Invanz: instructions for use. Invanz: instructions for use Ertapenem trade name analogues
Ertapenem sodium. Lyophilisate for the preparation of solution for injection (in 1 vial - 1.213 g, which corresponds to the content of ertapenem 1 g).
pharmachologic effect
Ertapenem, an antibiotic from the carbapenem group, is a 1-beta-methyl-carbapenem, a long-acting beta-lactam antibiotic for parenteral administration with a broad spectrum of activity. The bactericidal activity of ertapenem is due to inhibition of cell wall synthesis and is mediated by its binding to penicillin binding proteins (PBPs). In Escherichia coli it shows strong affinity for PBPs 1a, 1b, 2, 3, 4 and 5, with a preference for PBPs 2 and 3.
Ertapenem has significant resistance to most classes of β-lactamases (including penicillinases, cephalosporinases and extended-spectrum 3-lactamases, but not metallo-β-lactamases).
Invanz is active in vitro against aerobic and facultative anaerobic gram-positive microorganisms: Staph, aureus (including penicillinase-producing strains), Str. agalactiae, Str. pneumoniae, Str. pyogenes. Many strains of Enterococcus faecalis and most strains of Enterococcus faecium are resistant. Active against aerobic and facultative anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including strains producing P-lactamase), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis.
Active against anaerobic microorganisms: Bacteroides fragilis and other Bacteroides, microorganisms of the genus Clostridium (except CI. difficile), microorganisms of the genus Eubacterium, microorganisms of the genus Peptostreptococcus, Porphyromonas asaccharolytica, microorganisms of the genus Prevotella, microorganisms of the genus Fusobacterium. Methicillin-resistant staphylococci, as well as many strains of Enterococcus faecalis and most strains of Enterococcus faecium are resistant to the drug.
It is also active against aerobic and facultative anaerobic gram-negative microorganisms: Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli (producing extended-spectrum β-lactamases), Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae (producing extended-spectrum P-lactamases), Morganella morgani, Proteus vulgaris, Serratia marcescens. Many strains of the microorganisms listed above, which are multiresistant to other antibiotics, such as penicillins, cephalosporins (including generation I) and aminoglycosides, are sensitive to invasion.
Pharmacokinetics
With intramuscular administration of a solution prepared with 1% or 2% lidocaine solution, ertapenem is well absorbed from the injection site. Bioavailability - 92%. Ertapenem actively binds to human plasma proteins - 85% - 95% (the degree of binding depends on the concentration of ertapenem in plasma). Cumulation of ertapenem after repeated intravenous administration (in the dose range from 0.5 to 2 g/day) or intramuscular administration of 1 g/day is not observed.
Ertapinem undergoes metabolism. The main metabolite of ertapenem is a derivative formed during hydrolysis of the 3-lactam ring. T1/2 - 4 hours. Excreted: by the kidneys - 80% in the urine, about 38% is excreted unchanged, and about 37% is excreted as a metabolite; 10 % - with feces. Ertapenem is excreted from the breast. No dose adjustment is required for elderly patients.
The pharmacokinetics of ertapenem in patients with PN have not been studied. In patients with moderate PN (creatinine clearance 31-59 ml/min/1.73 m2), AUC is increased approximately 1.5 times compared to healthy volunteers. In patients with severe PN (creatinine clearance 5-30 ml/min/1.73 m2), AUC is increased approximately 2.6 times compared to healthy volunteers.
In patients with end-stage PN (creatinine clearance less than 10 ml/min/1.73 m2), AUC is increased approximately 2.9 times compared to healthy volunteers. After a single intravenous administration of ertapenem at a dose of 1 g immediately before a hemodialysis session, about 30% of the administered dose is determined in the dialysate.
Indications
Treatment of severe and moderate infectious and inflammatory diseases caused by sensitive strains of microorganisms (including for initial empirical antibacterial therapy until the pathogens are identified):
— infections of the abdominal organs, infections of the skin and subcutaneous tissue, including infections of the lower extremities with diabetes (diabetic foot), community-acquired;
— MS infections (including pyelonephritis);
- acute infections of the pelvic organs (including postpartum endomyometritis, septic abortion and postoperative gynecological infections);
- bacterial septicemia.
Application
The average daily dose of the drug for adults is 1 g, the frequency of administration is 1 r/day. The drug is administered by intravenous infusion or intramuscular injection. When administered intravenously, the infusion duration should be 30 minutes. IM administration may be an alternative to IV infusion.
The usual duration of therapy is from 3 to 14 days, depending on the severity of the disease and the type of microorganisms. If there are clinical indications, a transition to subsequent adequate oral antimicrobial therapy is acceptable.
The drug can be used to treat infections in patients with PN. In patients with CC more than 30 ml/min/1.73 m2, no dosage regimen adjustment is required. In patients with severe renal failure or in the terminal stage, it is recommended to adjust the dosage regimen: with severe renal impairment (CC Side effect
From the side of the central nervous system: often - headache; rarely - dizziness, drowsiness, insomnia, convulsions, confusion.
On PS: often - diarrhea, nausea, vomiting; rarely - candidiasis of the oral mucosa, constipation, belching with sour contents, pseudomembranous colitis (often manifested by diarrhea) caused by uncontrolled proliferation of Clostridium difficile, dry mouth, dyspepsia, anorexia.
On the cardiovascular system: rarely - decreased blood pressure.
From the side of the DS: rarely - dyspnea. Dermatological reactions: rarely - erythema, itching.
From the body as a whole: rarely - abdominal pain, taste perversion, weakness, fatigue, candidiasis, swelling, fever, chest pain.
Local reactions: often - post-infusion phlebitis (rhombophlebitis). From the genital organs: vaginal itching.
From laboratory parameters: often - increased ALT, AST, alkaline phosphatase, increased platelet count; rarely - increased direct, indirect and total bilirubin, increased number of eosinophils and monocytes, increased partial thromboplastin time, creatinine and blood glucose levels, decreased number of segmented neutrophils and leukocytes, decreased hematocrit, hemoglobin and platelet count, bacteriuria, increased serum urea nitrogen levels , number of epithelial cells in urine, number of erythrocytes in urine.
Contraindications
Hypersensitivity to the components of the drug or to other antibiotics of the same group, hypersensitivity to other beta-lactam antibiotics.
When lidocaine hydrochloride is used as a solvent, intramuscular administration of the drug is contraindicated in patients with established hypersensitivity to local amide anesthetics, patients with severe arterial hypotension or impaired intracardiac conduction.
Interaction with other drugs
Ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin and vinblastine and is not itself a substrate of P-glycoprotein. Ertapenem does not affect drug metabolism mediated by the main isoenzymes of cytochrome P450 - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4.
Interaction with drugs due to inhibition of tubular secretion, impaired binding to P-glycoprotein, or changes in the intensity of microsomal oxidation is unlikely. When ertapenem is prescribed together with drugs that block tubular secretion, no dosage adjustment is required.
Ertapenem sodium , sodium bicarbonate, sodium hydroxide.
Release form
Lyophilisate in the form of a powder of 1 g for the preparation of a white injection solution in transparent glass bottles of 20 ml in a cardboard box No. 1.
pharmachologic effect
Antibacterial.
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
The bactericidal activity of the drug is based on inhibition of the process of cell wall synthesis and is mediated by its ability to bind to PSB (penicillin-binding proteins ). Ertapenem resistant to hydrolysis beta-lactamases main classes, including cephalosporinases , penicillinase And beta-lactamases . Highly active against strains of facultative anaerobic and aerobic gram-positive and gram-negative microorganisms: Streptococcus pyogenes , Staphylococcus aureus , Streptococcus pneumoniae , Streptococcus agalactiae , Haemophilus influenzae , Escherichia coli , Bacteroides fragilis , Clostridium spp. , Eubacter spp. , Peptostreptococcus spp. , Аsaccharolytica Porphyromonas , Prevotella spp.
