What is the antibiotic invanz used for? Invanz - description of the drug, instructions for use, reviews. Special instructions for admission

pharmachologic effect

An antibiotic from the group of carbapenems, is 1-β methyl-carbapenem, a long-acting beta-lactam antibiotic for parenteral administration. Possesses a wide range antibacterial action.
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 exhibits significant resistance to most classes of β-lactamases (including penicillinases, cephalosporinases, and β-lactamases). extended spectrum, but not metallo-β-lactamase).
Active towards aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus aureus (including strains producing penicillinase), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.
Active against aerobic and facultative anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including β-lactamase producing strains), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis.
Active in anaerobic microorganisms: Bacteroides fragilis and other Bacteroides spp., Clostridium spp. (except Clostridium difficile), Eubacterium spp., Peptostreptococcus spp., Porphyromonas asaccharolytica, Prevotella spp.
Methicillin-resistant staphylococci, as well as many strains of Enterococcus faecalis and most strains of Enterococcus faecium, are resistant to ertapenem.
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 β-lactamases), Morganella morgani, Proteus vulgaris, Serratia marcescens.
Many strains of the microorganisms listed above, which have multi-resistance to other antibiotics, such as penicillins, cephalosporins (including III generation) and aminoglycosides, are sensitive to ertapenem.
Active against anaerobic microorganisms Fusobacterium spp.

Pharmacokinetics

With the / m administration of a solution prepared with a 1% or 2% solution of lidocaine, ertapenem is well absorbed from the injection site. Bioavailability is approximately 92%. After i / m administration at a dose of 1 g, Cmax is reached after approximately 2 hours.
Ertapenem actively binds to human plasma proteins. The degree of binding decreases with increasing plasma concentration of ertapenem - from about 95% at plasma concentration<100 мкг/мл до примерно 85% при концентрации в плазме 300 мкг/мл).
AUC increases almost in direct proportion to dose (in the dose range from 0.5 g to 2 g).
Ertapenem accumulation 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.
Ertapenem is excreted in human breast milk.
Ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin and vinblastine and is not itself a substrate.
Following intravenous infusion of isotopically labeled ertapenem at a dose of 1 g, the source of radioactivity in plasma is mainly (94%) ertapenem. The major metabolite of ertapenem is an open-ring derivative formed by hydrolysis of the β-lactam ring.
Ertapenem is excreted mainly by the kidneys. The mean T 1 / 2 from plasma in healthy adult young volunteers is approximately 4 hours. After intravenous administration of isotopically labeled ertapenem at a dose of 1 g to healthy young volunteers, about 80% of the label is excreted in the urine, and 10% in the feces. Of the 80% of ertapenem detected 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 1 g IV ertapenem, mean urinary ertapenem concentrations exceed 984 μg/mL within 0-2 hours after this dose and exceed 52 μg/mL within 12-24 hours .
In patients with kidney failure moderate severity (CC 31-59 ml / min / 1.73 m 2) AUC increased by approximately 1.5 times compared with healthy volunteers.
In patients with severe renal insufficiency (CC 5-30 ml / min / 1.73 m 2), AUC is increased by approximately 2.6 times compared with healthy volunteers.
In patients with end-stage renal disease (CK<10 мл/мин/1.73 м 2) 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.

Indications for use

Treatment of severe and moderate infectious and inflammatory diseases caused by susceptible strains of microorganisms (including for initial empirical antibiotic therapy before determining pathogens): infections of the abdominal cavity; skin infections and subcutaneous tissue including infections lower extremities at diabetes("diabetic" foot); community-acquired pneumonia; infections of the urinary system (including pyelonephritis); acute infections pelvic organs (including postpartum endomyometritis, septic abortion and postoperative gynecological infections); bacterial septicemia.

Dosing regimen

Administered by intravenous infusion or intramuscular injection. With intravenous administration, the duration of the infusion should be 30 minutes. IM administration may be an alternative to IV infusion.
Medium daily dose the drug for adults is 1 g, the frequency of administration is 1 time / day.
The usual duration of therapy is from 3 to 14 days, depending on the severity of the disease and the type of microorganisms. In the presence of clinical indications allow transition to subsequent adequate oral antimicrobial therapy.
In patients with CC>
Patients on hemodialysis who received ertapenem at a dose of 500 mg/day in the next 6 hours before a hemodialysis session should receive an additional 150 mg of ertapenem after the session. If ertapenem is administered more than 6 hours before hemodialysis, no additional dose is required. There are currently no recommendations for patients on peritoneal dialysis or hemofiltration.

Side effect

From the side of the central nervous system: often - headache; rarely - dizziness, drowsiness, insomnia, convulsions, confusion.
From the side digestive system: often - diarrhea, nausea, vomiting; rarely - candidiasis of the oral mucosa, constipation, belching of acidic contents, pseudomembranous colitis (often manifested by diarrhea) caused by uncontrolled reproduction of Clostridium difficile , dry mouth, dyspepsia, anorexia.
From the side of cardio-vascular system: rarely - a decrease in blood pressure.
From the side respiratory system: rarely - dyspnea.
Dermatological reactions: often - rash; 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 / thrombophlebitis.
From the genitals: vaginal itching.
From the side of laboratory indicators: often - an increase in ALT, ACT, alkaline phosphatase, an increase in the number of platelets; 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 glucose levels in the blood, a decrease in the number of segmented neutrophils and leukocytes, a decrease in hematocrit, hemoglobin and platelet count; bacteriuria, an increase in the level of serum urea nitrogen, the number of epithelial cells in the urine, the number of red blood cells in the urine.
Others: rarely - allergic reactions, general malaise, fungal infections.

