Инванз®

General characteristics. Structure:

Active ingredient: 1,213 g of an ertapenem of sodium that corresponds to the maintenance of an ertapenem of 1 g.

Excipients: sodium bicarbonate, sodium hydroxide - to рН. Content of sodium makes about 137 mg (6 мЭкв).

Pharmacological properties:

Pharmacodynamics. The antibiotic from group of karbapenem, represents 1-β-метил-карбапенем, beta лактамный the antibiotic of long action for parenteral administration having activity against a wide range of gram-positive and gram-negative aerobic and anaerobic bacteria.

Bactericidal activity of an ertapenem is caused by inhibition of synthesis of a cell wall and mediated by its binding about the penicillin-the connecting proteins (PCP). At Escherichia coli he shows strong affinity to PSB 1a, 1b, 2, 3, 4 and 5, and it is preferable - to PSB 2 and 3. Ertapenem has considerable resistance to action β-лактамаз the majority of classes (including penicillinases, tsefalosporinaza and β-lactamelements of an expanded range, but not металло-β-лактамазы).

Инванз® it is effective against the majority of strains of the following microorganisms of in vitro and at the infections caused by them.

It is active concerning aerobic and optional anaerobic gram-positive microorganisms: Staphylococcus aureus (including the strains producing a penicillinase; Methicillinum - resistant staphylococcus are steady), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.

Many strains of Enterococcus faecalis and the majority of strains of Enterococcus faecium are steady.

It is active concerning aerobic and optional anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including the strains producing β-lactamazu), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis.

It is active concerning anaerobic microorganisms: Bacteroides fragilis and other Bacteroides spp., sort Clostridium microorganisms (except Clostridium difficile), microorganisms of the sort Eubacterium, microorganisms of the sort Peptostreptococcus, Porphyromonas asaccharolytica, sort Prevotella microorganisms.

The data on sizes of the minimum overwhelming concentration (MOC) given below are received in the researches in vitro, however their clinical importance is unknown.

Инванз® at MPK of ≤1 mkg/ml it is active against the majority (≥90%) of strains of microorganisms of the sort Streptococcus, including Streptococcus pneumoniae; at MPK of ≥0.5 mkg/ml - against the majority (≥90%) of strains of microorganisms of the sort Haemophilus; at concentration of ≤2 mkg/ml - against the majority (≥90%) of strains of other aerobic and optional anaerobic microorganisms; at concentration of ≤4 mkg/ml - against the majority (≥90%) of strains of anaerobic microorganisms of the list given below. However safety and efficiency of the drug Invanz® at treatment of the infections caused by these microorganisms in clinical practice was not confirmed in high-quality and well controlled clinical trials.

It is active concerning aerobic and optional anaerobic gram-positive microorganisms: sort Staphylococcus microorganisms, koagulazonegativny, sensitive to Methicillinum (Methicillinum - resistant staphylococcus are steady), Streptococcus pneumoniae (penicillin - resistant), Streptococcus viridans.

Many strains of Enterococcus faecalis and the majority of strains of Enterococcus faecium are steady.

It is active also concerning aerobic and optional anaerobic gram-negative microorganisms: Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli (producing β-lactamelements of an expanded action spectrum), Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae (producing β-lactamelements of an expanded action spectrum), Morganella morgani, Proteus vulgaris, Serratia marcescens.

Many strains of the listed above microorganisms having multiresistance to other antibiotics, for example, to penicillin, cephalosporins (including the III generations) and to aminoglycosides, are sensitive to the drug Invanz®.

It is active concerning anaerobic microorganisms of the sort Fusobacterium.

The defined MPK values have to be interpreted according to the criteria specified in table 1.

