powder for preparing a solution for infusions, 500 mg + 500 mg.
Packaging:500 mg + 500 mg of active ingredients in vials from a glass tube for drugs with a capacity of 20 ml or 25 ml, hermetically sealed with rubber plugs, compressed aluminum caps or 500 mg + 500 mg of active ingredients in glass bottles for blood, infusion and transfusion drugs With a capacity of 100 ml, covered with corks rubber and compressed by aluminum caps.
1, 5 or 10 bottles with a capacity with a capacity of 20 ml or 25 ml are placed in individual packs of cardboard along with instructions for use.
1 The bottle with a preparation capacity of 100 ml is placed in an individual pack of cardboard along with instructions for use.
25 bottles with a capacity with a capacity of 20 ml or 25 ml with an application of instructions for use corresponding to the number of bottles, laid into a box of cardboard for consumer packaging (for hospitals).
35 bottles with a capacity of 100 ml are placed in cardboard boxes corrugated with an application of instructions for use corresponding to the amount of bottles (for hospitals).
Storage conditions:In the place protected from light, at a temperature not higher than 25 ° C.
Keep out of the reach of children.
Shelf life:3 years.
Do not use after the expiration date.
active substances:
1 vial contains an imipenem of a 530 mg monogeneration, which corresponds to 500 mg of the imipenem and sodium of cylastatin 530 mg, which corresponds to 500 mg of cilastatin;
auxiliary substances: sodium bicarbonate.
Dosage form
Powder for making a solution for infusions.
Basic physico-chemical properties: powder from white to almost white or slightly yellowish color.
Pharmacological group
Antibacterial agents for systemic use, carbapenes. The imipenem and enzyme inhibitor. Code ATX J01D H51.
Pharmacological properties
Pharmacological.
The imipenem / cilastatin-vista consists of two components: imipenem, the first representative of the new class B-lactam antibiotics - thienamicine, and cilastatin sodium, a special inhibitor of the enzyme, blocks the metabolism of the imipenem in the kidneys and significantly increases the concentration of unchanged imipenem in the urinary tract. The weight ratio of the imipenem and cilastatin sodium in the preparation is 1: 1.
The class of thienamicinic antibiotics, to which belongs to the image, is characterized by a wide range of powerful bactericidal action than the one that is provided by any of the led antibiotics.
The imipenem / cilastatin vista is shown for the treatment of mixed infections caused by the self-sensitive strains of aerobic and anaerobic bacteria. The imipenem / cilastatin vista discovered its effectiveness in the treatment of many infections caused by aerobic and anaerobic gram-positive and gram-negative bacteria, resistant to cephalosporins, including cefassoline, cefoperasone, cephalotine, cefoxitin, cefotaxim, moxalactam, cefathamandol, ceftazidim and ceftriaxone. A large number of infections due to resistant to aminoglycosides (gentamicin, amikacin, triamcin) and / or penicillins (ampicillin, carbenicillin, penicillin-G, ticarcillin, peperacillin, azelocillin, meslocylline) pathogens, also treating this combination.
The imipenem / cilastatin vista is not shown for the treatment of meningitis.
The imipenem / cilastatin vista is a powerful inhibitor of the synthesis of the cell wall of the bacterium and has a bactericidal effect on a wide range of gram-positive and gram-negative, aerobic and anaerobic pathogenic microorganisms.
The imipenem / cilastatin-vista together with the latest cephalosporins and penicillins has a wide range of action against gram-negative species, but its outstanding feature is high activity against gram-positive species, previously observed only in B-lactam antibiotics of the narrow spectrum.
The spectrum of activity of the drug image / cilastatin-vista covers Pseudomonas Aeruginosa, Staphylococcus Aureus, Enterococcus Faecalis and Bacteroides Fragilis, different in the composition and problematic in the clinical plan of pathogens, sustainable, as a rule, to other antibiotics.
The imipenem / cilastatin vista is effective against a large number of microorganisms, such as Pseudomonas Aeruginosa, types of Serratia and Enterobacter, which are from nature sustainable to most B-lactam antibiotics.
An antibacterial spectrum of imipenem / cilastatin is wider than any other known antibiotics, and covers all clinically important pathogenic microorganisms. To microorganisms, according to which the imipenem / cilastatin-vistazazvay, effective in vitro include:
Gram-negative aerobic bacteria
views of Achromobacter.