Many microorganisms with broad multidrug resistance to various antibiotics ( cephalosporins , penicillins , aminoglycosides , are highly sensitive to the drug.
Pharmacokinetics
The drug is quickly absorbed from the site of intramuscular injection. After administration at a dosage of 1 g Cmax achieved on average after 2.5 hours. Bioavailability of Invanz is about 92%, actively binds to blood proteins. Cumulation ertapenem when the drug is administered in therapeutic doses, it is absent in the body. Metabolized in the liver. It is excreted through the kidneys and in small amounts with feces. The average T1/2 from the blood is about 4 hours.
Indications for use
In the complex therapy of infectious and inflammatory diseases caused by strains of microorganisms sensitive to the drug: infections of the abdominal cavity and pelvic organs, skin and subcutaneous tissue, urinary system, community-acquired pneumonia , bacterial septicemia .
To prevent the development of surgical infections during colorectal surgery.
Contraindications
High sensitivity to the drug or to other beta-lactam antibiotics , age up to 3 months. When used for diluting lyophilisate, the drug is contraindicated in patients with severe arterial hypotension and with heart disease, accompanied by impaired intracardiac conduction. Use with caution during lactation.
Side effects
Nausea, vomiting, post-infusion , / , weakness/fatigue, decrease HELL , cramps, dry mouth, candidiasis oral mucosa, belching, abdominal pain, taste disturbance, itchy skin and rashes, vaginal candidiasis , swelling, increase, leukopenia , thrombocytopenia , erythrocyturia .
Invanz, instructions for use (Method and dosage)
The drug Invanz is administered as an intramuscular injection or intravenous infusion. The daily dose for adults and children over 12 years of age is on average 1 g, administered once a day. Children from 3 months to 12 years at a dosage of 15 mg/kg 2 times a day. The duration of the IV infusion is at least 30 minutes. The average duration of treatment is 3-14 days, depending on the type of disease, severity and type of pathogen.
Before administration, the drug powder must be dissolved and diluted. To prepare a solution for intravenous infusion, it is recommended to use sterile water or a 0.9% solution. When preparing Invanz solution for intravenous infusion, it is prohibited to mix the drug with other drugs, as well as use solvents that contain glucose .
To prepare a solution for intramuscular injection, a solution is used lidocaine hydrochloride . Inject deep into the lateral thigh muscles or gluteal muscles. You cannot use a ready-made solution for intramuscular injection to administer the drug intravenously.
Long-term treatment with Invanz may lead to the growth of microorganisms that are insensitive to the drug.
Overdose
There is no data on drug overdose.
Interaction
When used together ertapenem and drugs blocking tubular secretion , there is no need to change the dosage. Concomitant use ertapenem With sodium divalproate or valproic acid reduces concentration valproic acid , which increases the risk of a seizure. Reliable interaction data ertapenem with any medications, with the exception of
Terms of sale
On prescription.
Storage conditions
Store unopened vials at temperatures up to 25°C. Solutions of the drug cannot be frozen. Store the prepared solution for intramuscular injection for no more than 1 hour.
Best before date
24 months.
Invanza's analogs
Level 4 ATX code matches:Drugs with similar pharmacological effects include: Europenem , Lastinem , Mepenam , Inemplus , Merobicide , Meromec , Merospen , Let's prepenem , Ronham , Sinerpen and others.
Clinical and pharmacological group
06.014 (Antibiotic of the carbapenem group)Release form, composition and packaging
Lyophilisate for the preparation of solution for injection in the form of a powder or porous mass of white or almost white color.
Excipients: sodium bicarbonate, sodium hydroxide (up to pH 7.5); sodium content is approximately 137 mg (6 mEq).
Flat glass bottles with a capacity of 20 ml (1) - cardboard boxes.
pharmachologic effect
A carbapenem antibiotic, 1-β methyl-carbapenem is a long-acting beta-lactam antibiotic for parenteral administration with activity against a wide range of gram-positive and gram-negative aerobic and anaerobic bacteria.
The bactericidal activity of ertapenem is due to inhibition of cell wall synthesis and is mediated by its binding to penicillin binding proteins (PBPs). In Escherichia coli, it exhibits strong affinity for PBPs 1a, 1b, 2, 3, 4 and 5, with a preference for PBPs 2 and 3. Ertapenem has significant resistance to the action of most classes of β-lactamases (including penicillinases, cephalosporinases and β-lactamases extended spectrum, but not metallo-β-lactamase).
Invanz® is effective against most strains of the following microorganisms in vitro and in infections caused by them.
Active against aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus aureus (including strains that produce penicillinase /methicillin-resistant staphylococci are resistant/), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.
Many strains of Enterococcus faecalis and most strains of Enterococcus faecium are resistant.
Active against aerobic and facultative anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including strains producing β-lactamase), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis.
Active against anaerobic microorganisms: Bacteroides fragilis and other Bacteroides spp., microorganisms of the genus Clostridium (except Clostridium difficile), microorganisms of the genus Eubacterium, microorganisms of the genus Peptostreptococcus, Porphyromonas asaccharolytica, microorganisms of the genus Prevotella.
Invanz® with an MIC ≤ 2 μg/ml is active against the majority (≥ 90%) strains of microorganisms of the genus Streptococcus, including Streptococcus pneumoniae; with an MIC ≤ 4 μg/ml - against the majority (≥ 90%) strains of microorganisms of the genus Haemophilus, against the majority (> 90%) strains of aerobic and facultative anaerobic gram-positive microorganisms (Staphylococcus spp., coagulase-negative methicillin-sensitive /methicillin-resistant staphylococci resistant/, Streptococcus pneumoniae, penicillin-resistant Streptococcus viridans). The clinical significance of these in vitro MIC data is unknown.
Methicillin-resistant staphylococci, as well as many strains of Enterococcus faecalis and most strains of Enterococcus faecium are resistant to Invanz.
Also active against aerobic and facultative anaerobic gram-negative microorganisms: Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli (producing extended-spectrum β-lactamases), Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae (producing extended-spectrum β-lactamases), Morganella morgani, Proteus vulgaris, Serratia marcescens.
Many strains of the microorganisms listed above that are multiresistant to other antibiotics, for example, penicillins, cephalosporins (including third generation) and aminoglycosides, are sensitive to Invaz.
Active against anaerobic microorganisms of the genus Fusobacterium.
The determined MIC values must be interpreted in accordance with the criteria specified in the tables.