Table 1. Criteria of sensitivity for an ertapenem.

a Lack of data on resistant strains does not give now the chance to define any category differently as "sensitive". If according to research MPK strains are characterized not as sensitive, they have to be sent to laboratory for a further research.

b Streptococcus pneumoniae sensitive to penicillin (diameter of a zone of 1 mkg of an oksatsillinovy disk of ≥20 mm) can be considered sensitive to ertapeny. Isolates with a diameter of zone of 1 mkg of oksatsillinovy disk of ≤19 mm have to be tested for sensitivity to ertapeny by method of definition of MPK.

c Streptococcus pneumoniae Isolates sensitive to penicillin (MPK of ≤0.06 mkg/ml), and Streptococcus spp. (except S. pneumoniae), sensitive to penicillin (MPK ≤ 0.12 mkg/ml), can be considered sensitive to ertapeny. Testing of isolates with intermediate sensitivity to penicillin or penicillin - resistant isolates on sensitivity to ertapeny is not recommended as reliable criteria of interpretation for an ertapenem are absent.

d Beta and hemolitic Streptococcus spp., sensitive to penicillin (diameter of a zone of 10 PIECES of a penicillinic disk of ≥24 mm) can be considered sensitive to ertapeny. Isolates with a diameter of zone of 10 PIECES of a penicillinic disk <24 mm should be tested for sensitivity to ertapeny by method of definition of MPK. Criteria of interpretation of a penicillinic diskodiffuzionny method are not applicable for viridans group streptococci which should not be tested concerning an ertapenem.

е These standards of interpretation are applicable to the procedure of a mikrodilyution of broth with use of the Haemophilus Test Medium (HTM) environment, inokulirovanny suspension of pure colony with an incubation on air at a temperature of 35 °C during 20-24 h.

f These diameters of zones are applicable to tests with use of a diskodiffuzionny method for NTM an agar, inokulirovanny suspension of pure colonies with an incubation in 5% of CO2 at 35 °C during 16-18 h.

g These standards of interpretation are applicable only to an agar dilyution with use of an agar of Brucella, with addition of hemin, K1 vitamin and 5% of the defibrinated or gemolizirovanny blood of a ram, inokulirovanny suspension of pure colony, or 6-24-hour fresh culture in the Wednesday enriched with thioglycollate at an incubation in an anaerobic container or the camera at 35-37 °C during 42-48 h.

Pharmacokinetics. Absorption. At administration of the solution in oil prepared from 1% or 2% by lidocaine solution ertapeny it is well absorbed from an injection site. Bioavailability makes about 92%. After introduction in oil in a dose of 1 g of Cmax it is reached approximately in 2 h.

Distribution. Ertapenem substantially contacts proteins of a blood plasma. Extent of binding decreases in process of increase in concentration of an ertapenem in plasma - approximately from 95% at concentration in plasma <100 mkg/ml to about 85% at concentration in plasma of 300 mkg/ml).

Average concentration (mkg/ml) in plasma of an ertapenem reached after single 30-minute in/in infusion of drug in a dose of 1 g or 2 g and after introduction in oil in a single dose of 1 g at healthy young adult volunteers are presented in table 2.

Table 2. Concentration of an ertapenem in plasma after introduction of a single dose.

* in/in infusion it was made at a constant speed within 30 min.

AUC of an ertapenem at adult patients increases almost in direct ratio to a dose (in the range of doses from 0.5 g to 2 g).

Cumulation of an ertapenem at adult patients after repeated in/in introductions (in the range of doses from 0.5 to 2 g/days) or introduction in oil on 1 g/days is not observed.

Vd of an ertapenem at adult patients - about 8 l (0.11 l/kg).

The concentration of an ertapenem in breast milk of the feeding women (5 people) defined daily in accidental temporary points within 5 days in a row after the last in/in administrations of drug in a dose of 1 g made: in the last day treatments (in 5-14 days after the delivery) <0.38 mkg/ml; by 5th day after the treatment termination 4 women had a concentration of an ertapenem a neopredelima, and at 1 woman - in trace quantities (<0.13 mkg/ml).

Ertapenem does not suppress the transport of digoxin and vinblastine mediated by the R-glycoprotein and itself is not its substrate.

Metabolism. Later in/in infusion of an ertapenem with an isotope tag in a dose of 1 g a radioactivity source in plasma is in the basic (94%) ertapeny. The main metabolite of an ertapenem represents derivative with not closed ring, formed at hydrolysis of a β-laktamny ring.

