Тиенам®
Producer: Merck Sharp & Dohme Corp. (Merck Sharp and Doum of the Building) USA
Code of automatic telephone exchange: J01DH51
Release form: Firm dosage forms. The powder lyophilized for preparation of solution for infusions.
General characteristics. Structure:
Active ingredients: 500 mg of an imipenem of sterile, 500 mg of a tselastin of sodium sterile.
Excipients: Natrii hydrocarbonas is sterile.
The combined antibiotic of a broad spectrum of activity.
Pharmacological properties:
Pharmacodynamics. The antibiotic of a broad spectrum of activity consisting of two components: 1) an imipenema, the first representative of a new class beta лактамных antibiotics - tiyenamitsin; and 2) a tsilastatina of sodium - the specific enzyme-inhibitor which is slowing down metabolism of an imipenem in kidneys and considerably not changed imipenem increasing concentration in urinary tract.
Тиенам® inhibits synthesis of a cell wall of bacteria and has bactericidal effect concerning a wide range of gram-positive and gram-negative pathogenic microorganisms, aerobic and anaerobic.
Tiyenam's resistance to splitting, including the penicillinases produced by gram-positive and gram-negative bacteria and tsefalosporinaza, provides with bacterial β-lactamelements its efficiency. Feature of drug consists in preservation of high activity concerning groups of gram-positive aerobic cocci, insensitive to other antibiotics (Staphylococcus aureus, Streptococcus faecalis), gram-negative Pseudomonas aeruginosa, Serratia spp., Enterobacter spp. and others steady against action of the majority beta лактамных antibiotics, and also anaerobe bacterias (Bacteroides fragilis).
Тиенам® in vitro, and also according to clinical trials of in vivo is active at in introduction at patients with various infectious diseases concerning gram-positive aerobic bacteria: Enterococcus faecalis (imipeny in vitro concerning Enterococcus faecium is inactive), Staphylococcus aureus, including the strains producing a penicillinase, Staphylococcus epidermidis, including the strains producing a penicillinase (Methicillinum - resistant staphylococcus are steady against imipeny), Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes; gram-negative aerobic bacteria: Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa (imipeny in vitro concerning Xanthomonas (Pseudomonas) maltophilia and some strains of P. cepacia is not active), Serratia spp., including S. marcescens; gram-positive anaerobic bacteria: Bifidobacterium spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp.; gram-negative anaerobic bacteria: Bacteroides spp., including B. fragilis, Fusobacterium spp.
Imipenem is active in vitro at values of the minimum overwhelming concentration (MOC) of 4 mkg/ml and less concerning the majority (≥90%) of the following strains of microorganisms; however clinical safety and efficiency of an imipenem at introduction in oil in treatment of the infections caused by these microorganisms was not confirmed in clinical trials.
Gram-positive aerobic bacteria: Bacillus spp., Listeria monocytogenes, Nocardia spp., Staphylococcus prophyticus, Streptococcus of group C, Streptococcus of group G, Streptococcus viridans; gram-negative aerobic bacteria: Aeromonas hydrophila, Alcaligenes spp., Capnocytophaga spp., Haemophilus ducreyi, Neisseria gonorrhoeae, including the strains producing a penicillinase, Pasteurella spp., Providencia stuartii; gram-negative anaerobic bacteria: Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Veillonella spp.
In vitro tests testify to a synergism at interaction of an imipenem and antibiotics of group of aminoglycosides concerning some clinical strains of Pseudomonas aeruginosa
Linkng with proteins of plasma of an imipenem makes 20%, a tsilastatin - 40%.
Later in/in Tiyenam's introductions in a dose of 1 g the following average values of concentration of an imipenem (definition was carried out in 1 h after introduction) in the following tissues and environments of a human body were defined:
At in Tiyenam's introduction to volunteers with normal function of kidneys in each 6 h cumulation of an imipenema/tsilastatin in plasma or urine did not observe.
Removal. T1/2 for each of components makes 1 h. About 70% entered into an imipenem are removed by kidneys during 10 h. Concentration of an antibiotic in urine more than 10 mkg/ml can remain for 8 h later in/in Tiyenam's introductions. About 70% of a tsilastatin are removed by kidneys during 10 h later in/in administrations of drug (500 mg of an imipenem of +500 mg of a tsilastatin).