Contraindications for use

Hypersensitivity to ertapenem or other antibiotics of the same group;
- Hypersensitivity to other beta-lactam antibiotics.

Use during pregnancy and lactation

Sufficient clinical experience Ertapemen has not been used during pregnancy. Ertapenem has been found to be excreted in human breast milk.
Use during pregnancy and lactation ( breastfeeding) is possible only in cases where the intended benefit of therapy for the mother justifies the potential risk to the fetus or infant.

Application for violations of kidney function

In patients with CC> 30 ml / min / 1.73 m 2, correction of the dosing regimen is not required. In patients with severe renal impairment (CC≤30 ml / min / 1.73 m 2), including those on hemodialysis, the recommended dose is 500 mg / day.

Use in children

Because The safety and efficacy of ertapenem in pediatrics have not been studied and its use in children and adolescents under 18 years of age is not recommended.

special instructions

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-lactam antibiotics). Before starting the use of ertapenem, a history of indications of previous hypersensitivity reactions to other allergens (especially penicillins, cephalosporins and other beta-lactam antibiotics) should be clarified.
When allergic reaction ertapenem should be discontinued immediately.
When using ertapenem (like many antibacterial agents) may develop pseudomembranous colitis (the main cause of which is a toxin produced by Clostridium difficile), which should be borne in mind if severe diarrhea occurs in patients receiving antibiotic therapy.
When administered intramuscularly, avoid accidental penetration of ertapenem into blood vessel.

Pediatric use

Because The safety and efficacy of ertapenem in pediatrics have not been studied and its use in children and adolescents under 18 years of age is not recommended.

drug interaction

Ertapenem does not affect drug metabolism mediated by the main isoenzymes CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. Interaction with drugs due to inhibition of tubular secretion, impaired binding to P-glycoprotein, or a change in the intensity of microsomal oxidation is unlikely.

Instructions for medical use drug

Description of the pharmacological action

Indications for use

Treatment of severe and moderate infectious and inflammatory diseases caused by susceptible strains of microorganisms (including for initial empirical antibiotic therapy until pathogens are identified):
- infections of the abdominal organs;
- 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.

Release form

lyophilisate for solution for injection 1 g; bottle (bottle) 20 ml, carton pack 1;

Compound
Lyophilisate for solution for injection 1 vial.
composition component 1.213 g
(corresponds to 1 g of ertapenem)
excipients: sodium bicarbonate; sodium hydroxide (up to pH 7.5); the sodium content is approximately 137 mg (6 mEq)
in glass bottles of 20 ml; in a pack of cardboard 1 bottle.

Pharmacodynamics

A beta-lactam antibiotic whose bactericidal activity is due to inhibition of cell wall synthesis and is mediated by its binding to penicillin-binding proteins (PSBs). In Escherichia coli, it exhibits strong affinity for PBP 1 alpha, 1 beta, 2, 3, 4 and 5, with a preference for PBP 2 and 3. Ertapenem has significant resistance to hydrolysis by beta-lactamases of most classes, including penicillinases, cephalosporinases and beta- extended spectrum lactamases, but not metallo-beta-lactamases. Active against most strains of the following microorganisms: aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus aureus (including penicillinase-producing strains; methicillin-resistant staphylococci are resistant), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes; aerobic and facultative anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including beta-lactamase producing strains), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis; anaerobic microorganisms: Bacteroides fragilis and other species of the Bacteroides group, Clostridium spp. (except Clostridium difficile), Eubacter spp., Peptostreptococcus spp., Porphyromonas asaccharolytica, Prevotella spp. The clinical significance of the following data on MIC values ​​obtained in vitro is unknown: when MIC is less than 2 μg / ml, it is active against most (more than 90%) strains of microorganisms of the genus Streptococcus, including Streptococcus pneumoniae, at a concentration of less than 4 μg / ml - against the majority (more than 90%) strains of Haemophilus spp. and at a concentration of less than 4 μg / ml - against the majority (more than 90%) of aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus spp., coagulase-negative methicillin-sensitive (methicillin-resistant staphylococci are resistant), Streptococcus pneumoniae (penicillin-resistant), Streptococci viridans. Many strains of microorganisms with multi-resistance to other antibiotics, such as penicillins, cephalosporins (including III generation) and aminoglycosides, are sensitive to the drug: aerobic and facultative anaerobic gram-negative microorganisms; anaerobic microorganisms - Fusobacterium spp. Resistant are many strains of Enterococcus faecalis and most strains of Enterococcus faecium, methicillin-resistant staphylococci.

Use during pregnancy

There is no sufficient clinical experience with the use of Invanz during pregnancy. The appointment of the drug is possible only in cases where the intended benefit of therapy for the mother justifies the potential risk to the fetus.

With caution, the drug is prescribed during lactation (breastfeeding), because. ertapenem is excreted in breast milk.

Contraindications for use

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

Hypersensitivity to other beta-lactam antibiotics.