Removal. Ertapenem is brought mainly by kidneys. Average T1/2 at healthy adult young volunteers makes about 4 h of plasma. Later in/in introductions of an ertapenem with an isotope tag in a dose of 1 g to healthy young volunteers about 80% of drug are removed with urine, and 10% - with a stake. From 80% of the ertapenem defined in urine, about 38% are removed in not changed look, and about 37% - in the form of a metabolite with not closed β-laktamny ring.

At the healthy young volunteers who received ertapeny in/in in a dose of 1 g, average concentration of an ertapenem in urine during 0-2 h after introduction of this dose exceeds 984 mkg/ml, and during 12-24 h - exceeds 52 mkg/ml.

Pharmacokinetics in special clinical cases. Concentration of an ertapenem in plasma at men and women is comparable. In plasma later in/in introductions in a dose of 1 g and 2 g patients of advanced age have a concentration of an ertapenem (> 65 years) insignificantly above (approximately for 39% and 22% respectively), than at more young people (<65 years). Dose adjustment for patients of advanced age is not required.

Later in/in administrations of drug in a dose of 1 g/days concentration of an ertapenem in a blood plasma at children at the age of 13-17 years and adult patients is comparable. After purpose of drug in a dose of 20 mg/kg (to the maximum dose of 1 g) values of pharmacokinetic parameters at patients at the age of 13-17 years in general were comparable with those at healthy young volunteers. Three from six patients at the age of 13-17 years received a dose less than 1 g. For assessment of pharmacokinetic criteria at all patients of this group the received indicators were calculated taking into account that all patients received drug in a dose of 1 g, with an assumption of linear dependence. Results of comparison show that the pharmacokinetic profile at patients at the age of 13-17 years receiving ertapeny 1 g/days in a dose was comparable to that at adult patients. Ratios (patients at the age of 13-17 years/adults patients) for AUC values, made concentration at the end of introduction of infusion and concentration in the middle of an interval of dosing 0.99,1.2 and 0.84 respectively.

Concentration in a blood plasma in the middle of a dosing interval after single of introductions of an ertapenem in a dose of 15 mg/kg at children at the age of 3 months-12 of years are comparable with these concentration in the middle of a dosing interval later of administrations of drug in a dose of 1 g/days at adults. The clearance of an ertapenem from a blood plasma (ml/min.) at children at the age of 3 months-12 of years was approximately twice more in comparison with that at adult patients. At introduction in a dose of 15 mg/kg of AUC value at children at the age of 3 months-12 of years were comparable with these values at the young healthy volunteers receiving ertapeny in/in in a dose of 1 g. Average concentration (mkg/ml) in plasma of an ertapenem at children are presented to Tab. 3.

Table 3. Concentration of an ertapenem in plasma at children after introduction in a single dose *

* - in/in infusion it was made at a constant speed within 30 min.

** - to the maximum dose of 1 g/days

*** - to the maximum dose of 2 g/days

Vd at children aged from 3 months up to 12 years - 0.2 l/kg and about 0:16 l/kg at children at the age of 13-17 years.

Average T1/2 of an ertapenem at children and teenagers at the age of 13-17 years makes about 4 h of plasma, children aged from 3 months up to 12 years have about 2.5 h.

The pharmacokinetics of an ertapenem at patients with a liver failure was not studied. Due to the small intensity of his metabolism in a liver it is possible to expect that disturbance of its function should not influence pharmacokinetics of an ertapenem and correction of the mode of dosing with a liver failure it is not required from patients.

After single in/in introductions of an ertapenem in a dose of 1 g of AUC at patients with a renal failure of easy severity (KK from 60 to 90 ml/min. / 1.73 sq.m) does not differ from that at healthy volunteers (aged from 25 up to 82 years).

At patients with a renal failure of moderate severity (KK of 31-59 ml/min. / 1.73 sq.m) AUC is increased approximately by 1.5 times in comparison with healthy volunteers.

At patients with a renal failure of heavy degree (KK of 5-30 ml/min. / 1.73 sq.m) AUC is increased approximately by 2.6 times in comparison with healthy volunteers.