Pharmacokinetics in special clinical cases. At healthy volunteers of advanced age (65-75 years with normal age function of kidneys) pharmacokinetic parameters in 20 min. after single in/in introductions of 500 mg of an imipenem and 500 mg of a tsilastatin corresponded to parameters at persons with a renal failure of easy degree.
Тиенам® it is intensively brought out of an organism by means of the procedure of a hemodialysis, however expediency of holding this procedure in case of drug overdose is not established now.
Indications to use:
Treatment of the heavy infections caused by sensitive microorganisms and also for empirical therapy of infectious process before definition of bacterial activators:
— the lower respiratory tract infections caused by Streptococcus pneumoniae, Staphylococcus aureus (the strains producing a penicillinase), Acinetobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp., Serratia marcescens;
— infections of the urinary tract (complicated and uncomplicated), the caused Enterococcus faecalis, Staphylococcus aureus (the strains producing a penicillinase), Enterobacter spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa;
— the intraabdominal infections caused by Enterococcus faecalis, Staphylococcus aureus (the strains producing a penicillinase), 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., Propionibacterium spp., Bacteroides spp., including B.fragilis, Fusobacterium spp.;
— the gynecologic infections caused by Enterococcus faecalis; Staphylococcus aureus (the strains producing a penicillinase), Staphylococcus epidermidis, Escherichia coli; Streptococcus agalactiae (group B streptococci), Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Klebsiella spp., Proteus spp., Bifidobacterium spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp., Bacteroides spp., including B.fragilis;
— the bacterial septicaemia caused by Streptococcus pneumoniae, Enterococcus faecalis; Staphylococcus aureus (the strains producing a penicillinase), Enterobacter spp., Escherichia coli, Klebsiella spp, Serratia spp., Bacteroides spp., including B.fragilis, Pseudomonas aeruginosa;
— the infections of bones and joints caused by Enterococcus faecalis; Staphylococcus aureus (the strains producing a penicillinase), Staphylococcus epidermidis, Enterobacter spp., Pseudomonas aeruginosa;
— the infections of skin and soft tissues caused by Streptococcus pyogenes, Enterococcus faecalis; Staphylococcus aureus (the strains producing a penicillinase), 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.;
— the infectious endocarditis caused by Staphylococcus aureus (the strains producing a penicillinase).
For prevention of postoperative infections at patients of risk group with high probability of development of a postoperative infectious complication, and also at patients with high risk of intraoperative infection during surgical intervention.
Route of administration and doses:
Тиенам® enter in/in in the form of infusion. Drug is not intended for introduction in oil. The recommended doses of the drug Tiyenam® are given at the rate on imipeny. Calculation of the general daily dose of Tiyenam is made taking into account severity of an infection, degree of sensitivity of one or several pathogenic microorganisms, function of kidneys and body weight. The daily dose is distributed on several infusions in equal doses.
For the purpose of treatment by the adult with normal function of kidneys (KK more than 70 ml/min. / 1.73 sq.m) and body weight ≥ 70 kg administer the drug in the doses given in table 1.
The average therapeutic daily dose makes 1-2 g, divided into 3-4 introductions to days (table 1). For treatment of moderately severe infections it is also possible to use drug on 1 g 2 times/days.
In case of the infections caused by less sensitive microorganisms the daily dose of drug for in/in infusions can be increased to maximum - 4 g/days or 50 mg/kg/days depending on what dose will be less.
Тиенам® in a single dose of 500 mg or less it is necessary to enter in/in in the form of infusion within 20-30 min. The drug in a single dose more than 500 mg should be administered in/in in the form of infusion within 40-60 min. If during infusion there is nausea, then it is necessary to slow down drug rate of administering.
Table 1. The mode of dosing of Tiyenam for in/in infusions at adults with normal function of kidneys and body weight ≥ 70 kg.
* At patients with body weight less than 70 kg are necessary a further proportional dose decline.
Due to the high antibacterial activity of Tiyenam it is recommended that his general daily dose did not exceed 50 mg/kg or 4 g/days. However patients with a mucoviscidosis with normal function of kidneys received Tiyenam® in the dose to 90 mg/kg/days divided into several receptions, at the same time the general dose did not exceed 4 g/days.