When using intramuscular lidocaine hydrochloride as a solvent, the administration of the drug is contraindicated in patients with established hypersensitivity to local amide anesthetics, patients with severe arterial hypotension or impaired intracardiac conduction.

Side effects

Most of the adverse events reported in clinical trials were described as mild or moderate in severity. Due to adverse events that could presumably be associated with the drug, ertapenem was canceled in 1.3% of patients.

The most common adverse events associated with parenteral administration of the drug included diarrhea (4.3%), local complications after intravenous administration (3.9%), nausea (2.9%) and headache (2.1%) .

With parenteral administration of ertapenem, the following adverse events associated with the use of the drug have been reported. The following criteria for assessing the frequency of occurrence of adverse events were used: often - 1%; rarely - 0.1%.

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 of acidic contents, pseudomembranous colitis (often manifested by diarrhea) caused by uncontrolled reproduction of Clostridium difficile, dry mouth, dyspepsia, anorexia.

From the side of the cardiovascular system: rarely - a decrease in blood pressure.

From the respiratory system: rarely - dyspnea.

Dermatological reactions: rarely - erythema, itching.

On the part of the body as a whole: rarely - abdominal pain, taste perversion, weakness / fatigue, candidiasis, swelling, fever, chest pain.

Local reactions: often - post-infusion phlebitis / thrombophlebitis.

From the genital organs: vaginal itching.

On the part of laboratory parameters: often - an increase in ALT, ACT, alkaline phosphatase, an increase in the number of platelets; 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 glucose levels in the blood, a decrease in the number of segmented neutrophils and leukocytes, a decrease in hematocrit, hemoglobin and platelet count; bacteriuria, an increase in the level of serum urea nitrogen, the number of epithelial cells in the urine, the number of red blood cells in the urine.

In most clinical studies, parenteral therapy preceded the transition to the appropriate oral antimicrobial drug. During the entire period of treatment and within 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 (from 0.1 to 1%).

Dosage and administration

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. With intravenous administration, the duration of the infusion 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. In the presence of clinical indications, a transition to subsequent adequate oral antibiotic therapy is acceptable.

The drug can be used to treat infections in patients with renal insufficiency. In patients with CC> 30 ml / min / 1.73 m2, correction of the dosing regimen is not required. In patients with severe renal impairment (CC≤30 ml / min / 1.73 m2), including patients on hemodialysis, the recommended dose is 500 mg / day. There are no data on the use of the drug in children with renal insufficiency.

Adult patients on hemodialysis and who received the drug at a dose of 500 mg / day in the next 6 hours before a hemodialysis session, an additional 150 mg of the drug should be administered after the session. If the drug is administered more than 6 hours before hemodialysis, no additional dose is required. There are currently insufficient data to recommend to patients on peritoneal dialysis or hemofiltration. There are no data on the use of the drug in children on hemodialysis.

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 \u003d 0.85 x (value calculated for men)

In patients with impaired liver function, dose adjustment is not required. The recommended dose can be administered regardless of age and sex.

Rules for the preparation of solutions for parenteral administration

Adults and teenagers aged 13 and over

Reconstitute the lyophilisate by adding to the contents of 1 vial 10 ml of one of the following solvents: water for injection, 0.9% sodium chloride solution for injection or bacteriostatic water for injection. The vial should be shaken well and immediately add the reconstituted solution from the vial to the prepared 50 ml of 0.9% sodium chloride solution for infusion. The infusion must be performed within 6 hours after reconstitution of the lyophilisate.

To prepare a solution for injection, 3.2 ml of a 1% or 2% solution of lidocaine hydrochloride for injection (without epinephrine) is added to the contents of the vial (1 g), then the vial should be shaken 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, in the gluteal muscles or in the lateral muscles of the thigh). The prepared solution for intramuscular injection should be used within 1 hour.

Children aged 3 months to 12 years

Preparation of a solution for intravenous infusion

Do not mix or administer with other medicinal products. Do not use diluents containing dextrose (glucose).

Before administration, the lyophilisate must be reconstituted and then diluted.

Reconstitute the lyophilisate by adding to the contents of 1 vial 10 ml of one of the following solvents: water for injection, 0.9% sodium chloride solution for injection or bacteriostatic water for injection. The vial 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 must be performed within 6 hours after reconstitution of the lyophilisate.

Preparation of solution for intramuscular injection

The lyophilizate must be dissolved before administration.

To prepare a solution for injection, 3.2 ml of a 1% or 2% solution of lidocaine hydrochloride for injection (without epinephrine) is added to the contents of the vial (1 g), then the vial should be shaken well to dissolve the contents. Immediately, a volume equivalent to 15 mg/kg body weight (but not more than 1 g/day) should be withdrawn and injected deep into a large muscle (eg, gluteal muscles or lateral thigh muscles). The prepared solution for intramuscular injection should be used within 1 hour.

The reconstituted solution for intramuscular injection should not be used for intravenous infusion.

Parenteral medicinal products should be carefully inspected for particulate matter or discoloration prior to 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, accidental administration of the drug at a dose of up to 3 g / day did not lead to clinically significant adverse events.

Treatment: the drug should be discontinued and general maintenance therapy should be carried out (until ertapenem is completely eliminated from the body). The drug can be removed from the body by hemodialysis, but information on the use of hemodialysis for the treatment of overdose is not available.

Interactions with other drugs

When prescribing ertapenem together with drugs that block tubular secretion, adjustment of the dosing regimen is not required.