At patients with an end-stage of a renal failure (KK <10 ml/min. / 1.73 sq.m) AUC is increased approximately by 2.9 times in comparison with healthy volunteers. After single in/in introductions of an ertapenem in a dose of 1 g just before a hemodialysis session about 30% of the entered dose are defined in dialyzate. Data on use of drug for children with a renal failure are absent.

Patients with a renal failure of heavy degree or in an end-stage are recommended to carry out correction of the mode of dosing.

Indications to use:

Treatment heavy and moderate severity of the infectious and inflammatory diseases caused by sensitive strains of microorganisms (including for starting empirical antibacterial therapy before definition of activators):

— intraabdominal infections;

— infections of skin and hypodermic cellulose, including infections of the lower extremities at a diabetes mellitus (diabetic foot);

— community-acquired pneumonia;

— infections of an urinary system (including pyelonephritis);

— acute infections of bodies of a small pelvis (including puerperal endomyometritis, septic abortion and postoperative gynecologic infections);

— bacterial septicaemia.

Route of administration and doses:

The average daily dose of drug for adults and teenagers at the age of 13 years is also more senior makes 1 g, frequency rate of introduction - 1 times/days.

To children aged from 3 months up to 12 years Invanz® appoint in a dose 15 mg/kg 2 times in days (but no more than 1 g/days).

The drug is administered in the way to infusions or injections in oil. At in introduction duration of infusion has to make 30 min.

Introduction in oil can be an alternative in/in infusion.

The usual duration of therapy makes from 3 to 14 days depending on disease severity and a species of microorganisms. In the presence of clinical indications we will allow transition to the subsequent adequate peroral antibacterial therapy.

Drug can be used for treatment of infections at adult patients with a renal failure. With KK> 30 ml/min. / 1.73 the sq.m of correction of the mode of dosing is not required from patients. At patients with the expressed renal failures (KK30 ml/min. / 1.73 sq.m), including the patients who are on a hemodialysis, the recommended dose makes 500 mg/days. There are no data on use of drug for children with a renal failure.

The adult patients who are on a hemodialysis and received drug in a dose of 500 mg/days in the closest 6 h before a hemodialysis session should enter in addition 150 mg of drug after the session. If the drug is administered more than for 6 h to a hemodialysis, introduction of an additional dose is not required. There are no sufficient data according to the recommendation to the patients who are on peritoneal dialysis or haemo filtering now. There are no data on use of drug for the children who are on a hemodialysis.

If concentration of creatinine in serum is known, then it is possible to apply the following formulas to calculation of KK:

For men: KK = (body weight in kg) × (140 age advanced in years)/72×креатинин serums (mg/dl)

For women: KK = 0.85× (the size calculated for men)

With abnormal liver functions of dose adjustment it is not required from patients. The recommended dose can be entered without age (13 years and are more senior) and a floor.

Rules of preparation of solutions for parenteral administration. Adults and teenagers at the age of 13 years are also more senior. Preparation of solution for in/in infusion. Not to mix and not to enter together with other medicines. Not to use the thinners containing dextrose (glucose).

Before introduction lyophilisate needs to be dissolved, and then to part. Dissolve lyophilisate by addition to contents of 1 bottle of 10 ml of one of the following solvents: water for injections, 0.9% chloride sodium solution for injections or bacteriostatic water for injections. The bottle should be stirred up well and at once to add the recovered solution from a bottle to the prepared 50 ml of 0.9% of solution of sodium of chloride for infusions. Infusion has to be executed during 6 h after lyophilisate recovery.

Preparation of solution for an injection in oil. Before introduction lyophilisate needs to be dissolved. For preparation of solution for injections add 3.2 ml of 1% or 2% of solution of lidocaine of a hydrochloride for injections to bottle contents (1 g) (without Epinephrinum), then the bottle should be stirred up well for dissolution of contents. Bottle contents are gathered at once in the syringe and entered deeply into a large muscle (for example, into gluteuses or into lateral muscles of a hip). The prepared solution for introduction in oil has to be used during 1 h.

Children aged from 3 months up to 12 years. Preparation of solution for in/in infusion. Not to mix and not to enter together with other medicines. Not to use the thinners containing dextrose (glucose).