Тиенам® it was successfully applied as monotherapy at oncological patients with the weakened immunity in case of the confirmed or estimated infections, for example sepsis.
Adults with a renal failure. At patients with KK ≤ 70 ml/min. / 1.73 sq.m (table 2) and/or with a body weight less than 70 kg (table 3) the drug dose decline is necessary. The dose decline depending on body weight at those patients who have a weight much below 70 kg is especially important, and/or there is a renal failure of average or heavy degree.
At treatment of adult patients with an impaired renal function it is necessary for dose adjustment of drug:
— based on characteristics of an infection to choose the general daily dose of drug from table 1;
— to choose the corresponding reduced drug dose from table 2, proceeding from a daily dose (table 1) and KK at this patient. Infusions time according to the dosing mode for adult patients with normal function of kidneys.
Table 2. The mode of dosing of Tiyenam for in/in infusions by the adult with a renal failure and body weight ≥ 70 kg.
* At patients with body weight less than 70 kg are necessary a further proportional dose decline.
Table 3. The mode of dosing of Tiyenam for in/in infusions by the adult with body weight less than 70 kg. Maximum daily dose of 1 g.
Maximum daily dose of 1,5 g.
Maximum daily dose of 2 g.
Maximum daily dose of 3 g.
Maximum daily dose of 4 g.
At administration of drug in a dose in 500 mg at patients with KK of 6-20 ml/min. / 1.73 sq.m increase in risk of development of spasms is possible.
Тиенам® it is not necessary to apply at patients with KK less than 5 ml/min. / 1.73 sq.m unless not later than in 48 h after Tiyenam's infusion the hemodialysis is carried out.
Hemodialysis. At treatment of patients with KK less than 5 ml/min. / 1.73 the sq.m which are on a hemodialysis it is necessary to apply recommendations about the mode of dosing of Tiyenam for patients with KK of 6-20 ml/min. / 1.73 sq.m (as it is stated above).
As imipeny, and циластатин are brought during a hemodialysis out of the blood circulatory system. In this regard Tiyenam® should be entered after a hemodialysis and then the bucketed 12 h from the moment of completion of the procedure. It is necessary to provide careful observation of the patients who are on a hemodialysis, especially with TsNS diseases. Tiyenam's appointment is only recommended to the patients who are on a hemodialysis when the expected advantage of therapy exceeds potential risk of development of spasms.
Now there are not enough data to recommend Tiyenam® for treatment of the patients who are on peritoneal dialysis.
At patients of advanced age the condition of kidneys cannot be fully estimated only on the basis of determination of level of residual nitrogen of blood or creatinine. For selection of a dose at this category of patients definition of KK is recommended.
For the purpose of prevention of postoperative infections of Tiyenam® enter the adult in a dose 1 g at introduction anesthesia and then 1 g in 3 h. In case of surgical intervention with a high risk (for example, at operations on thick and a rectum) it is necessary to enter 2 additional doses on 500 mg in 8 and 16 h after an introduction anesthesia.
Children at the age of 3 months are also more senior. To children with body weight ≥ 40 kg appoint drug in the same doses, as well as the adult.
To children 3 months with body weight <40 kg drug are more senior it is necessary to appoint 15 bucketed mg/kg of 6 h in a dose.
The maximum daily dose - 2 g.
Rules of preparation of solution for infusions. Tiyenam's solution for infusions cannot be mixed or added to other antibiotics.
The dosage form of Tiyenam for infusions has chemical incompatibility with lactic acid (lactate) therefore for preparation of infusion solution the solvents containing a lactate are not used. However Tiyenam's solution for infusions can be entered through the same infusional system, as the solution containing a lactate.
Tiyenam's solution for infusions is prepared according to the recommendations presented in table 4. The received solution needs to be stirred up before formation of transparent liquid. Solution okrashennost options from yellow to colourless do not influence activity of drug.
Table 4. Preparation of solution of Tiyenam for infusions.
Contents of a bottle of 20 ml need to be dissolved previously in 10 ml of the corresponding solvent. The received solution cannot be used for introduction. This solution is well stirred up, and then transferred to a bottle or a container with other part of solvent (90 ml). The total amount of solvent – 100 ml.