Table 1.
| Microorganisms | Dilution test (MIC in µg/ml) | ||
| Feels. | Died. | Resist. | |
| <4 | 8 | >16 | |
| Streptococcus pneumoniae | <2b | — | — |
| <2е | — | — | |
| Haemophilus spp.a | <4g | — | — |
| Anaerobes | <4i | 8 | >16 |
Table 2.
| Microorganisms | Disc diffusion test (zone diameter in mm) | ||
| Feels. | Died. | Resist. | |
| Aerobes and facultative anaerobes, except Streptococcus spp. and Haemophilus spp. | >16 | 13-15 | <12 |
| Streptococcus pneumoniae | >19c,d | — | — |
| Streptococcus spp., except S. pneumoniaea | >19c,f | — | — |
| Haemophilus spp.a | >18h | — | — |
| Anaerobes | - | — | — |
a The current lack of data on resistant strains makes it impossible to define any category as anything other than “susceptible”. If the MIC results of a strain can be interpreted as "non-susceptible", these strains require further investigation.
b Streptococcus pneumoniae, sensitive to penicillin (MIC<0.06 мкг/мл), могут считаться чувствительными к эртапенему. Тестирование изолятов с промежуточной чувствительностью к пенициллину или пенициллин-резистентных изолятов на чувствительность к эртапенему не рекомендуется, поскольку надежные критерии интерпретации для эртапенема отсутствуют.
c These zone diameter interpretation standards apply only to tests using Mueller-Hinton agar supplemented with 5% sheep blood inoculated with a suspension of pure colonies incubated in 5% CO2 at 35°C for 20-24 hours.
d Streptococcus pneumoniae isolates should be tested using a 1 μg oxacillin disk. Isolates with zone sizes ≥20 mm are susceptible to penicillin and may be considered susceptible to ertapenem.
e Streptococcus spp., which are sensitive to penicillin (MIC≤0.12 µg/ml) can be considered sensitive to ertapenem. Testing of isolates with intermediate susceptibility to penicillin or penicillin-resistant isolates for susceptibility to ertapenem is not recommended because reliable interpretative criteria for ertapenem are not available.
fStreptococcus spp. should be tested using a 10 unit penicillin disk. Isolates with zone sizes ≤28 mm are susceptible to penicillin and may be considered susceptible to ertapenem.
g These standards of interpretation apply to the broth microdilution procedure using Haemophilus Test Medium (HTM) inoculated with a pure colony suspension and incubated in air at temperature for 20-24 hours.
h These zone diameters apply to disc diffusion tests on HTM agar inoculated with a suspension of pure colonies and incubated in 5% CO2 at 35°C for 16-18 hours.
i These standards of interpretation apply only to agar dilution using Brucella agar, supplemented with hemin, vitamin K1 and 5% defibrinated or hemolyzed sheep blood inoculated with a pure colony suspension, or a 6-24 hour fresh culture in thioglycolate-enriched medium when incubated in an anaerobic environment. container or chamber at 35-37°C for 42-48 hours.
Pharmacokinetics
Suction
With intramuscular administration of a solution prepared with 1% or 2% lidocaine solution, ertapenem is well absorbed from the injection site. Bioavailability is approximately 92%. After intramuscular administration at a dose of 1 g, Cmax is achieved in approximately 2 hours.
Distribution
Ertapenem actively binds to human plasma proteins. The extent of binding decreases as plasma concentrations of ertapenem increase, from approximately 95% at plasma concentrations<100 мкг/мл до примерно 85% при концентрации в плазме 300 мкг/мл).
The mean plasma concentrations (μg/ml) of ertapenem achieved after a single 30-minute intravenous infusion of the drug at a dose of 1 g or 2 g and after intramuscular administration at a single dose of 1 g in healthy young adult volunteers are presented in the table.
| Dose | |||||
| 0.5 h | 1 hour | 2 hours | 4 hours | 6 hours | |
| IV administration* | |||||
| 1 g | 155 | 115 | 83 | 48 | 31 |
| 2 g | 283 | 202 | 145 | 86 | 58 |
| IM administration | |||||
| 1 g | 33 | 53 | 67 | 57 | 40 |
| Dose | Average plasma concentrations (µg/ml) | |||
| 8 hours | 12 h | 18 h | 24 hours | |
| IV administration* | ||||
| 1 g | 20 | 9 | 3 | 1 |
| 2 g | 36 | 16 | 5 | 2 |
| IM administration | ||||
| 1 g | 27 | 13 | 4 | 2 |
* IV infusion was performed at a constant speed for 30 minutes.
AUC increases almost directly proportional to the dose (in the dose range from 0.5 g to 2 g).
Cumulation of ertapenem after repeated intravenous administration (in the dose range from 0.5 to 2 g/day) or intramuscular administration of 1 g/day is not observed.
Vd of ertapenem is about 8 liters (0.11 l/kg).
The concentration of ertapenem in breast milk of lactating women (5 people), determined daily at random time points for 5 consecutive days after the last intravenous administration of the drug at a dose of 1 g, was: on the last day of treatment (5-14 days after birth)<0.38 мкг/мл; к 5 дню после прекращения лечения концентрация эртапенема у 4 женщин была неопределима, а у 1 женщины - в следовых количествах (<0.13 мкг/мл).
Ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin and vinblastine and is not itself a substrate of P-glycoprotein.
Metabolism
After an intravenous infusion of isotope-labeled ertapenem at a dose of 1 g, the source of radioactivity in the plasma is mainly (94%) ertapenem. The main metabolite of ertapenem is an open-ring derivative formed by hydrolysis of the β-lactam ring.
Removal
Ertapenem is excreted primarily by the kidneys. The average T1/2 from plasma in healthy young adult volunteers is approximately 4 hours. After intravenous administration of isotope-tagged ertapenem at a dose of 1 g to healthy young volunteers, about 80% of the tracer is excreted in the urine, and 10% in the feces. Of the 80% of ertapenem determined in urine, about 38% is excreted unchanged, and about 37% is excreted as a metabolite with an open β-lactam ring.
In healthy young adult volunteers who received ertapenem IV at a dose of 1 g, the average concentration of ertapenem in urine within 0-2 hours after administration of this dose exceeds 984 mcg/ml, and within 12-24 hours it exceeds 52 mcg/ml .
Pharmacokinetics in special clinical situations
Plasma concentrations of ertapenem are comparable in men and women.
Plasma concentrations of ertapenem following IV doses of 1 g and 2 g in older adult patients (over 65 years of age) are slightly higher (approximately 39% and 22%, respectively) than in younger adults. No dose adjustment is required for elderly patients.
Average plasma concentrations of ertapenem in children after a single dose* are presented in the table.
| Dose | Average plasma concentrations (µg/ml) | |||
| 0.5 h | 1 hour | 2 hours | 4 hours | |
| Children aged 3-23 months | ||||
| 15 mg/kg** | 103.8 | 57.3 | 43.6 | 23.7 |
| 20 mg/kg** | 126.8 | 87.6 | 58.7 | 28.4 |
| 40 mg/kg*** | 199.1 | 144.1 | 95.7 | 58.0 |
| Children aged 2-12 years | ||||
| 15 mg/kg** | 113.2 | 63.9 | 42.1 | 21.9 |
| 20 mg/kg** | 147.6 | 97.6 | 63.2 | 34.5 |
| 40 mg/kg*** | 241.7 | 152.7 | 96.3 | 55.6 |
| Children aged 13-17 years | ||||
| 15 mg/kg** | 170.4 | 98.3 | 67.8 | 40.4 |
| 1 g | 155.9 | 110.9 | 74.8 | - |
| 40 mg/kg*** | 255.0 | 188.7 | 127.9 | 76.2 |
| Dose | Average plasma concentrations (µg/ml) | |||
| 6 hours | 8 hours | 12 h | 24 hours | |
| Children aged 3-23 months | ||||
| 15 mg/kg** | 13.5 | 8.2 | 2.5 | - |
| 20 mg/kg** | - | 12.0 | 3.4 | 0.4 |
| 40 mg/kg*** | - | 20.2 | 7.7 | 0.6 |
| Children aged 2-12 years | ||||
| 15 mg/kg** | 12.8 | 7.6 | 3.0 | - |
| 20 mg/kg** | - | 12.3 | 4.9 | 0.5 |
| 40 mg/kg*** | - | 18.8 | 7.2 | 0.6 |
| Children aged 13-17 years | ||||
| 15 mg/kg** | - | 16.0 | 7.0 | 1.1 |
| 1 g | 24.0 | - | 6.2 | - |
| 40 mg/kg*** | - | 31.0 | 15.3 | 2.1 |
* - IV infusion was performed at a constant speed for 30 minutes.