Ertapenem does not affect drug metabolism mediated by the main cytochrome P450 isoenzymes - 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.

No special clinical studies have been conducted on the interaction of ertapenem with specific drugs other than probenecid.

Special instructions for admission

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-lactam antibiotics). Before starting treatment with Invanz, the patient should be carefully asked about previous hypersensitivity reactions to other allergens (especially penicillins, cephalosporins and other beta-lactam antibiotics).

If an allergic reaction occurs, Invanz® should be discontinued immediately. Serious anaphylactic reactions require emergency treatment.

Prolonged use of Invanza, as with other antibiotics, may lead to overgrowth of non-susceptible organisms. With the development of superinfection, 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. Consideration should be given to the possibility of developing such a complication in the event of severe diarrhea in patients receiving antibiotic therapy.

With intramuscular administration, care should be taken to avoid accidental injection of the drug into a blood vessel.

In clinical studies, the efficacy and safety of the drug in the elderly (over 65 years) were comparable to those in younger patients.

Pediatric use

The appointment of the drug to persons under the age of 18 is not recommended, because. the safety and efficacy of its use in children has not been studied.

The reconstituted solution for infusion, immediately diluted in 0.9% sodium chloride solution, can be stored at room temperature(not above 25°C) and use within 6 hours or store within 24 hours in the refrigerator (5°C) and use within 4 hours of 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.

Storage conditions

At a temperature not higher than 25 °C.

Shelf life

Belonging to ATX-classification:

** The Medication Guide is for informational purposes only. For more complete information please refer to the manufacturer's instructions. Do not self-medicate; Before you start taking Invanz, you should talk to your doctor. EUROLAB is not responsible for the consequences caused by the use of the information posted on the portal. Any information on the site does not replace the advice of a doctor and cannot serve as a guarantee positive effect medicinal product.

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Included in medications

VED

J.01.D.H Carbapenems

J.01.D.H.03 Ertapenem

I.A30-A49.A40 Streptococcal septicemia

I.A30-A49.A41 Other septicemia

X.J10-J18.J15 Bacterial pneumonia, not elsewhere classified

X.J40-J47.J42 Chronical bronchitis unspecified

X.J20-J22.J20 Acute bronchitis

XI.K65-K67.K65.0 Acute peritonitis

XI.K80-K87.K81.0 Acute cholecystitis

XI.K80-K87.K81.1 Chronic cholecystitis

XI.K80-K87.K83.0 Cholangitis

XII.L00-L08.L01 Impetigo

XII.L00-L08.L02 Skin abscess, furuncle and carbuncle

XII.L00-L08.L03 Phlegmon

XII.L00-L08.L08.0 Pyoderma

XIII.M00-M03.M00 Pyogenic arthritis

XIII.M86-M90.M86 Osteomyelitis

XIV.N10-N16.N11.9 Chronic tubulointerstitial nephritis, unspecified

XIV.N10-N16.N10 Acute tubulointerstitial nephritis

XIV.N10-N16.N15.1 Abscess of the kidney and perirenal tissue

XIV.N30-N39.N30 Cystitis

XIV.N30-N39.N34 Urethritis and urethral syndrome

XIV.N40-N51.N41 Inflammatory diseases of the prostate

XIV.N70-N77.N70 Salpingitis and oophoritis

XIV.N70-N77.N71 Inflammatory diseases of the uterus, except for the cervix

XXI.Z20-Z29.Z29.2 Another type of prophylactic chemotherapy

pharmachologic effect
Pharmacodynamics
The drug belongs medicines group of antibiotics of the beta-lactam series. The active substance is ertapenem. Its therapeutic effect is due to the inhibition of cell membrane synthesis due to binding to penicillin-binding proteins (PSBs). For example, in Escherichia coli, it exhibits a pronounced affinity for PBP 1-α, 1-β, 2, 3, 4, and 5. The binding occurs predominantly with PBP 2 and 3.
Invanz has a significant resistance to most beta-lactamases, excluding drugs of the metallo-betalactamase group.
It is active against the vast majority of strains of aerobic and most facultative aerobic gram-positive bacteria, aerobic and facultative anaerobic gram-negative organisms, a large number of strains of anaerobic pathogens.
The drug is active against most strains of bacteria of the genus Streptococcus at an MIC less than 2 μg / ml, at a concentration of less than 4 μg / ml, Invanz is active against > 90% of strains of the bacterium Haemophilus spp. With the introduction of a similar concentration, Invanz is active against the vast majority of gram-positive bacteria, both aerobic and facultative anaerobic.
The drug has an effective effect on a large number of microorganisms resistant to other antibiotic drugs such as penicillins, aminoglycosides and cephalosporins (including third generation cephalosporins).
Most strains of Enterococcus faecalis bacteria, methicillin-resistant staphylococci and strains of Enterococcus faecalis bacteria are resistant to Invanz.