For full dissolution of drug: add 10 ml of the solution received earlier to a bottle of 20 ml. The received solution is well stirred up, then both received solution combine. Carefully mix the received solution. The total amount of solvent – 100 ml.
Table 5. Terms of use of solution of Tiyenam for infusions prepared on the basis of a number of infusion solutions and stored at the room temperature or in the refrigerator.
Features of use:
Imipenem is found in breast milk in the person. In need of use of drug in the period of a lactation breastfeeding should be stopped.
The average therapeutic daily dose makes 1-2 g, divided into 3-4 introductions to days (table 1). For treatment of moderately severe infections it is also possible to use drug on 1 g 2 times/days.
In case of the infections caused by less sensitive microorganisms the daily dose of drug for in/in infusions can be increased to maximum - 4 g/days or 50 mg/kg/days depending on what dose will be less.
Тиенам® in a single dose of 500 mg or less it is necessary to enter in/in in the form of infusion within 20-30 min. The drug in a single dose more than 500 mg should be administered in/in in the form of infusion within 40-60 min. If during infusion there is nausea, then it is necessary to slow down drug rate of administering.
Table 1. The mode of dosing of Tiyenam for in/in infusions at adults with normal function of kidneys and body weight ≥ 70 kg.
* At patients with body weight less than 70 kg are necessary a further proportional dose decline.
Due to the high antibacterial activity of Tiyenam it is recommended that his general daily dose did not exceed 50 mg/kg or 4 g/days. However patients with a mucoviscidosis with normal function of kidneys received Tiyenam® in the dose to 90 mg/kg/days divided into several receptions, at the same time the general dose did not exceed 4 g/days.
Тиенам® it was successfully applied as monotherapy at oncological patients with the weakened immunity in case of the confirmed or estimated infections, for example sepsis.
Adults with a renal failure. At patients with KK ≤ 70 ml/min. / 1.73 sq.m (table 2) and/or with a body weight less than 70 kg (table 3) the drug dose decline is necessary. The dose decline depending on body weight at those patients who have a weight much below 70 kg is especially important, and/or there is a renal failure of average or heavy degree.
At treatment of adult patients with an impaired renal function it is necessary for dose adjustment of drug:
— based on characteristics of an infection to choose the general daily dose of drug from table 1;
— to choose the corresponding reduced drug dose from table 2, proceeding from a daily dose (table 1) and KK at this patient. Infusions time according to the dosing mode for adult patients with normal function of kidneys.
Table 2. The mode of dosing of Tiyenam for in/in infusions by the adult with a renal failure and body weight ≥ 70 kg.
* At patients with body weight less than 70 kg are necessary a further proportional dose decline.
Table 3. The mode of dosing of Tiyenam for in/in infusions by the adult with body weight less than 70 kg. Maximum daily dose of 1 g.
Maximum daily dose of 1.5 g.
Maximum daily dose of 2 g.
Maximum daily dose of 3 g.
Maximum daily dose of 4 g.
At administration of drug in a dose in 500 mg at patients with KK of 6-20 ml/min. / 1.73 sq.m increase in risk of development of spasms is possible.
Тиенам® it is not necessary to apply at patients with KK less than 5 ml/min. / 1.73 sq.m unless not later than in 48 h after Tiyenam's infusion the hemodialysis is carried out.
Hemodialysis. At treatment of patients with KK less than 5 ml/min. / 1.73 the sq.m which are on a hemodialysis it is necessary to apply recommendations about the mode of dosing of Tiyenam for patients with KK of 6-20 ml/min. / 1.73 sq.m (as it is stated above).
As imipeny, and циластатин are brought during a hemodialysis out of the blood circulatory system. In this regard Tiyenam® should be entered after a hemodialysis and then the bucketed 12 h from the moment of completion of the procedure. It is necessary to provide careful observation of the patients who are on a hemodialysis, especially with TsNS diseases. Tiyenam's appointment is only recommended to the patients who are on a hemodialysis when the expected advantage of therapy exceeds potential risk of development of spasms.
Now there are not enough data to recommend Tiyenam® for treatment of the patients who are on peritoneal dialysis.
To children with body weight ≥ 40 kg appoint drug in the same doses, as well as the adult.