** - up to a maximum dose of 1 g/day.
*** - up to a maximum dose of 2 g/day.
Vd of ertapenem in children aged 3 months to 12 years is 0.2 l/kg and about 0.16 l/kg in children aged 13-17 years.
The pharmacokinetics of ertapenem in patients with hepatic impairment have not been studied. Due to the low intensity of its metabolism in the liver, it can be expected that impaired liver function should not affect the pharmacokinetics of ertapenem and no dosage adjustment is required in patients with liver failure.
After a single intravenous administration of ertapenem at a dose of 1 g, AUC in patients with mild renal failure (creatinine clearance from 60 to 90 ml/min/1.73 m2) does not differ from that in healthy volunteers (aged 25 to 82 years).
In patients with moderate renal failure (creatinine clearance 31-59 ml/min/1.73 m2), AUC is increased approximately 1.5 times compared to healthy volunteers.
In patients with severe renal failure (creatinine clearance 5-30 ml/min/1.73 m2), AUC is increased approximately 2.6 times compared to healthy volunteers.
In patients with end-stage renal failure (CK<10 мл/мин/1.73 м2) AUC увеличена приблизительно в 2.9 раза по сравнению со здоровыми добровольцами. После однократного в/в введения эртапенема в дозе 1 г непосредственно перед сеансом гемодиализа около 30% введенной дозы определяется в диализате.
In patients with severe or end-stage renal failure, it is recommended that the dosage regimen be adjusted.
Dosage
The average daily dose of the drug for adults and adolescents aged 13 years and older is 1 g, the frequency of administration is 1 time/day.
For children aged 3 months to 12 years, Invanz® is prescribed at a dose of 15 mg/kg 2 times a day (but not more than 1 g/day).
The drug is administered by intravenous infusion or intramuscular injection. When administered intravenously, the infusion duration should be 30 minutes.
IM administration may be an alternative to IV infusion.
The usual duration of therapy is from 3 to 14 days, depending on the severity of the disease and the type of microorganisms. If there are clinical indications, it is permissible to switch to subsequent adequate oral antibacterial therapy.
The drug can be used to treat infections in patients with kidney failure. In patients with CC>
If the serum creatinine concentration is known, the following formulas can be used to calculate creatinine clearance:
For men:
CC = (body weight in kg) x (140-age in years)/72 x serum creatinine (mg/dl)
For women:
CC = 0.85 x (value calculated for men)
Rules for the preparation of solutions for parenteral administration
Adults and teenagers aged 13 years and older
The lyophilisate is reconstituted by adding 10 ml of one of the following solvents to the contents of 1 bottle: water for injection, 0.9% sodium chloride solution for injection or bacteriostatic water for injection. The bottle should be shaken well and immediately add the reconstituted solution from the bottle to the prepared 50 ml of 0.9% sodium chloride solution for infusion. The infusion should be performed within 6 hours after reconstitution of the lyophilisate.
To prepare the solution for injection, add 3.2 ml of 1% or 2% solution of lidocaine hydrochloride for injection (without epinephrine) to the contents of the bottle (1 g), then shake the bottle well to dissolve the contents. The contents of the vial are immediately drawn into a syringe and injected deep into a large muscle (for example, the gluteal muscles or the lateral thigh muscles). The prepared solution for intramuscular administration should be used within 1 hour.
Children aged 3 months to 12 years
Preparation of solution for intravenous infusion
Do not mix or administer with other medications. Do not use diluents containing dextrose (glucose).
Before administration, the lyophilisate must be reconstituted and then diluted.
The lyophilisate is reconstituted by adding 10 ml of one of the following solvents to the contents of 1 bottle: water for injection, 0.9% sodium chloride solution for injection or bacteriostatic water for injection. The bottle should be shaken well and immediately draw up a volume of solution equivalent to 15 mg/kg body weight (but not more than 1 g/day) and dilute in 0.9% sodium chloride solution for infusion to a concentration of 20 mg/ml or less. The infusion should be performed within 6 hours after reconstitution of the lyophilisate.
Preparation of solution for intramuscular injection
Before administration, the lyophilisate must be dissolved.
To prepare the solution for injection, add 3.2 ml of 1% or 2% solution of lidocaine hydrochloride for injection (without epinephrine) to the contents of the bottle (1 g), then shake the bottle well to dissolve the contents. A volume equivalent to 15 mg/kg body weight (but not more than 1 g/day) should be withdrawn immediately and injected deep into a large muscle (for example, the gluteal muscles or the lateral thigh muscles). The prepared solution for intramuscular administration should be used within 1 hour.
The reconstituted solution for intramuscular injection cannot be used for intravenous infusion.
Parenteral drug products should be carefully inspected for suspended particles or discoloration before use. The color of the solutions varies from colorless to pale yellow (color changes within these limits do not affect the activity of the drug).
Overdose
There is no specific information on drug overdose. In clinical studies, random administration of the drug at a dose of up to 3 g/day did not lead to clinically significant adverse events. In clinical studies in children, a single intravenous administration of the drug at a dose of 40 mg/kg to 2 g did not cause toxic reactions.
Treatment: the drug should be discontinued and general supportive therapy should be carried out (until ertapenem is completely eliminated from the body). The drug can be removed from the body by hemodialysis, but there is no information available on the use of hemodialysis to treat overdose.
Drug interactions
When ertapenem is prescribed together with drugs that block tubular secretion, no dosage adjustment is required.
Ertapenem does not affect drug metabolism mediated by the main isoenzymes of cytochrome P450 - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. Drug interactions due to inhibition of tubular secretion, impaired binding to P-glycoprotein, or changes in the intensity of microsomal oxidation are unlikely.
No specific clinical studies have been conducted on the interaction of ertapenem with specific drugs other than probenecid.
Use during pregnancy and lactation
There is no sufficient clinical experience with the use of Invanza during pregnancy. Prescribing the drug is possible only in cases where the expected benefit of therapy for the mother justifies the potential risk to the fetus.
The drug should be prescribed with caution during lactation (breastfeeding), because ertapenem is excreted in breast milk.
Side effects
Adults
Most adverse events reported during clinical trials were described as mild or moderate in severity. Due to adverse events that were suspected to be drug related, ertapenem was discontinued in 1.3% of patients.
The most common adverse events associated with parenteral administration of the drug included diarrhea (4.3%), local complications after IV administration (3.9%), nausea (2.9%) and headache (2.1%).
The following adverse events associated with the use of the drug have been reported with parenteral administration of ertapenem, and the following criteria for assessing the incidence of adverse events were used: often (<10%, но >1%); rarely (<1%, но >0.1%).
Local reactions: often - post-infusion phlebitis/thrombophlebitis.
From the side of the central nervous system: often - headache; rarely - dizziness, drowsiness, insomnia (0.2%), convulsions, confusion.
From the digestive system: often - diarrhea, nausea, vomiting; rarely - candidiasis of the oral mucosa, constipation, belching with sour contents, pseudomembranous colitis (often manifested by diarrhea) caused by uncontrolled proliferation of Clostridium difficile, dry mouth, dyspepsia, anorexia.
From the cardiovascular system: rarely - decreased blood pressure.
From the respiratory system: rarely - dyspnea.
Dermatological reactions: rarely - erythema, itching.
From the genital organs: vaginal itching.
From the body as a whole: rarely - abdominal pain, taste perversion, weakness/fatigue, candidiasis, swelling, fever, chest pain.
From laboratory parameters: often - increased ALT, AST, alkaline phosphatase, increased platelet count; rarely - an increase in direct, indirect and total bilirubin, an increase in the number of eosinophils and monocytes, an increase in partial thromboplastin time, creatinine and blood glucose levels, a decrease in the number of segmented neutrophils and leukocytes, a decrease in hematocrit, hemoglobin and platelet count; bacteriuria, increased serum urea nitrogen levels, the number of epithelial cells in the urine, and the number of red blood cells in the urine.