Pharmacokinetics
Invanz, reconstituted with 1% or 2% lidocaine solution, is well absorbed after intramuscular injection at the recommended dosage. Its bioavailability reaches 92%. The maximum concentration of Invanza with intramuscular injection is observed after about one and a half to two hours.
Invanz binds well to plasma proteins (its chemical bond with plasma proteins decreases in direct proportion to its concentration in the blood. At a concentration of 00 μg / ml, it is about 95%, while at a concentration of 300 μg / ml it is 85%).
Clinical studies have shown that the concentration of active active ingredient Invanza (ertapenem) in the breast milk of women during breastfeeding (measurement was carried out in five experimental subjects for 5 days at different time intervals from the time of infusion of the drug) was<0.38 мкг/мл в последний день терапии. К пятому дню после окончания терапии концентрация препарата в крови была неопределима у четырех испытуемых из пяти (у одной женщины определялись следовые количества Инванза (<0.13 мкг/мл).
The drug does not inhibit the transport of drugs due to P-glycoprotein (vinblastine, digoxin) and does not itself belong to the substrates of this transport.
Invanz is mainly excreted from the body by the kidneys. The half-life of the drug in healthy adults is about four hours. About 80% of Invanza is excreted in the urine, 10% in the feces. Of the 80% excreted in the urine, approximately 38% is excreted unchanged and 37% is modified.
In studies of young healthy subjects who were given a single infusion dose of one gram of the drug, the average concentration of the active substance in the urine for up to 2 hours after infusion exceeded 984 μg / ml, and within 12 hours after infusion to a day, it exceeded 52 mcg/ml.
Changes in pharmacokinetics depending on gender, age and individual characteristics
The concentration of the active ingredient of the drug (ertapenem) in men and women does not differ significantly.
When Invanz was administered to elderly patients (65 years of age or older), plasma concentrations of Invanz after standard dose infusion were not significantly higher than in younger subjects. Individual dose adjustment for elderly patients was not required.
The pharmacokinetics of Invanza in the case of administration of the drug to children has not been studied.
It should be noted that the pharmacokinetics of Invanza in patients with hepatic insufficiency has not been studied in sufficient detail. Given the insignificance of the intensity of its metabolism produced in the liver, it can be assumed that its dysfunction should not affect the pharmacokinetics in any way, and, therefore, dose adjustment is inappropriate for patients with liver failure.
In experimental subjects suffering from mild renal insufficiency (with creatinine clearance Сlcr 60-90 ml / min / 1.73 m2), the pharmacokinetics after a single infusion of a standard dose of 1 g did not differ from that in other patients without renal pathologies.
In the case of experimental subjects suffering from moderate renal insufficiency (with a creatinine clearance of 31-59 ml / min / 1.73 m2), the elimination half-life was increased by about 1.5 times compared with healthy patients.
In the case of subjects suffering from severe renal insufficiency (creatinine clearance 5-30 ml / min / 1.73 m2), the half-life compared with healthy subjects was increased by approximately 2.6 times.
In the case of test subjects suffering from end-stage renal failure (with creatinine clearance< 10 мл/мин/1.73 м2), период полувыведения был увеличен примерно в 2,9 раз. После единоразовой внутривенной инфузии стандартной дозы Инванза в 1 г незадолго до гемодиализа, примерно 30% введенного активного вещества определялось в полученном диализате.
In connection with the above, it is recommended to carry out an individual correction of the dosage of the drug in the case of antibiotic therapy in patients suffering from impaired renal function in severe and terminal stages.

Indications for use
Invanz is used for the treatment of adult patients suffering from moderate and severe infectious diseases caused by strains of microorganisms sensitive to the drug. The drug is also suitable for initial empiric therapy, pending the results of bacterial analysis. In this case, Invanz is indicated in the treatment of the following infectious pathologies:
- infections of the digestive tract;
- infectious lesions of the skin and subcutaneous adipose tissue, including diseases in diabetes ("diabetic foot");
- treatment of community-acquired pneumonia;
- bacterial septicemia;
- treatment of pyelonephritis and other infectious diseases of the urinary system;
- acute infectious diseases of the small pelvis, including postpartum endomyometritis, cases of septic abortion and postoperative gynecological infections.

Mode of application
The standard daily dosage of Invanz, prescribed to patients over 12 years of age, is 1 gram. The drug is taken once a day.
The drug can be taken as an intravenous infusion, as well as in the form of an intramuscular injection. In the case of intravenous drip infusion, the duration should not be less than half an hour.
Intramuscular injections are used if necessary, as an alternative to drip infusion.
The duration of the drug course is usually from three days to two weeks (depending on the infectious etiology of the microorganism that caused the disease). If the general condition improves during treatment, a transition to further oral antimicrobial therapy is possible.
It is necessary to remember about the need to adjust the daily dose of Invanz for patients with impaired renal filtration. For patients with creatinine clearance reaching more than 30 ml / min / 1.73 m2, individual dosage adjustment is not required. For those patients whose clearance is 30 ml / min / 1.73 m2 or less (including patients receiving hemodialysis procedures), a daily dose of 500 mg is prescribed.
Additionally, if the patient is on hemodialysis and the recommended dose of 500 mg was taken within 6 hours before the procedure, then after hemodialysis, another 150 mg of Invanz should be administered in addition to the main infusion. If the drug was administered 6 hours or more before the procedure, then an additional dose is not required. Regarding peritoneal dialysis or hemofiltration and their effect on the percentage of the administered drug in the blood, there are currently no exact data.
Patients with impaired hepatic function do not require individual dose adjustment.
The recommended dose of Invanza does not depend on the age of the adult patient or gender.