Views of Acinetobacter (formerly Mima-Herellea)
Aeromonas Hydrophila.
views of Alcaligenes
Bordetella Bronchicanis
Bordetella Bronchiseptica.
Bordetella pertussis
Brucella Melitensis
Burkholderia Pseudomallei (Previously Pseudomonas Pseudomallei)
Burkholderia Stutzeri (Previously Pseudomonas Stutzeri)
views Campylobacter
views of Capnocytophaga.
citrobacter species
Citrobacter Koseri (previously Citrobacter Diversus)
Citrobacter Freundii.
Eikenella Corrodens.
views Enterobacter
Enterobacter Aerogenes
Enterobacter Agglomerans.
Enterobacter Cloacae.
Escherichia Coli.
Gardnerella vaginalis.
Haemophilus Ducreyi.
Haemophilus influenzae (including strains producing b-lactamas)
Haemophilus Parainfluenzae.
types of klebsiella
Klebsiella oxytoca.
Klebsiella Ozaenae.
Klebsiella Pneumoniae.
views of Moraxella
Morganella Morganii (formerly Proteus Morganii)
NEISSERIA GONORRHOEAE (including strains producing penicillinase)
NEISSERIA MENINGITIDIS.
views Pasteurella
Pasteurella Multocida.
Plesiomonas shigelloides
views Proteus.
Proteus Mirabilis
Proteus vulgaris
views Providencia
Providencia alcalifaciens
Providencia Rettgeri (previously Proteus Rettgeri)
Providencia Stuartii.
Views Pseudomonas *
Pseudomonas Fluorescens.
Pseudomonas Putida.
Pseudomonas Aeruginosa.
salmonella types
Salmonella Typhi.
views of Serratia.
Serratia Proteamaculans (formerly Serratia Liquefaciens)
Serratia Marcescens.
types of shigella
Views of Yersinia (previously Pasteurella)
Yersinia Enterocolitica.
Yersinia pseudotuberculosis
* Stenotrophomonas Maltophilia (formerly Xanthomas Maltophilia, Previously, Pseudomonas Maltophilia) and the strains of Burkholderia Cepacia (previously Pseudomonas Cepacia) are generally insensitive about the preparation of imipenem / cilastatin-vista.
Gram-positive aerobic bacteria
views Bacillus.
Enterococcus Faecalis.
Erysipelothrix rhusiopathiae.
Listeria monocytogenes
views of Nocardia
pediococcus species
Staphylococcus aureus (including strains producing penicillinase)
Staphylococcus Epidermidis (including strains producing penicillinase)
Staphylococcus saprophyticus.
Streptococcus Agalactiae.
Streptococcus Group S.
Streptococcus Group G.
Streptococcus Pneumoniae.
Streptococcus pyogenes
Viridans Streptococci (including α and γ-hemolytic strains)
Enterococcus Faecium and some staphylococci-resistant staphyloclies, insensitive to the preparation of imipenem / cilastatin-vista.
Gram-negative anaerobic bacteria
views of Bacteroides.
Bacteroides Distasonis
Bacteroides Fragilis
Bacteroides Ovalus.
Bacteroides Thelaiotaomicron.
Bacteroides Uniformis
Bacteroides vulgatus.
Bilophila Wadsworthia.
types Fusobacterium
Fusobacterium Necrophorum
Fusobacterium nucleatum.
Porphyromonas Asaccharolytica (Previously Bacteroides Asaccharolyticus)
Prevotella Bivia (previously Bacteroides Bivius)
Prevotella Disiens (Previously Bacteroides Disiens)
Prevotella Intermedia (Previously Bacteroides Intermedius)
Prevotella Melaninogenica (Previously Bacteroides Melaninogenicus)
Gram-positive anaerobic bacteria
types of Actinomyces.
views Bifidobacterium
views Clostridium
Clostridium Perfringens.
views EUBACTERIUM.
views Lactoballus.
views Mobiluncus
Microaerophilic Streptococcus.
views of peptococcus
views of peptostreptococcus
Types of PropioniBacterium (including P. Acnes)
Mycobacterium Fortuitum
Mycobacterium Smegmatis.
In vitro tests indicate that the imipenem acts synergistically with aminoglycosides against some Pseudomonas Aeruginosa isolates.
Pharmacokinetics.