In most clinical studies, parenteral therapy preceded switching to a corresponding oral antibacterial drug. Over the entire treatment period and during 14 days of follow-up, adverse events associated with the use of Invanza included: often - rash, vaginitis (>1%); rarely - allergic reactions, general malaise, fungal infections (0.1% to 1.0%).
The most common adverse events associated with parenteral ertapenem included diarrhea (5.5%), injection site pain (5.5%), and injection site redness (2.6%).
The following drug-related adverse events have been reported during parenteral treatment of children with ertapenem:
From the digestive system: rarely - diarrhea, vomiting.
Dermatological reactions: rarely - rash.
Local reactions: rarely - erythema, pain at the injection site, phlebitis, local post-injection reaction.
From laboratory parameters: often - neutropenia; rarely - increased ALT, AST, leukopenia, eosinophilia.
Serious and fatal anaphylactic reactions have been rarely reported in patients treated with beta-lactam antibiotics. These reactions are more likely in individuals with a history of multivalent allergies (in particular, individuals with hypersensitivity to penicillin often develop severe hypersensitivity reactions when treated with other beta-lactams). Before starting treatment with Invanz®, the patient should be carefully asked about previous hypersensitivity reactions to other allergens, especially penicillins, cephalosporins and other beta-lactams.
If an allergic reaction occurs to the administration of Invanz®, it should be discontinued immediately. Serious anaphylactic reactions require emergency treatment.
Storage conditions and periods
Unopened bottles should be stored out of the reach of children at a temperature not exceeding 25°C. Shelf life – 2 years.
The reconstituted solution for infusion, immediately diluted in 0.9% sodium chloride solution, can be stored at room temperature (not above 25°C) and used within 6 hours or stored for 24 hours in the refrigerator (5°C) and used within 4 hours after removal from the refrigerator. Solutions of the drug should not be frozen.
The prepared solution for intramuscular injection can be stored for no more than 1 hour.
Indications
Treatment of severe and moderate infectious and inflammatory diseases caused by sensitive strains of microorganisms (including for initial empirical antibacterial therapy until the pathogens are identified):
- intra-abdominal infections;
- infections of the skin and subcutaneous tissue, including infections of the lower extremities in diabetes mellitus (diabetic foot);
— community-acquired pneumonia;
- infections of the urinary system (including pyelonephritis);
- acute infections of the pelvic organs (including postpartum endomyometritis, septic abortion and postoperative gynecological infections);
- bacterial septicemia.
Contraindications
- established hypersensitivity to the components of the drug or to other antibiotics of the same group;
- hypersensitivity to other beta-lactam antibiotics.
When lidocaine hydrochloride is used as a solvent, intramuscular administration of the drug is contraindicated in patients with established hypersensitivity to local amide anesthetics, patients with severe arterial hypotension or impaired intracardiac conduction.
special instructions
Long-term use of Invanza, like other antibiotics, can lead to excessive growth of insensitive microorganisms. If superinfection develops, appropriate measures should be taken.
When using almost all antibacterial drugs, including ertapenem, the development of pseudomembranous colitis (the main cause of which is a toxin produced by Clostridium difficile) is possible. The severity of colitis can range from mild to life-threatening. The possibility of developing such a complication should be taken into account when severe diarrhea occurs in patients receiving antibacterial therapy.
When administered intramuscularly, care should be taken to avoid accidental injection of the drug into a blood vessel.
In clinical studies, the effectiveness and safety of the drug in elderly people (over 65 years of age) were comparable to those in younger patients.
Use in pediatrics
Prescribing the drug to children under 3 months of age is not recommended.
Use for renal impairment
The drug can be used to treat infections in patients with kidney failure. In patients with CC>30 ml/min/1.73 m2, no dosage regimen adjustment is required. In patients with severe renal impairment (creatinine clearance≤30 ml/min/1.73 m2), including patients on hemodialysis, the recommended dose is 500 mg/day. There is no data on the use of the drug in children with renal failure.
Adult patients on hemodialysis who received the drug at a dose of 500 mg/day in the next 6 hours before the hemodialysis session should additionally administer 150 mg of the drug after the session. If the drug is administered more than 6 hours before hemodialysis, no additional dose is required. Currently, there is insufficient data on recommendations for patients undergoing peritoneal dialysis or hemofiltration. There is no data on the use of the drug in children undergoing hemodialysis.
Use for liver dysfunction
In patients with impaired liver function, no dose adjustment is required. The recommended dose can be administered without regard to age and gender.
Conditions for dispensing from pharmacies
The drug is available with a prescription.
Registration numbers
. lyophilisate for preparation. injection solution 1 g: fl. 1 PC. P No. 014496/01-2002 (2014-08-08 - 0000-00-00)Catad_pgroup Antibiotics carbapenems and monobactams
Invanz - instructions for use
Registration number P No. 014496/01-2002 dated October 30, 2002
Tradename: INVANZ® International nonproprietary name:
Ertapenem Dosage form:
lyophilisate for the preparation of solution for injection (for intravenous and intramuscular administration).
DESCRIPTION
Powder or porous mass of white or almost white color.
COMPOUND
Active substance: Each vial contains 1.213 grams of ertapenem sodium, which is equivalent to 1 gram of ertapenem free acid. Inactive substances: sodium bicarbonate - 203 mg, sodium hydroxide to pH 7.5. The sodium content is approximately 137 mg (approximately 6 mEq).
PHARMACODYNAMIC GROUP
Antibiotic, carbapenem. PBX code: J01DH.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamics/microbiology
Pharmacodynamics/Microbiology. Ertapenem - 1-? methyl carbapenem, a long-acting parenteral beta-lactam antibiotic with activity against a wide range of gram-positive and gram-negative aerobic and anaerobic bacteria.
The bactericidal activity of ertapenem is due to inhibition of cell wall synthesis and is mediated by its binding to penicillin binding proteins (PBPs). In Escherichia coli, it exhibits strong affinity for PBPs 1a, 1b, 2, 3, 4 and 5, with a preference for PBPs 2 and 3. Ertapenem has significant resistance to hydrolysis by most classes of beta-lactamases, including penicillinases, cephalosporinases and beta-lactamases extended spectrum, but not metallo-?-lactamase.
INVANZ is effective against most strains of the following microorganisms in vitro and against infections caused by them in clinical situations (see Indications for Use):
Aerobic and facultative anaerobic gram-positive microorganisms:
- Staphylococcus aureus (including penicillinase-producing strains, methicillin-resistant staphylococci are resistant)
- Streptococcus agalactiae
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Many strains of Enterococcus faecalis and most strains of Enterococcus faecium are resistant.
- Escherichia coli
- Haemophilus influenzae (including β-lactamase producing strains)
- Klebsiella pneumoniae
- Moraxella catarrhalis
- Proteus mirabilis
- Bacteroides fragilis and other species of the Bacteroides group
- Microorganisms of the genus Clostridium (except C. difficile)
- Microorganisms of the genus Eubacterium
- Microorganisms of the genus Peptostreptococcus
- Porphyromonas asaccharolytica
- Microorganisms of the genus Prevotella
INVANZ® at minimum inhibitory concentrations (MIC) =90%) of strains of microorganisms of the genus Streptococcus, including Streptococcus pneumoniae, at a concentration of =90%) of strains of microorganisms of the genus Haemophilus and at a concentration of =90%) of strains of other microorganisms from the list below.