Solution preparation: instruction
Instructions for preparing the infusion solution:
Do not mix or inject simultaneously with other substances. Do not use liquids containing dextrose (a-d-glucose) as a diluting agent.
1) Reconstitute the contents of the vial by adding 10 ml of one of the solvents described below: saline for injection, water for injection or bacteriostatic water for injection.
2) Thoroughly shake the contents of the vial to dissolve completely, then add the solution from the Invanz vial to the prepared 50 ml saline solution for infusion.
3) Remember that the infusion should be carried out no later than six hours after the restoration of the drug.

Instructions for preparing a solution for intramuscular injection:
1) Dissolve the dry contents of one sealed vial in 3.2 ml of a 1% or 2% lidocaine solution. Shake the contents of the vial thoroughly to dissolve completely.
2) Draw the solution into the syringe and inject it following the standard rules for intramuscular injection. It is recommended to inject the drug deep into a large muscle mass.
3) The solution for intramuscular injection must be used within sixty minutes of preparation.
It is strictly forbidden to use a solution prepared for intramuscular injection for other purposes, including for intravenous infusion.
Before use, the Invas solution must be carefully examined for the presence of small particles or deviations from the normal color. The standard solution of the drug should be in the range from colorless to pale yellow (variations in the color of the solution within these limits do not affect the effectiveness of the drug).

Side effects
In the course of the studies, most of the identified side effects of the drug were either mild or moderate. Discontinuation of the drug in patients, presumably related to taking the drug, was observed in 1.3% of cases.
The most common manifestations of parenteral administration of Invaz were: diarrhea, local venous complications associated with infusions, nausea and headache. Rarely were diarrhea and vomiting.
Most side effects are rare.
On the part of the nervous system, these are: varying degrees of dizziness, sleep disturbances in the form of insomnia or daytime sleepiness, minor convulsions and quickly passing confusion.
On the part of the cardiovascular system, a decrease in blood pressure was observed.
Among the side effects on the respiratory system, rare cases of dyspnea were noted.
From the gastrointestinal tract were observed: candidiasis of the oral mucosa, belching, anorexia, dyspeptic disorders, constipation, pseudomembranous colitis.
From the skin and subcutaneous tissue: erythematous rash, itching.
Among the common adverse reactions were noted: pain in the abdomen, taste distortion, general slight weakness, swelling, pain in the chest, fever, increased fatigue.
In most studies, infusion and injection therapy preceded the change of the drug to adequate oral therapy. During the entire course of therapy and 14 days of observation of patients after its completion, side effects associated with the appointment of Invaz also included vaginitis and various types of rash, as well as various allergic reactions and fungal infections.
There have been reports of very serious (up to fatal cases) reactions of the anaphylactic type in patients treated with antibiotics of the beta-lactam group. Such reactions were more typical for patients with a history of polyvalent allergies. Before starting therapy, the doctor must make sure that the patient does not have a hypersensitivity reaction to other allergens, including cephalosporins, penicillins and other beta-lactam drugs.
If the first signs of an allergy to Invanz occur, the drug should be discontinued. Severe cases of hypersensitivity require immediate treatment.
Invanz also causes some changes in laboratory tests. The most common abnormalities are elevated levels of alkaline phosphatase, ALT, AST, and platelet counts. Among other, more rare deviations of analyzes during the course of Invaz therapy, the following are noted: an increase in the level of bilirubin (direct, indirect and total), the number of monocytes and eosinophils, creatinine and glucose, an increase in partial thromboplastin time. Taking Invas causes a decrease in the level of segmented neutrophils, a decrease in hemoglobin, platelets and hematocrit. There is an increase in serum urea nitrogen, epithelial cells and erythrocytes in the urine: the number of bacteria in the urine also increases.

Contraindications
The drug is categorically contraindicated for patients with a history of individual hypersensitivity to its active components or medicinal substances of the same series. Invanz is also not prescribed for patients with a history of allergic reactions to other beta-lactam antibiotics.
In the case of using lidocaine as a solvent, intramuscular injections are contraindicated in patients with existing hypersensitivity to local anesthetics of the amide group and in patients suffering from severe arterial hypotension or any intracardiac conduction disturbances.
It is not recommended to use Invanz for the treatment of patients under 18 years of age, since the safety of the drug in children has not been studied.

Pregnancy
Sufficient clinical studies on the use of Invanz in pregnancy are not available. The drug is recommended for use during pregnancy only if the potential danger to the fetus is justified by the possible benefits of therapy.
It must be remembered that Invanz tends to be secreted with milk. In the case of prescribing the drug to women during lactation, patients should be especially careful.

drug interaction
When prescribing Invanz simultaneously with drugs that have the property of blocking the secretion of the tubules, no individual adjustment of the dosage of the drug is required.
Invanz does not affect the metabolism of xenobiotic drugs, carried out through the main forms of cytochrome P450 (CYP) - 1A2, 2C9, 2C19, 2D6, 2E1 and ZA4. Also, drug interactions due to inhibition of renal tubular secretion, impaired formation of a chemical bond with P-glycoprotein, or modification of the intensity of microsomal oxidation are unlikely.
There have been no special studies of the interaction of Invaz with individual drugs, except for probenecid.