Imipenem. In healthy volunteers, the infusion of the drug / cilastatin-vista preparation in a dose of 500 mg for 20 minutes led to peak levels in the plasma of the imipenem from 21 to 58 μg / ml. The binding of the imipenem with human serum proteins is approximately 20%.
When applied separately, the impenet is metabolized in the kidneys of dehydropptidase-and. Individual recovery in the urine was in the range from 5 to 40%, on average in several studies - 15 - 20%.
Cilastatin is a specific dehydropeptidase-I enzyme inhibitor, it effectively suppresses the metabolism of the imipenem, therefore, the simultaneous use of imipenem and cilastatin allows you to achieve therapeutic antibacterial levels of imipenem in urine and plasma.
The half-life of the blood plasma imipenem was 1:00. Approximately 70% of the applied antibiotic was shown in intact form in the urine during 10:00, and the further removal of the drug was not observed. When using the preparation of imipenem / cilastatin-vista, according to the scheme, every 6:00 did not observe the accumulation of the imipelex in the plasma or urine in patients with normal kidney function. The combined use of the drug imipenem / cilastatin-vista samples led to a minimal increase in plasma levels and half-life of a blood plasma imipenem.
Cilastatin. Peak levels in the blood plasma of cilastatin after a 20-minute infusion of the drug at a dose of 500 mg were in the range of 21 to 55 μg / ml. Binding of cilastatin with human blood plasma proteins is approximately 40%. The half-life of cilastatin from blood plasma is approximately 1:00. Approximately 70 - 80% of the cylastatin dose The flow of 10:00 after the use of the drug is excreted unchanged with urine. After that, cilastatin was not detected in the urine. Approximately 10% were evident in the form of a N-acetyl metabolite, which has an inhibitory effect on the dehydropptidase, comparable to such a maternal preparation. The joint use of the drug and probelocide leads to an increase in the level of blood plasma and the half-life of cilastatin, but did not affect the recovery from the urine of cilastatin.
renal failure
After a single dose of imipenem / cilastatin 250 mg / 250 mg area under the concentration-time curve (AUC) for the imipenem increased, respectively, 1.1, 1.9 and 2.7 times in patients with insignificant (Creatinine clearance (CRCL 50 - 80 ml / min / 1.73 m 2), moderate (CRCl 30-80 ml / min / 1.73 m 2), and the area under the concentration-time curve (AUC) for cilastatin increased by 1.6, respectively, 2 and 6.2 times in patients with a minor, moderate and severe renal disadvantage compared to patients with normal kidney function.
After a single dose of imipenem / cilastatin 250 mg / 250 mg, used 24 hours after hemodialysis, the area under the concentration-time curve (AUC) for the imipenem and cilastatin was more respectively 3 7 and 16.4 times compared with patients with normal kidney function. Election with urine, renal clearance and clearance of imipenem and cilastatin decrease together with a decrease in the function of the kidneys after the introduction of the drug with imipenem / cilastatin-wist. The dose adjustment is necessary for patients with impaired kidney function.
liver failure
Pharmacokinetics of the imipenem in patients with hepatic insufficiency was established. - The limited volume of the hepatic metabolism of the imipenem is expected that hepatic insufficiency does not affect its pharmacokinetics. Therefore, no dose correction is recommended for patients with hepatic insufficiency.
The average clearance and o "The amount of distribution for the imipenem was about 45% higher in children (aged 3 months to 14 years) compared with adults. The area under the curve" Concentration - Time "(AUC) for the imipenem after the dose of imipenem / cylastatin 15/15 mg / kg body weight in children was about 30% higher than the exposure in adults receiving a dose of 500 mg / 500 mg. at a higher dose of exposure after use 25/25 mg / kg of imipenem / cilastane children was on 9% higher compared to exposure in adults received a dose of 1000 mg / 1000 mg.
Elderly patients
In healthy elderly volunteers (aged 65 to 75 years old with a normal kidney function for their age) pharmacokinetics of a single dose of imipenem / cylastatin 500 mg / 500 mg, which was introduced for 20 minutes, was coordinated with expected results in patients with minor renal failure For which any dose changes are considered unnecessary. The average semi-generation and cilastane of plasma from the plasma is respectively 91 ± 7 minutes and 69 ± 15 minutes. The multiple dosing had no effect on the pharmacokinetics of imipenem or cilastatin, and no accumulation of imipenem / cilastatin was observed.