To children 3 months with body weight <40 kg drug are more senior it is necessary to appoint 15 bucketed mg/kg of 6 h in a dose. The maximum daily dose - 2 g.
Тиенам® enter in a look in/in infusions therefore it is more preferable to apply it at the initial stages of treatment of bacterial sepsis, endocarditis and other heavy or life-threatening infections, including the lower respiratory tract infections caused by Pseudomonas aeruginosa and in case of considerable physiological disturbances, for example, of shock.
Against the background of treatment by Tiyenam development of the life-threatening states requiring special attention of medical staff and a possibility of rendering emergency medical service is possible. The anaphylaxis, spasms and severe clinical forms of pseudomembranous colitis caused by Clostridium difficile belong to such states.
As well as in a case with others beta лактамными antibiotics, Pseudomonas aeruginosa can develop quickly enough resistance to Tiyenam in the course of treatment. Therefore in the course of treatment of the infections caused by Pseudomonas aeruginosa it is recommended to carry out periodic sensitivity tests to an antibiotic in compliance with a clinical situation.
For the purpose of prevention of development of resistance and maintenance of efficiency of Tiyenam in clinical practice drug should be used only for treatment of the infections caused it is proved (or presumably) sensitive to imipeny by microorganisms. In the presence of information on the identified activator and its sensitivity to antibiotics the doctor is guided by it for the choice of an optimum antibiotic, and in the absence of that the empirical choice of antibacterial drug is carried out on the basis of local epidemiological data and data on sensitivity.
There are data on a partial cross allergy at Tiyenam's use and others beta лактамных antibiotics - penicillin and cephalosporins. For the majority beta лактамных antibiotics it was reported about a possibility of development at their use of heavy reactions (including an anaphylaxis). Development of Clostridium difficile-associated of diarrhea is caused by the aggressive growth of population of C.difficile in the conditions of suppression of normal flora in a large intestine with accumulation of the toxins A and B produced by a microorganism. The strains capable to hyperproduction of toxins, cause the most hard cases, refractory to any antibacterial therapy and sometimes the demanding colectomies. Therefore at emergence at the patient of diarrhea against the background of treatment by Tiyenam it is necessary to exclude first of all the C.difficile-associated etiology, considering described in clinical practice late (in 2 months after completion of antibacterial therapy) cases of development of this complication. In case of suspicion/confirmation of the C.difficile-associated diarrhea, perhaps, Tiyenam's cancellation with co-administration of therapy for maintenance of water and electrolytic balance, parameters of protein metabolism, suppression of an infection of C.difficile, and also consultation of the surgeon will be required.
It is necessary to consider that the dosage form of Tiyenam of 500 mg for infusions contains 37.5 mg of sodium (1.6 мэкв).
According to clinical trials efficiency and Tiyenam's safety at in introduction at patients of advanced age are more senior than 65 years does not differ from those at persons of younger age. However, considering disturbances of functions of cardiovascular system, a liver, kidneys, characteristic of this age group, and also existence of associated diseases and the accompanying medicamentous therapy, care at the choice of a dose is required. For this category of patients it is necessary to adhere to the lower bound of the recommended doses. It is reasonable to carry out monitoring of secretory function of kidneys.
Use in pediatrics. At children 3 months are more senior drug is used according to the same indications, as at adult patients.
For in/in infusions children aged up to 3 months and with a renal failure (serumal creatinine more than 2 mg/dl) have not enough data on efficiency and safety of use of Tiyenam.
Side effects:
Тиенам® it is usually well transferred. During clinical trials Tiyenam's portability was same as portability of cefazolin, cefalotin and tsefatoksim. Side effects, as a rule, do not demand the termination of therapy and usually are poorly expressed and passing. Heavy side effects meet seldom.
Side effects of Tiyenam which are noted most often are listed below.
From the alimentary system: nausea, vomiting, diarrhea. Risk of development of the pseudomembranous colitis caused by Clostridium difficile (as well as in case of use of other antibacterial drugs of a broad spectrum of activity) both in time, and after completion of treatment. Hemorrhagic colitis, hepatitis (including fulminantny), a liver failure, jaundice, a gastroenteritis, a glossitis, a hypertrophy of nipples of language, an abdominal pain, pigmentation of teeth and language, heartburn, hypersalivation, increase in serumal transaminases, bilirubin and/or ShchF are possible.