Overdose
Reliable information on the treatment of cases of drug overdose is not available. During clinical trials, administered daily dosages up to 3 g did not cause any significant side effects in patients.
In case of an overdose of Invanz, the drug should be discontinued, and a general treatment aimed at maintaining the body should be prescribed until the drug is eliminated from the body by the kidneys.
Also, if necessary, Invanz can be eliminated from the patient's body using hemodialysis. However, it should be mentioned that there is no reliable information on the use of hemodialysis in cases of drug overdose.

Release form
Glass vials, 20 ml capacity, sealed with a rubber stopper and crimped with an aluminum cap.
Each vial is packed in a separate cardboard box, accompanied by instructions for use.

Storage conditions
Stoppered vials with unreconstituted contents are stored at room temperature out of the reach of children.
The reconstituted infusion solution can be stored at room temperature for up to six hours, or up to a day if the reconstituted solution is stored in a refrigerator at 5 degrees Celsius. In the case of storage in the refrigerator, the solution is suitable for use not exceeding a time period of 3-4 hours after its extraction.
The prepared solution of Invanz is strictly forbidden to freeze.
The reconstituted solution for intramuscular injection is stored ready-made for no more than an hour.

Compound
One vial of Invanza contains 1.213 g of ertapenem sodium, which is equal to 1 gram of free form ertapenem. As excipients, one vial contains 203 mg of sodium bicarbonate and sodium hydroxide in the amount necessary to bring the pH to 7.5. The amount of sodium in the vial is approximately 137 mg (corresponding to 6 mEq).

Active substance:
Ertapenem

Additionally
Long-term therapy with drugs, as well as with other antibiotics, can cause the emergence of strains that are insensitive to Invanz. In case of development of superinfection during treatment, urgent measures must be taken.
When taking a course of antibiotic therapy, including ertapenem, there is a chance of pseudomembranous colitis of varying severity. This possibility should be considered for patients presenting with diarrhea following antibiotic administration. Clinical observations show that such cases are the result of the action of toxins produced by Clostridium difficile.
In the case of an intramuscular injection of Invanz, special care must be taken not to accidentally damage the blood vessel with the needle. You also need to remember that with intravenous administration of the drug, the solvent is lidocaine hydrochloride. Check with your doctor for details on how to use intramuscular lidocaine.
The drug is released only on prescription.

Ertapenem INN

International name: Ertapenem

Dosage form: lyophilisate for solution for injection

Chemical Name:

1 - beta methyl - carbapenem

Pharmachologic effect:

A beta-lactam antibiotic whose bactericidal activity is due to inhibition of cell wall synthesis and is mediated by its binding to penicillin-binding proteins (PSBs). In Escherichia coli, it exhibits strong affinity for PBP 1 alpha, 1 beta, 2, 3, 4 and 5, with a preference for PBP 2 and 3. Ertapenem has significant resistance to hydrolysis by beta-lactamases of most classes, including penicillinases, cephalosporinases and beta- extended spectrum lactamases, but not metallo-beta-lactamases. Active against most strains of the following microorganisms: aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus aureus (including penicillinase-producing strains; methicillin-resistant staphylococci are resistant), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes; aerobic and facultative anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including beta-lactamase producing strains), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis; anaerobic microorganisms: Bacteroides fragilis and other species of the Bacteroides group, Clostridium spp. (except Clostridium difficile), Eubacter spp., Peptostreptococcus spp., Porphyromonas asaccharolytica, Prevotella spp. The clinical significance of the following data on MIC values ​​obtained in vitro is unknown: when MIC is less than 2 μg / ml, it is active against most (more than 90%) strains of microorganisms of the genus Streptococcus, including Streptococcus pneumoniae, at a concentration of less than 4 μg / ml - against the majority (more than 90%) strains of Haemophilus spp. and at a concentration of less than 4 μg / ml - against the majority (more than 90%) of aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus spp., coagulase-negative methicillin-sensitive (methicillin-resistant staphylococci are resistant), Streptococcus pneumoniae (penicillin-resistant), Streptococci viridans. Many strains of microorganisms with multi-resistance to other antibiotics, such as penicillins, cephalosporins (including III generation) and aminoglycosides, are sensitive to the drug: aerobic and facultative anaerobic gram-negative microorganisms; anaerobic microorganisms - Fusobacterium spp. Resistant are many strains of Enterococcus faecalis and most strains of Enterococcus faecium, methicillin-resistant staphylococci.

Pharmacokinetics:

Well absorbed after i / m administration. Bioavailability - 92%. After the / m administration of 1 g / day TCmax - 2 hours. Actively binds to plasma proteins; the relationship decreases as its plasma concentration increases: from about 95% at a concentration of less than 100 μg / ml and up to 85% at a concentration of 300 μg / ml. In the dose range from 0.5 to 2 g, AUC increases almost in direct proportion to the dose. After repeated intravenous administration of doses in the range from 0.5 to 2 g per day or intramuscular injection of 1 g per day, cumulation is not observed. The concentration of ertapenem in the breast milk of lactating women after the last intravenous administration of 1 g is less than 0.38 mcg / ml on the last day of treatment (5-14 days after delivery), by day 5 after stopping treatment it is not detected or is determined in trace amounts (less than 0.13 μg/ml). About 6% is metabolized by hydrolysis of the beta-lactam ring to form an inactive metabolite (with an open ring). About 80% of the drug is excreted in the urine (38% - unchanged, about 37% - in the form of a metabolite), 10% - with faeces. T1 / 2 - 4 hours. The concentration of ertapenem in elderly patients after an intravenous dose of 1 and 2 g is slightly higher (approximately 39 and 22%, respectively) than in younger patients. The pharmacokinetics of ertapenem in children and in patients with hepatic impairment has 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. After a single intravenous injection of 1 g of ertapenem, AUC in patients with mild chronic renal failure (CC 60-90 ml / min) does not change; with moderate chronic renal failure (CC 31-59 ml / min) increases by approximately 1.5 times; with severe chronic renal failure (CC 5-30 ml / min) increases by approximately 2.6 times; with end-stage renal failure (CC less than 10 ml / min), AUC increases by about 2.9 times. After a single intravenous administration of a single dose of 1 g of ertapenem immediately before a hemodialysis session, about 30% of the administered dose is determined in the dialysate.