Indications
Treatment of infections in adults and children older than 1 year caused by microorganisms sensitive to the drug:
- intra-abdominal infections;
- infectilation of the lower respiratory tract (heavy pneumonia, including hospital and fan, pneumonia)
- Intranatal and postpartum infections;
- complicated infections of the urogenital system;
- complicated skin and soft tissue infections;
- infections of bones and joints;
- septicemia,
- endocarditis.
The drug can be used in the treatment of patients with neutropenia, accompanied by fever, likely causes a bacterial infection.
Treatment of patients with bacteremia, which is associated or probably associated with any of the above infections.
Contraindications
Increased sensitivity to the components of the drug, other preparations of carbapenem, acute manifestations of increased sensitivity (for example, anaphylactic reactions, a severe skin reaction) to other ß-lactam antibiotics (for example, penicillin or cephalosporins).
Interaction with other medicines and other types of interactions
In patients receiving ganciclovir, together with imipenem / cilastato for intravenous application, generalized convulsions were noted.
These drugs can be applied together in the case when the expected benefit from application exceeds the possible risk.
It has been reported to reduce the level of valproic acid in the blood plasma while using carbapenes, and in some cases a sudden convulsions have been reported. Therefore, the simultaneous use of imipenem and valproic acid / sodium of the valproat is not recommended.
Oral anticoagulants.
The simultaneous use of antibiotics with warfarin can increase its anticoagulation effects. A lot of reports were obtained to increase the anticoagulant effects of oral anticoagulants, including warfarin, in patients who simultaneously take antibiotics. The risk may vary depending on the type of infection, age and the general status of the patient. It is recommended to carry out frequent monitoring of the international normalized ratio (INR) during and after the concomitant use of antibiotics with oral anticoagulants.
The simultaneous use of imipenema / cilastatin and probenacide led to a minimal increase in the concentration of the imipenem in the plasma and the half-life of the blood plasma imiphenema. The removal with the urine of the active (untapped) imipenem decreased to about 60% of the dose, when the drug was used with a probenecide. The simultaneous use of the drug and the probecide doubled the level of cilastatin in the plasma and the half-life of cilastatin, but there was no effect on the removal of cilastatin with urine.
Features of application
When choosing imipenem / cilastatin as a preparation for treatment in each particular case, the feasibility of using carbapenes, taking into account the gravity of infection, the prevalence of resistance to other suitable for the use of antibacterial agents and considering the possibility of the presence of bacteria resistant to the carbapine.
Hypersensitivity.
Some clinical and laboratory data are known, which indicate the partial cross-allergenity of the drug with imipenem / cilastatin-vista and other B-lactam antibiotics, penicillins and cephalosporins. Heavy reactions (including anaphylaxis) are observed when the majority of B-lactam antibiotics are applied. Before starting therapy, the drug should be carefully examined by the history of the patient for the presence of a reaction of hypersensitivity to carbapenes, penicillins, cephalosporins, other B-lactam antibiotics and other allergens (see the section "Contraindications").
If an allergic reaction developed during the use of the drug, the drug should be canceled and taken appropriate measures. Serious anaphylactic reactions require urgent therapy.
Liver functions.
During treatment with imipenem / cilastato, the liver functions should be carefully monitored due to the risk of hepatic toxicity (increasing transaminase level, hepatic insufficiency and lightning hepatitis).
Patients with previously existing liver disease should control the liver functions during treatment with imipenem / cilastato. No need for dose correction.
Hematology.
During treatment with imipenem / cilastato, a positive direct or indirect Cumbac sample is possible.
Antibacterial spectrum.
In front of any empirical treatment, an antibacterial spectrum of imipenem / cilastatin should be taken into account, especially under the states of the patient's threat. In addition, caution should be taken due to the limited sensitivity of certain pathogens (associated, for example, with bacterial infections of the skin and soft tissues) to imipenem / cilastatin. The use of imipenem / cilastatin is suitable for the treatment of these types of infections, if a specific pathogen has already been documented and known as sensitive or when there are very serious grounds to believe that the most likely pathogen (s) is susceptible (s) to such treatment. The simultaneous use of this means against the Staphylococcus Aureus-resistant Staphylococcus Aureus (MRSA) can be shown when the presence of MRSA infections is suspected or proven. The simultaneous use of aminoglycosides can be shown when Pseudomonas Aeruginosa infections are suspected or proven with approved indications.