Aerobic and facultative anaerobic gram-positive microorganisms:
- Microorganisms of the genus Staphylococcus, coagulase-negative, sensitive to methicillin (methicillin-resistant staphylococci are resistant)
- Streptococcus pneumoniae, penicillin-resistant
- Streptococci viridans
Aerobic and facultative anaerobic gram-negative microorganisms:
- Citrobacter freundii
- Enterobacter aerogenes
- Enterobacter cloacae
- Escherichia coli producing ESBLs (extended spectrum β-lactamases)
- Haemophilus parainfluenzae
- Klebsiella oxytoca
- Klebsiella pneumoniae producing ESBLs
- Morganella morganii
- Proteus vulgar is
- Serratia marcescens
Anaerobic microorganisms: Microorganisms of the genus Fusobacterium
Determined MIC values must be interpreted in accordance with the criteria specified in Table 1.
Table 1.
| Susceptibility criteria for Ertapenem | ||||||
| Dilution test(MIC in µg/ml) | Disc diffusion test (Zone diameter in mm) | |||||
| Microorganisms | Feels. | Moderate. | Resist. | Feels. | Moderate. | Resist. |
| Aerobes and facultative anaerobes, except Streptococcus spp. and Haemophuus spp. | <=4 | 8 | >=16 | >=16 | 13-15 | <=12 |
| Streptococcus pneumoniae | <=2 b | - | - | >=19 s,d | - | - |
| Streptococcus spp. except S. Pneumoniae a | <=2 e | - | - | >=19 s,f | - | - |
| Haemophilus spp.a | <=4 g | - | - | >=18 h | - | - |
| Anaerobes | <=4 i | 8 | >=16 | - | - | - |
a The current lack of data on resistant strains makes it impossible to define any category as anything other than “susceptible.” If the MIC results of a strain can be interpreted as "non-susceptible", these strains require further investigation.
b Streptococcus pneumoniae sensitive to penicillin (MIC? 0.06 μg/ml) may be considered sensitive to ertapenem. Testing of isolates with intermediate susceptibility to penicillin or penicillin-resistant isolates for susceptibility to ertapenem is not recommended because reliable interpretative criteria for ertapenem are not available.
With These zone diameter interpretation standards apply only to tests using Mueller-Hinton agar supplemented with 5% sheep blood inoculated with a suspension of pure colonies incubated in 5% CO2 at 35°C for 20-24 hours.
d Streptococcus pneumoniae isolates should be tested using a 1 μg oxacillin disk. Isolates with zone sizes? 20 mm is sensitive to penicillin and can be considered sensitive to ertapenem.
e Streptococcus spp., which are sensitive to penicillin (MIC? 0.12 μg/ml) can be considered sensitive to ertapenem. Testing of isolates with intermediate susceptibility to penicillin or penicillin-resistant isolates for susceptibility to ertapenem is not recommended because reliable interpretative criteria for ertapenem are not available.
f Streptococcus spp. should be tested using a 10 unit penicillin disk. Isolates with zone sizes? 28 mm is sensitive to penicillin and can be considered sensitive to ertapenem.
g These standards of interpretation apply to the broth microdilution procedure using Haemophilus Test Medium (HTM) inoculated with a pure colony suspension and incubated in air at temperature for 20 to 24 hours.
h These zone diameters apply to disc diffusion tests on HTM agar inoculated with a suspension of pure colonies and incubated in 5% CO2 at 35°C for 16-18 hours.
i These standards of interpretation apply only to agar dilution using Brucella agar, supplemented with hemin, vitamin K1, and 5% defibrinated or hemolyzed sheep blood inoculated with a pure colony suspension, or a 6-24 hour fresh culture in thioglycolate-enriched medium when incubated in an anaerobic container, or chamber at 35-37° C for 42-48 hours.
PHARMACOKINETICS
Suction
Ertapenem, dissolved in 1% or 2% lidocaine solution, is well absorbed after intramuscular administration at the recommended dose of 1 g. Bioavailability is approximately 92%. After intramuscular administration of 1 g per day, the maximum plasma concentration (Cmax) is reached after approximately 2 hours (Tmax).
Distribution
Ertapenem is actively bound to human plasma proteins (the protein binding of ertapenem decreases as its plasma concentration increases from approximately 95% at a plasma concentration of 00 mcg/ml to approximately 85% at a plasma concentration of 300 mcg/ml). The mean plasma concentrations (μg/mL) of ertapenem following a single 30-minute IV infusion of 1 g or 2 g and a single 1 g IM dose in healthy young adult subjects are presented in Table 2.
Plasma concentration of ertapenem after administration after single dose administration
| Dose - Route of administration | Average plasma concentrations (µg/ml) | ||||||||
| 0.5 h | 1 hour | 2 hours | 4 hours | 6 hours | 8 hours | 12 h | 18 h | 24 hours | |
| 1 g - i/v* | 155 | 115 | 83 | 48 | 31 | 20 | 9 | 3 | 1 |
| 1 g - i/m | 33 | 53 | 67 | 57 | 40 | 27 | 13 | 4 | 2 |
| 2 g - i/v* | 283 | 202 | 145 | 86 | 58 | 36 | 16 | 5 | 2 |
* IV infusion was carried out at a constant rate for 30 minutes. The area under the pharmacokinetic concentration-time curve of ertapenem in plasma (AUC) increases almost directly proportional to the dose in the dose range from 0.5 g to 2 g. Cumulation of ertapenem after repeated i.v. In administration of doses in the range from 0.5 to 2 g per day or intramuscular administration of 1 g per day is not observed.
The concentration of ertapenem in breast milk of lactating women (5 people), determined daily at random time points for 5 consecutive days after the last intravenous dose of 1 g, was: on the last day of treatment (5-14 days after birth)<0.38 мкг/мл. К 5-му дню после прекращения лечения концентрация эртапенема у 4 женщин была неопределима, а у 1 женщины - в следовых количествах (<0.13 мкг/мл).
Ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin and vinblastine and is not itself a substrate for this transport (see Interactions with Other Drugs).
Metabolism
After an intravenous infusion of 1 g of isotope-labeled ertapenem, the source of radioactivity in the plasma is mainly (94%) ertapenem. The main metabolite of ertapenem is an open-ring derivative formed by hydrolysis of the β-lactam ring.
Removal
Ertapenem is excreted primarily by the kidneys. The mean plasma half-life in healthy young adult subjects is approximately 4 hours.
After IV administration of 1 g of isotope-labeled ertapenem to healthy young adult subjects, approximately 80% of the drug is excreted in the urine and 10% in the feces. Of the 80% of ertapenem determined in urine, about 38% is excreted as unchanged drug, and about 37% is excreted as an open-ended metabolite. -lactam ring.
In healthy young adult subjects receiving a 1 g IV dose, the mean urinary concentration of ertapenem within 0-2 hours after administration of this dose exceeded 984 mcg/ml, and within 12-24 after administration of this dose exceeded 52 mcg/ml .
Features of pharmacokinetics in certain groups of patients:
Floor. Plasma concentrations of ertapenem are comparable in men and women.
Elderly patients. Plasma concentrations of ertapenem following IV doses of 1 g and 2 g in older adults (>= 65 years) are not significantly higher (approximately 39% and 22%, respectively) than in younger adults. No dose adjustment is required for elderly patients.
Children. The pharmacokinetics of ertapenem in children has not been studied.
Patients with liver failure. The pharmacokinetics of ertapenem in patients with hepatic impairment have not been studied. Due to its low intensity of metabolism in the liver, it can be expected that impaired liver function should not affect the pharmacokinetics of ertapenem and no dosage adjustment is required in patients with liver failure.
Patients with renal failure. After a single intravenous administration of 1 g of ertapenem, AUC in patients with mild renal failure (creatinine clearance Clcr 60-90 ml/min/1.73 m2) does not differ from that in healthy subjects (aged 25 to 82 years).