Indications:

Severe and moderate infections caused by susceptible strains of microorganisms (including for starting empirical antibiotic therapy until the results of determining the sensitivity of bacterial pathogens are obtained): abdominal infections, infections of the skin and subcutaneous tissue (including infections of the lower extremities in diabetes mellitus ), community-acquired pneumonia, infections of the urinary system (including pyelonephritis), acute infections of the pelvic organs (including postpartum endometritis, septic abortion and postoperative infections), bacterial septicemia.

Contraindications:

Hypersensitivity (including to other beta-lactam antibiotics), children under 3 months of age. When using lidocaine hydrochloride as a solvent for intramuscular administration: hypersensitivity to amide local anesthetic drugs, severe arterial hypotension, impaired intracardiac conduction. With caution. Pregnancy, lactation.

Dosing regimen:

In / in infusion (within 30 minutes), in / m. The dose for adults and children over 13 years old is 1 g, the frequency of administration is 1 time per day. Children from 3 months to 12 years - 15 mg / kg, divided into 2 injections (but not more than 1 g / day). IM administration can be used as an alternative to IV infusion. The course of treatment is 3-14 days, depending on the severity of the disease and the type of pathogen. In the presence of clinical improvement, a transition to subsequent adequate oral antimicrobial therapy is acceptable. Patients with chronic renal failure: with CC more than 30 ml / min, correction of the dosing regimen is not required. With QC less than or equal to 30 ml / min, incl. patients on hemodialysis - 500 mg / day. Patients on hemodialysis with the introduction of a daily dose of 500 mg in the next 6 hours before a hemodialysis session, an additional 150 mg of the drug should be administered after it. If the drug is administered more than 6 hours before hemodialysis, no additional dose is required. Currently, there is insufficient data on the optimal dosing regimen in patients on peritoneal dialysis or hemofiltration. Patients with hepatic impairment do not require dose adjustment. Preparation of a solution for intravenous infusion: the contents of the vial are diluted with 10 ml of 0.9% NaCl solution or water for injection, shaken. The resulting solution from the vial is added to 50 ml of 0.9% NaCl solution. The drug should be administered within 6 hours after dilution. Preparation of a solution for intramuscular injection: the contents of the vial are dissolved in 3.2 ml of a 1-2% lidocaine solution, shaken until completely dissolved, after which the solution is immediately drawn into a syringe and injected deeply into the / m. The prepared solution for intramuscular injection should be used within 1 hour.

Side effects:

Frequent (1-10%): headache, post-infusion phlebitis/thrombophlebitis, diarrhea, nausea, vomiting. Rare (0.1-1%): dizziness, weakness/fatigue, drowsiness, insomnia, convulsions, confusion; decrease in blood pressure; dyspnea; candidiasis of the oral mucosa, pseudomembranous colitis caused by Clostridium difficile (often manifested by diarrhea), dry mouth, dyspepsia (including constipation, belching of sour contents), anorexia, abdominal pain, taste perversion; skin rash (including erythematous, urticaria), skin itching; vaginal candidiasis (vaginal itching), swelling, fever, chest pain. Allergic and anaphylactic reactions (more often in persons with a history of polyvalent allergies, including penicillin and other beta-lactam antibiotics), superinfection. Laboratory indicators: often - increased activity of ALT, ACT, alkaline phosphatase and thrombocytosis, less often - increased direct, indirect and total bilirubin, partial thromboplastin time, eosinophilia, monocytosis, hypercreatininemia and hyperglycemia; a decrease in the number of segmented neutrophils and leukopenia, a decrease in hematocrit and Hb, thrombocytopenia; bacteriuria, increased urea nitrogen in serum, epithelial cells in the urine, erythrocyturia. Overdose. Symptoms: accidental administration of up to 3 g / day did not lead to clinically significant adverse events. Treatment: withdrawal of the drug, maintenance. Hemodialysis is effective, but experience with its use in overdose is not available.

Special instructions:

It is possible to develop pseudomembranous colitis, the severity of which can vary from mild to life-threatening, so it is necessary to keep in mind the possibility of its development in patients with diarrhea. When administered intramuscularly, accidental injection into a blood vessel should be avoided.

Interaction:

Do not use solutions containing dextrose as a solvent. When co-administered with drugs that block tubular secretion, correction of the dosing regimen is not required. Does not affect the metabolism of xenobiotics, mediated by the six main isoenzymes of cytochrome P450: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Interaction with drugs due to inhibition of tubular secretion, impaired binding to P-glycoprotein, or changes in the intensity of microsomal oxidation is unlikely.