Before introduction lyophilisate needs to be dissolved, and then to part. Dissolve lyophilisate by addition to contents of 1 bottle of 10 ml of one of the following solvents: water for injections, 0.9% chloride sodium solution for injections or bacteriostatic water for injections. The bottle should be stirred up well and at once to gain the volume of solution, equivalent 15 mg/kg of body weight (but no more than 1 g/days) and to dilute in 0.9% chloride sodium solution for infusions to concentration 20 mg/ml or less. Infusion has to be executed during 6 h after lyophilisate recovery.

Preparation of solution for an injection in oil. Before introduction lyophilisate needs to be dissolved. For preparation of solution for injections add 3.2 ml of 1% or 2% of solution of lidocaine of a hydrochloride for injections to bottle contents (1 g) (without Epinephrinum), then the bottle should be stirred up well for dissolution of contents. At once it is necessary to select the volume equivalent to 15 mg/kg of body weight (but no more than 1 g/days) and to enter it deeply into a large muscle (for example, into gluteuses or into lateral muscles of a hip). The prepared solution for introduction in oil has to be used during 1 h.

The prepared solution for injections in oil cannot be used for in/in infusions. Medicines for parenteral administration before use need to be examined carefully for identification of suspended particles or changes of coloring. Color of solutions of the drug Invanz® varies from colourless to pale yellow (discoloration in these limits does not influence activity of drug).

Features of use:

Use at pregnancy and feeding by a breast. There is no sufficient clinical experience of use of the drug Invanz® at pregnancy. Drug should be used only when the estimated advantage of therapy for mother surpasses potential risk for a fruit.

With care it is necessary to use drug in the period of a lactation (breastfeeding) since ertapeny it is allocated with breast milk.

Use at abnormal liver functions. With abnormal liver functions of dose adjustment it is not required from patients.

Use at renal failures. Drug can be used for treatment of infections at patients with a renal failure. With KK> 30 ml/min. / 1.73 the sq.m of correction of the mode of dosing is not required from patients. At patients with the expressed renal failures (KK30 ml/min. / 1.73 sq.m), including the patients who are on a hemodialysis, the recommended dose makes 500 mg/days. There are no data on use of drug for children with a renal failure.

The adult patients who are on a hemodialysis and received drug in a dose of 500 mg/days in the closest 6 h before a hemodialysis session should enter in addition 150 mg of drug after the session. If the drug is administered more than for 6 h to a hemodialysis, introduction of an additional dose is not required. There are no sufficient data according to the recommendation the patient who is on peritoneal dialysis or haemo filtering now. There are no data on use of drug for the children who are on a hemodialysis.

Use for children. To children aged from 3 months up to 12 years Invanz® appoint in a dose 15 mg/kg 2 times in days (but no more than 1 g/days).

Purpose of drug aged up to 3 months is not recommended to children.

Use for elderly patients. In clinical trials efficiency and safety of the drug Invanz® at elderly people (≥65 years) were comparable to those at younger patients (≤65 years). Dose adjustment for patients of advanced age is not required.

Special instructions. Prolonged use of the drug Invanz®, as well as other antibiotics, can lead to the excess growth of insensitive microorganisms. At development of superinfection it is necessary to take the appropriate measures.

At use of almost all antibacterial drugs, including ertapeny, development of pseudomembranous colitis is possible (which main reason the toxin produced by Clostridium difficile is). Expressiveness of colitis can vary from a lung to life-threatening. It is necessary to consider a possibility of development of such complication when developing of the expressed diarrhea at the patients receiving antibacterial therapy.

At introduction in oil it is necessary to be careful to avoid accidental administration of drug in a blood vessel.

In clinical trials efficiency and safety of the drug Invanz® at patients of advanced age (≥65 years) were comparable to those at younger patients (≤65 years).

Use in pediatrics. Use of drug for children aged up to 3 months is not recommended.

Side effects:

The undesirable phenomena registered during treatment of patients by the drug Invanz® are classified by frequency as follows: frequent (≥1/100, <1/10), infrequent (≥1/1000, <1/100), rare (≥1/10 000, <1/1000), very rare (<1/10 000), frequency is unknown.