In patients with moderate renal failure (Clcr 31-59 ml/min/1.73 m2), AUC is increased approximately 1.5 times compared to healthy subjects.
In patients with severe renal failure (Clcr 5-30 ml/min/1.73 m2), AUC is increased approximately 2.6 times compared to healthy subjects.
In patients with end-stage renal failure (Clcr< 10 мл/мин/1.73 м2) AUC увеличена приблизительно в 2.9 раза по сравнению со здоровыми испытуемыми. После однократного в/в введения разовой дозы 1 г эртапенема непосредственно перед сеансом гемодиализа около 30% введенной дозы определяется в диализате.
In patients with severe and end-stage renal failure, it is recommended to adjust the dosage regimen (see Dosage and Administration).
INDICATIONS FOR USE
INVANZ is indicated for the treatment of adult patients with severe and moderate infections caused by sensitive strains of microorganisms (including for initial empirical antibiotic therapy until bacterial pathogens are identified for the following infections):
- Intra-abdominal infections;
- Infections of the skin and subcutaneous tissue, including infections of the lower extremities in diabetes mellitus (“diabetic” foot);
- Community-acquired pneumonia;
- Urinary system infections, including pyelonephritis;
- Acute infections of the pelvic organs, including postpartum endomyometritis, septic abortion and post-surgical gynecological infections;
- Bacterial septicemia.
CONTRAINDICATIONS
INVANZ is contraindicated in patients with known hypersensitivity to any of its components or to other drugs of the same class, as well as in patients who have had allergic reactions to other beta-lactam antibiotics.
When lidocaine hydrochloride is used as a diluent, intramuscular administration of INVANZ a is contraindicated in patients with known hypersensitivity to amide local anesthetics, patients with severe hypotension or intracardiac conduction disturbances (See information for physicians on the medical use of lidocaine hydrochloride).
Use during pregnancy
There is not sufficient clinical experience with the use of the drug in pregnant women. INVANZ should be used during pregnancy only if the potential benefit of treatment justifies the potential risk to the fetus.
Use during breastfeeding
Ertapenem is secreted into human milk (see Pharmacokinetics, Distribution). Caution should be exercised when prescribing INVANZ to breastfeeding women.
Use in children
Safety and effectiveness in children have not been studied (use in patients under 18 years of age is not recommended).
Use in elderly patients
In clinical studies, the efficacy and safety of INVANZ in older adults (>=65 years) were comparable to those in younger patients.
METHOD OF APPLICATION AND DOSES
The usual daily dose of INVANZ for adults is 1 g, the frequency of administration is 1 time per day.
INVANZ can be administered by intravenous (IV) infusion or intramuscular (IM) injection. For intravenous infusion of INVANZA, the infusion duration should be 30 minutes.
Intramuscular administration of INVANZ can be used as an alternative to intravenous infusion.
The usual duration of therapy with INVANZ ranges from 3 to 14 days, varying depending on the type of disease and the pathogenic microorganism(s) that caused it (See Indications for Use). If there are clinical indications (clinical improvement), a transition to subsequent adequate oral antimicrobial therapy is acceptable.
Patients with kidney failure: INVANZ may be used to treat infections in patients with kidney failure. In patients with creatinine clearance more than 30 ml/min/1.73 m2, no dosage adjustment is required. Patients with severe renal failure (creatinine clearance less than or equal to 30 ml/min/1.73 m2), including those on hemodialysis, should receive 500 mg per day.
Patients on hemodialysis: Patients on hemodialysis who received the recommended daily dose of INVANZ® 500 mg in the next 6 hours before the hemodialysis session, after which an additional 150 mg of the drug must be administered. If INVANZ is administered more than 6 hours before hemodialysis, no additional dose is required. Currently, there is insufficient data on recommendations for patients undergoing peritoneal dialysis or hemofiltration.
If the serum creatinine concentration is known, the following formulas can be used to calculate creatinine clearance:
Men:[(weight in kg) x (140-age in years)]/[(72) x serum creatinine (mg/100 ml)]
Women:(0.85) x (value calculated for men)
For patients with impaired liver function, no dose adjustment is required (see Pharmacological properties, Features of pharmacokinetics in certain groups of patients, Liver failure).
The recommended dose of INVANZ can be administered without regard to age or gender.
INSTRUCTIONS FOR PREPARATION OF SOLUTION
Preparation of solution for intravenous infusion
Do not mix or administer with other medications. Do not use diluents containing dextrose (a-d-glucose).
Before administration, INVANZ must be reconstituted and then diluted.
1. Reconstitute the contents of a 1 g vial of INVANZA by adding 10 ml of one of the following diluents: water for injection, 0.9% sodium chloride solution for injection, or bacteriostatic water for injection.
2. Shake the vial well to dissolve and immediately add the reconstituted solution from the vial to the prepared 50 ml of 0.9% sodium chloride solution for infusion.
3. The infusion should be completed within 6 hours after reconstitution of INVANZ.
Preparation of solution for intramuscular injection
Before administration, INVANZ must be dissolved
1. Dissolve the contents of the bottle containing
1 g INVANZA, in 3.2 ml of 1% or 2% lidocaine solution. Shake the bottle well to dissolve the contents.
2. Immediately draw the contents of the vial into the syringe and inject it deeply intramuscularly into a large muscle mass (for example, into the gluteal muscles or lateral thigh muscles).
3. The prepared solution for intramuscular administration should be used within 1 hour.
Parenteral medicinal products should be visually inspected before use to identify suspended particles or discoloration. The color of INVANZ solutions varies from colorless to pale yellow (color changes within these limits do not affect the activity of the drug).
SIDE EFFECT
Most adverse events reported during clinical trials were described as mild or moderate in severity. Due to adverse events that were suspected to be drug related, ertapenem was discontinued in 1.3% of patients.
The most common adverse events associated with parenteral ertapenem included diarrhea (4.3%), local post-infusion venous complications (3.9%), nausea (2.9%) and headache (2.1%).
During parenteral treatment of patients with ertapenem, the following adverse events associated with the use of the drug were reported: Frequent (>=1/100, Nervous system: Headache
Local reactions: Post-infusion phlebitis/thrombophlebitis
Gastrointestinal tract: Diarrhea, nausea, vomiting
Rare (>1/1000, Nervous system: Dizziness, drowsiness, insomnia, convulsions, confusion
The cardiovascular system: Reduced blood pressure.
Respiratory system: Dyspnea
Gastrointestinal tract: Candidiasis of the oral mucosa, constipation, belching of sour contents, pseudomembranous colitis (often accompanied by diarrhea) caused by uncontrolled proliferation of C. difficile, dry mouth, dyspepsia, anorexia.
Skin and subcutaneous tissue: Erythema, itching
General and local (at the injection site) reactions: Abdominal pain, taste disturbance, weakness/fatigue, candidiasis, swelling, fever, chest pain.
Reproductive system: Vaginal itching
Nervous system: Convulsions (0.2% of patients).
In most clinical studies, parenteral therapy preceded switching to a corresponding oral antimicrobial agent. During the entire treatment period and during the 14-day follow-up, adverse events associated with the use of INVANZ also included rash and vaginitis with an incidence of 1% (common) and allergic reactions, general malaise and fungal infections with an incidence of 0.1% to 1% (common). .0% (rare).
Serious, even fatal, anaphylactic reactions have been reported in patients treated with beta-lactam antibiotics. These reactions are more likely in individuals with a history of multivalent allergies (in particular, individuals with hypersensitivity to penicillin often develop severe hypersensitivity reactions when treated with other beta-lactams). Before starting treatment with INVANZ, the patient should be carefully questioned about previous hypersensitivity reactions to other allergens, especially penicillins, cephalosporins and other beta-lactams.