Clostridium Difficile.
The development of pseudommabranous colitis was registered as a complication when applying almost all antibiotics; Its forms can be from the lungs to those who threaten the life of the patient. Therefore, antibiotics are necessary with caution to prescribe patients, in the history of which gastrointestinal diseases are provided, especially colitis. It is important to remember the possibility of developing pseudommabranous colitis, when the patient during treatment or after discontinuation of treatment with antibiotics develops diarrhea. It should be considered the possibility of termination of therapy with imipenem / cilastatin and the use of specific treatment of Clostridium difficile. Do not prescribe medicines that inhibit the peristaltics.
Renal failure.
In patients with impaired renal function, imipenem / cilastatin is cumulative. If the dose of the drug is not reduced due to the state of the kidney function, the development of adverse reactions on the part of the central nervous system is possible (see "Method of application and dose" and below).
Central nervous system (CNS).
As with the therapy with antibiotics of the group of β-lactam, when the preparation of the image / cilastatin-vista is used, side effects from the CNS, like myoclonium, confusion of consciousness or convulsions, especially in case of exceeding the recommended doses, which were determined depending on the function of the kidneys and body weight . Custom, such disorders were observed in patients with the damage to the central nervous system (brain injury or attacks of seizures in history) and / or in patients with impaired kidney function, in which the drug coupon is possible in the body. In this regard, especially for such patients, it is extremely necessary to strictly adhere to the recommended doses and therapeutic regime. Therapy with anticonvulsants need to continue patients with convulsions in history.
Especially closely should be treated with neurological symptoms or seizures in children with well-known risk factors for seizures or receiving concomitant treatment with drugs to reduce the intensity by the court.
If there are focal tremor, myoclonium or convulsive seizures in the treatment process, patients must undergo a neurological examination with the appointment of anticonvulsant therapy, if it has not been appointed. If the symptoms of disorders from the CNS are persisted, then the dose of the drug image / cilastatin-vista needs to be reduced or completely canceled the drug.
The imipenem / cilastatin vista is not shown to treat patients with creatinine clearance ≤ 5 ml / min / 1.73 m 2, except in cases where hemodialysis will be carried out after 48 hours. For patients with hemodialysis, imipenem / cilastatin-vista are recommended only when positive results of treatment exceed the potential risk of convulsion.
Excipients.
The drug contains 37.6 mg sodium (1.6 mg-eq.), What should be considered when using it to patients who are on a controlled sodium (volatile) diet.
Application during pregnancy or breastfeeding.
Pregnancy.
The use of the drug for the treatment of pregnant women is properly studied, so it is possible to assign it during pregnancy only if the expected benefit for pregnant women exceeds the potential risk to the fetus.
Breastfeeding period.
The imipenem and cilastatin are excreted in small quantities in breast milk. In case of the need to use the drug breastfeeding should be stopped.
The ability to influence the reaction rate when managing motor vehicles or other mechanisms.
Given the risk of side effects, such as hallucinations, drowsiness, dizziness, should avoid control of vehicles and working with mechanisms when using the drug.
Method of application and dose
The daose dose of the imipenem / cilastatin-vista is determined by taking into account the severity of infection, the type of the dedicated pathogen (s); It is distributed into several identical administration in equal doses, given the condition of the kidney function and body weight.
Adult patients with normal kidney function
Doses for patients with normal kidney function (creatinine clearance\u003e 70 ml / min / 1.73 m 2) and body weight of at least 70 kg:
- 500 mg / 500 mg every 6:00 or
- 1000 mg / 1000 mg every 8:00 or every 6:00.
For the treatment of infections, the species of bacteria (for example, Pseudomonas Aeruginosa), and severe infections (for example, in neutropenia of patients with fever) are recommended to use a dose of 1000 mg / 1000 mg every 6:00.
Dose should be reduced for patients with:
- KK ≤ 70 ml / min / 1.73 m 2 and / or
- with body weight less than 70 kg. Reducing the dose, depending on body weight, is especially important for patients with significantly less than 70 kg of body weight and / or moderate / severe renal function.
The dose for patients with body weight is less than 70 kg, is determined using the formula:
actual body weight (kg) * Standard dose
The maximum daily dose should not exceed 4000 mg / 4000 mg per day.