Adults. The undesirable phenomena (perhaps, possibly or definitely connected using drug), were noted approximately at 20% of the patients accepting ertapeny. Due to the undesirable phenomena ertapeny cancelled at 1.3% of patients.

The most frequent undesirable phenomena connected with parenteral administration of drug included diarrhea (4.8%), local complications later in introductions (4.5%) and nausea (2.8%).

From immune system: rare - allergic reactions; frequency is unknown - an anaphylaxis, including anaphylactoid reactions.

Infectious and parasitic diseases: infrequent - candidiasis of a mucous membrane of an oral cavity, candidiasis, a fungal infection, pseudomembranous colitis, a vaginitis; rare - pneumonia, a dermatomycosis, a postoperative wound fever, infections of an urinary system.

From system of a hemopoiesis: rare - a neutropenia, thrombocytopenia.

From a metabolism: rare - a hypoglycemia.

From TsNS: frequent - a headache; infrequent - sleeplessness, confusion of consciousness, dizziness, drowsiness, a food faddism, a convulsive attack; rare - agitation, uneasiness, a depression, a tremor, a syncope; frequency is unknown - the changed mental state (including aggression, a delirium, a disorientation, change of the mental status), hallucinations, dyskinesia, a myoclonia, gait disturbance.

From an organ of sight: rare - disturbances from scleras.

From cardiovascular system: frequent - a sinus bradycardia, post-infusional venous complications (phlebitis, thrombophlebitis); infrequent - decrease in the ABP; rare - arrhythmia, tachycardia, bleeding, increase in the ABP.

From respiratory system: infrequent - диспноэ, unpleasant feelings in a throat; rare - a nose congestion, nasal bleeding, rattles, the complicated breath.

From the alimentary system: frequent - diarrhea, nausea, vomiting; infrequent - a lock, an eructation acid contents, feeling of dryness in a mouth, dyspepsia, an abdominal pain; rare - a dysphagy, an incontience a calla, pelvic peritonitis, cholecystitis, jaundice, damage of a liver.

Dermatological reactions: rare - rash, an itch; infrequent - an erythema, a small tortoiseshell; rare - dermatitis, a skin peeling; frequency is unknown - medicinal rash with an eosinophilia and system symptoms (DRESS syndrome).

From a musculoskeletal system: rare - muscular spasms, shoulder pain; frequency is unknown - muscular weakness.

From an urinary system: rare - a renal failure, an acute renal failure.

From generative organs: genital bleeding.

From an organism in general and local reactions: infrequent - an ekstravazation, weakness, fatigue, fever, a stethalgia, anorexia; rare - consolidation in an injection site, an indisposition.

From laboratory indicators: frequent - increase in activity of ALT (4.6%), ACT (4.6%), ShchF (3.8%), increase in number of thrombocytes (3%); infrequent - increase in concentration of a direct and indirect bilirubin, creatinine, urea and glucose, reduction of quantity of leukocytes, thrombocytes, segmentoyaderny neutrophils, decrease in hemoglobin and a hematocrit, increase in quantity of eosinophils, AChTV and prothrombin time, increase in quantity of segmentoyaderny neutrophils and leukocytes, increase in quantity of bacteria, leukocytes, erythrocytes and epithelial cells in urine, a kandiduriya, positive reaction to Clostridium difficile toxin; rare - decrease in concentration of bicarbonates, creatinine, reduction of content of potassium, increase in activity of LDG, increase in content of phosphorus and potassium, reduction of quantity of lymphocytes, increase in quantity of band neutrophils, monocytes, myelocytes, atypical lymphocytes, increase in concentration of urobilinigen.

Children. The profile of efficiency and safety of the drug Invanz® at children was comparable to that at adult patients. The undesirable phenomena (perhaps, possibly or definitely connected using drug) were noted approximately at 20.8% of the patients accepting ertapeny. Due to the undesirable phenomena ertapeny cancelled at 0.5% of patients.

The most frequent undesirable phenomena connected using an ertapenem at its parenteral use included diarrhea (5.2%) and pain in an injection site (6.1%).

From TsNS: infrequent - a headache; frequency is unknown - hallucinations, the changed mental state (including aggression).