If an allergic reaction to INVANZ occurs, it should be discontinued immediately. Serious anaphylactic reactions require emergency treatment.
Changes in laboratory parameters. The most commonly observed laboratory test abnormalities associated with INVANZ were increases in ALT, AST, alkaline phosphatase, and platelet counts.
Other laboratory test abnormalities associated with the use of the drug included the following: increases in direct, indirect and total bilirubin, eosinophil and monocyte counts, partial thromboplastin time, creatinine and glucose; decrease in the number of segmented neutrophils and leukocytes, decrease in hematocrit, hemoglobin and platelet count; increase in the number of bacteria in the urine, serum urea nitrogen, epithelial cells in the urine, red blood cells in the urine.
OVERDOSE
No specific information is available for the treatment of INVANZ overdose. In clinical studies, random administration of up to 3 g per day did not lead to clinically significant adverse events.
In case of overdose of INVANZ, it should be discontinued and general supportive treatment should be carried out until the drug is excreted by the kidneys.
INVANZ can be removed from the body by hemodialysis. However, there is no information on the use of hemodialysis to treat overdose.
INTERACTION WITH OTHER MEDICINES
When prescribing ertapenem together with drugs that block tubular secretion, no adjustment of the dosage regimen is required.
Ertapenem does not affect the metabolism of xenobiotics mediated by the six main isoforms of cytochrome P450 (CYP) - 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (see Interactions with other drugs). Drug interactions due to inhibition of tubular secretion, impaired binding to P-glycoprotein, or changes in the intensity of microsomal oxidation are unlikely.
No specific clinical studies have been conducted on interactions with specific drugs other than probenecid.
SPECIAL INSTRUCTIONS
Long-term use of INVANZ, like other antibiotics, can lead to excessive growth of non-susceptible microorganisms. If a superinfection develops during treatment, appropriate measures must be taken.
When using almost all antibacterial drugs, including ertapenem, the development of pseudomembranous colitis is possible, the severity of which can vary from mild to life-threatening. It is important to consider the possibility of such a diagnosis in patients presenting with diarrhea after administration of antibacterial drugs. Research shows that the main cause of "antibiotic-associated colitis" is a toxin produced by Clostridium difficile.
When administering INVANZ intramuscularly, care should be taken to avoid accidental injection into a blood vessel (see Dosage and Administration).
The solvent for intramuscular administration of INVANZ is a solution of lidocaine hydrochloride. Refer to information for physicians on the medical uses of lidocaine hydrochloride.
PACKAGE
INVANZ® is available in glass bottles with a capacity of 20 ml, sealed with rubber stoppers and crimped aluminum caps.
Each bottle with instructions for use is placed in a cardboard box.
STORAGE CONDITIONS
Unopened vials (before reconstitution):
Store at a temperature not exceeding 25 C, out of the reach of children.
Reconstituted solutions:
The reconstituted solution for infusion, immediately diluted in 0.9% sodium chloride (see Dosage and Administration, Instructions for Use), can be stored at room temperature (25° C) and used within 6 hours or stored for 24 hours in refrigerator (5° C) and use within 4 hours after removal from the refrigerator. INVANZ solutions should not be frozen.
The solution for intramuscular injection can be stored for no more than 1 hour.
BEST BEFORE DATE
18 months.
Do not use the drug after the expiration date, which is indicated on the package after the words “BEST BEFORE”.
CONDITIONS OF VACATION FROM PHARMACIES
By doctor's prescription.
The antibiotic Invanz ® is a representative of the pharmacological class of carbapenems, part of the group of beta-lactam antibiotics.
Carbapenems are distinguished by an exceptionally wide spectrum of antibacterial effects, high efficiency, relatively low toxicity and high bioavailability.
A representative of the newest group of carbapenem antibiotics is ertapenem (trade name Invanz ®), synthesized in 2002. Invanz ® (ertapenem) differs from other carbapenems by improved pharmacokinetics, which allows the drug to be used once a day, and an even wider spectrum of antimicrobial activity, including bacterial strains that produce extended-spectrum beta-lactamases.
The manufacturer of Invanza ® is the American pharmaceutical company Merck Sharp and Dome. The cost of one bottle of product containing lyophilisate (1 gram of antibiotic) for the preparation of an injection solution is 2,700 rubles.
The main active ingredient of Invanz ®, ertapenem, has an ultra-wide spectrum of antibacterial activity. The drug can be used to treat infections caused by bacteria resistant to cephalosporins, penicillins and aminoglycosides.
Invanz ® is highly effective against staphylo- and streptococcal flora, Escherichia, Haemophilus influenzae, Proteus, Moraxella, Bacteroides, Clostridia, Peptostreptococcus, etc.
Methicillin-resistant staphylococci and enterococci are resistant to the antibiotic.
Pharmacokinetic properties of Invanza ®
Ertapenem has high bioavailability and a high ability to penetrate into inflamed organs and tissues. It should be noted that the antibiotic can penetrate into breast milk and be excreted in significant concentrations. In this regard, it is recommended to temporarily stop breastfeeding during antibacterial therapy.
The antibiotic is eliminated from the body by the kidneys, so if the glomerular filtration rate decreases, adjustment of the prescribed dose may be necessary. Less than ten percent of the antibiotic is utilized in feces.
Pharmacological group Invanz ®
Ertapenem is part of the carbapenem group of beta-lactam antibiotics. All antibacterial agents of the carbapenem class have an ultra-wide spectrum of antimicrobial effects and resistance to the overwhelming number of bacterial beta-lactamase enzymes.
Release form Invanz ®
The antibacterial drug is available only in the form of a lyophilisate for the production of infusion solutions (bottles of 1000 milligrams of antibiotic). The drug can be administered intravenously by infusion or intramuscularly.
Ertapenem does not have any other forms of release (including those suitable for oral administration).
Composition of Invanza ®
In addition to the main active ingredient – ertapenem, Invanz ® contains auxiliary components. The manufacturer indicates the content of bicarbonate and sodium hydroxide in the product.
Invanz ® recipe in Latin
The antibacterial drug belongs to the reserve group, therefore it is used strictly as prescribed by a doctor.
Rp: Ertapenemum 1.0.
In some cases, there may be complaints of distortions of taste, the development of arterial hypotension, changes in peripheral blood parameters (the appearance of monocytosis, eosinophilia, thrombocytosis in blood tests) and biochemical analysis (an increase in the activity of liver enzymes is noted). Rarely, erythrocyturia may develop.
Insomnia, dizziness, confusion, weakness, dry mucous membranes, diarrhea and pseudomembranous colitis (rare) are also possible.
Allergic reactions when using ertapenem develop extremely rarely, as a rule, in patients with polyvalent allergies to all beta-lactam antibacterial drugs.
Alcohol compatibility
The antibiotic is strictly incompatible with alcoholic beverages. In addition to the fact that drinking alcohol during treatment increases the likelihood of side effects, such a combination reduces the effectiveness of antibiotic therapy.
Invanz ® during pregnancy
Large-scale controlled studies of the safety of ertapenem in pregnant women have not been conducted. However, an antibacterial agent can be used to treat this category of patients, in the absence of a safer alternative, after carefully balancing the risk for the baby and the benefit for the mother.
Breastfeeding should be temporarily stopped during treatment with Invanz ®, since the antibiotic can penetrate into breast milk and be excreted with it.
Analogues of Invanz ®
At the moment, Invanz ® is the only drug based on ertapenem. The drug has no analogues. The advisability of replacing ertapenem with another antibiotic from the carbopenem group: doripenem ® or meropenem ® should be determined by the attending physician.