From TsNS: encephalopathy, a tremor, confusion of consciousness, a myoclonia, paresthesias, вертиго, a headache, mental disorders, including hallucinations.
From sense bodys: decrease in hearing, a ring in ears, a food faddism.
From respiratory system: feeling of discomfort in a breast, short wind, a hyperventilation, pain in chest department of a backbone.
From cardiovascular system: heartbeat, tachycardia.
Allergic reactions: rash, itch, urticaria, hyperhidrosis, cyanosis, Stephens-Johnson's syndrome, Quincke's disease, toxic epidermal necrolysis (seldom), exfoliative dermatitis (seldom), mnogoformny erythema, fever, including and medicinal, anaphylactic reactions.
From electrolytic balance: decrease in serumal concentration of sodium and chlorine, increase in potassium concentration.
From an urinary system: an oliguria/anury, a polyuria, a proteinuria, an erythrocyturia, a leukocyturia and a cylindruria, increase in concentration of bilirubin and discoloration of urine (safely it should also not be mistakenly accepted for a hamaturia). Increase in serumal concentration of urea and creatinine, acute renal failure (seldom). It is difficult to estimate Tiyenam's role in changes of renal function as usually there are also other factors contributing to a prerenalny azotemia or deterioration in function of kidneys.
Change of laboratory indicators: pancytopenia, oppression of function of a red sprout of marrow, thrombocytopenia, leukopenia, neutropenia, hemolitic anemia, eosinophilia, leukocytosis, thrombocytosis, monocytosis, lymphocytosis, increase in quantity of basophiles, decrease in level of hemoglobin and hematocrit, agranulocytosis, increase in a prothrombin time. At some patients the positive direct test of Koombs can be noted. Against the background of a granulocytopenia noted more frequent episodes of nausea and vomiting during treatment by Tiyenam.
Local reactions: phlebitis/thrombophlebitis, pain, an erythema, consolidations of a vein, infection in a drug injection site.
Others: pharyngalgia, candidiasis, increase maintenance of LPNP.
Interaction with other medicines:
At the patients receiving at the same time ганцикловир and Tiyenam® in the form of infusions generalized spasms were observed. It is not necessary to appoint these drugs at the same time unless potential advantages exceed possible risk.
Simultaneous introduction with probenetsidy is followed by the minimum increase in plasma concentration and Tiyenam's T1/2 therefore use of a probenetsid during treatment by an antibiotic is not recommended.
At Tiyenam's introduction there is a reduction of concentration of valproic acid in a blood plasma that is followed by risk of increase in convulsive activity (the cases registered in clinical practice) therefore during treatment by Tiyenam monitoring of concentration of valproic acid in a blood plasma is recommended.
Тиенам® it is not necessary to mix in one syringe with other antibiotics, at the same time the simultaneous isolated introduction with other antibiotics (aminoglycosides) is authorized.
Contraindications:
— patients with KK <5 ml/min. / 1.73 sq.m;
— children's age up to 3 months;
— children with a renal failure (serumal creatinine more than 2 mg/dl);
— hypersensitivity to drug components;
— hypersensitivity to others beta лактамным to antibiotics, penicillin and cephalosporins.
With care it is necessary to use drug at patients with pseudomembranous colitis, gastrointestinal diseases in the anamnesis, at KK <70 ml/min. / 1.73 sq.m, at the patients who are on a hemodialysis at TsNS diseases.
Overdose:
In case of Tiyenam's overdose drug withdrawal, purpose of a symptomatic and maintenance therapy is recommended. There is no special information on treatment of overdose of Tiyenam.
Imipenem and циластатин sodium are removed when carrying out a hemodialysis, however efficiency of this procedure at overdose of drug is unknown.
Storage conditions:
Drug should be stored in the place, unavailable to children, at a temperature not above 25 °C. A period of validity - 2 years.
Issue conditions:
According to the recipe
Packaging:
Bottles glass with a capacity of 20 ml (10) - pallets plastic.
Bottles glass with a capacity of 20 ml (25) - packs cardboard.
Bottles glass with a capacity of 115 ml (5) complete with connecting tubes (5 pieces) - boxes cardboard.