Adult patients with renal impairment
To determine the reduced dose for adult patients with impaired kidney function, it is necessary:
- Determine the total daily dose (i.e. 2000/2000, 3000/3000 or 4000/4000 mg), which is usually used to patients with normal kidney function.
- Choose the necessary mode of input of the reduced dose (see Table 1) according to the clearance of the creatinine of the patient and the duration of the infusion (see "Method of Application").
Table 1
Doses of imipenem / cilastatin for adult patients with impaired kidney functions and weighing ≥ 70 kg *
* For patients with a body weight, less than 70 kg dose should be proportionally reduced. Proportional to dose for patients with body weight
** When applying a dose of 500 mg / 500 mg to patients with creatinine clearance of 6-20 ml / min / 1.73 m 2 significantly increases the risk of convulsion.
Patients with clearance creatinine ≤ 5 ml / min / 1.73 m 2
The imipenem / cilastatin vista in for intravenous administration should not be appointed if they do not conduct hemodialysis over the next 48 hours.
hemodialysis
In the treatment of patients whose creatinine clearance ≤ 5 ml / min / 1.73 m 2 and hemodialysis are used, doses recommended by patients with creatinine clearance 6-20 ml / min / 1.73 m 2 (see Table 1 ).
Both the imipenem and cilastatin are derived during the hemodialysis. The patient must be introduced by imipenem / cilastatin immediately after the hemodialysis session and in the future to enter every 12:00 after its end. Patients in hemodialysis, especially those who have a major disease is the disease of the central nervous system, require careful observation; To prescribe with imipenem / cilastatin, this patients are recommended only under the condition that the expected effect exceeds the possible risk of convulsion (see "Features of application").
Today, there is not enough data regarding the use of the drug to patients on peritoneal dialysis, so it is not recommended to apply it to treat this category of patients.
liver failure
Dose adjustment is not required for patients with liver function disorders.
Elderly patients
Dose adjustment is not required for elderly patients with normal kidney function.
Children aged 1 year.
For the treatment of infections, the species of bacteria (for example, Pseudomonas aeruginosa), and severe infections (for example, in neutropenia of patients with fever), are recommended to use a dose of 25/25 mg / kg every 6:00.
Children under the age of 1 and / or with impaired kidney function.
Mode of application.
Each bottle is intended only for disposable.
Before applying the contents of the vial (powder), it is necessary to dissolve and dissolve accordingly (see
Recommendations below). Each dose not exceeding 500 mg / 500 mg of impenet / cilastatin-vista for intravenous use should be administered within 20-30 minutes. Each dose exceeding 500 mg / 500 mg should be administered for 40-60 minutes. If a patient appears nausea during infusion, it is necessary to reduce the rate of administration of the drug.
Preparation of the solution for intravenous administration.
The imipenem / cilastatin vista for infusion is produced in the form of a sterile powder in bottles containing 500 mg of the equivalent of the imipenem and 500 mg of equivalent of cilastatin.
The preparation of the image / cilastatin-vista as a buffer includes sodium bicarbonate, which provides a solution with a pH from 6.5 to 8.5. These pH changes do not have a significant difference if the solution is prepared and stored according to the above instructions. The preparation of impenet / cilastatin-vista for intravenous use contains 37.5 mg sodium (1.6 MEQ).
The sterile powder imipenem / cilastatin-vista should be dissociated as indicated in Table 2. The resulting solution must be shaken before the formation of a transparent liquid. The variability of the color of the solution from colorless to yellow does not affect the activity of the drug.
Table 2.
Preparation of the solution with imipenem / cilastatin vista for intravenous administration
The contents of the bottle must be suspended and bring to 100 ml by an appropriate solution for injection.
At the first stage, it is recommended to add about 10 ml of 0.9% sodium chloride solution into the vial. In exceptional cases, when a 0.9% sodium solution of chloride cannot be applied by clinical reasons, as a solvent can be used 5% glucose.
Shake well and transfer the suspension formed in a container with a solution for injection.
Warning: Suspension is not a ready-made solution for injections.
Repeat the procedure by adding 10 ml of the infusion solution again so that all the bottular contents move to the solution for infusion. The resulting mixture must be shaken until it becomes transparent.
The concentration of the reduced solution after the above procedure is approximately 5 mg / ml of imipenem and cilastatin.