From cardiovascular system: infrequent - rush of blood, increase in the ABP.

From the alimentary system: frequent - diarrhea; infrequent - decolouration a calla, a melena.

Dermatological reactions: frequent - a diaper dermatitis; infrequent - an erythema, rash, petechias.

Local reactions: frequent - pain in an injection site; infrequent - burning, an itch, an erythema and a caumesthesia in an injection site.

From laboratory indicators: frequent - a neutropenia (3%), increase in activity of ALT (2.9%), ACT (2.8%); infrequent - increase in quantity of thrombocytes, AChTV and prothrombin time, decrease in hemoglobin.

Interaction with other medicines:

At use of an ertapenem with probenitsidy the last competes for active canalicular secretion and thus inhibits renal excretion of an ertapenem. It leads to small, but statistically significant increase in T1/2 (19%) and expressivenesses of systemic action (25%). Correction of the mode of dosing is not required. Simultaneous use with T1/2, probenitsidy for increase, is not recommended.

The researches in vitro show what ertapeny does not inhibit the transport of digoxin and vinblastine mediated by the R-glycoprotein and is not substrate for this transport. The researches in vitro of microsomes of a liver of the person show what ertapeny does not inhibit the metabolism mediated by six main isoenzymes of P450 (CYP) cytochrome - 1A2, 2S9, 2S19, 2D6, 2E1 and ZA4. The interaction with medicines caused by inhibition of the R-glikoprotein-oposredovannogo removal of drugs or the CYP mediated removal of drugs is improbable.

Special clinical trials on interaction with other medicines, except a probenetsid, it was not carried out.

The clinical cases described in literature show that simultaneous use of karbapenem, including ertapeny, with valproic acid or divalproatum of sodium lead to decrease in concentration of valproic acid. As a result of this interaction concentration of valproic acid can fall below therapeutic level that increases risk of development of a convulsive attack. Though the mechanism of interaction is unknown, yielded by in vitro and results of pilot studies on animals allow to assume that karbapenema can inhibit hydrolysis as a result of which the glyukuronidny metabolite of valproic acid (VPA-g) turns back into valproic acid that leads to decrease in concentration of valproic acid in a blood plasma.

Increase in a dose of valproic acid or divalproatum of sodium can be insufficient for overcoming effects of interaction. Simultaneous use of an ertapenem and valproyevy acid / Valproatum of sodium is not recommended. It is necessary to consider the possibility of treatment of infections antibiotics of other groups (not karbapenem) at patients who for control of convulsive attacks accept valproic acid or divalproatum of sodium. In need of use of the drug Invanz® performing additional anticonvulsant therapy can be required.

Contraindications:

— the established hypersensitivity to components of drug or to other antibiotics of the same group;

— hypersensitivity to others beta лактамным to antibiotics.

When using as solvent of lidocaine of a hydrochloride in oil administration of drug is contraindicated to patients with the established hypersensitivity to amide anesthetics of local action, patients with heavy arterial hypotension or with disturbance of endocardiac conductivity.

Overdose:

There is no special information on overdose of drug. In clinical trials accidental administration of drug by the adult in a dose to 3 g/days did not lead to clinically significant undesirable phenomena. In clinical trials single in/in administration of drug in a dose from 40 mg/kg to 2 g as much as possible did not cause toxic reactions in children.

Treatment: drug it is necessary to cancel and carry out the general maintenance therapy (to full removal of an ertapenem from an organism). Drug can be removed from an organism by a hemodialysis, but information on use of a hemodialysis for treatment of overdose is not available.

Storage conditions:

Unopened bottles should be stored in the place, unavailable to children, at a temperature not above 25 °C. A period of validity – 2 years. The recovered solution for infusions, immediately divorced in 0,9% chloride sodium solution, it is possible to store at the room temperature (not above 25 °C) and to use during 6 h or to store during 24 h in the refrigerator (5 °C) and to use during 4 h after extraction from the refrigerator. Solutions of drug cannot be frozen. The prepared solution for injections in oil it is possible to store no more than 1 p.

Issue conditions:

According to the recipe

Packaging:

Bottles of colourless glass with a capacity of 20 ml (1) - a pack cardboard.