Invanz lyophilisate for preparation of solution for injection 1g, No. 1

Treatment of severe and moderate severity of infectious and inflammatory diseases caused by sensitive strains of microorganisms (including for starting empirical antibiotic therapy before identifying pathogens):

• 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.

Administered by intravenous infusion or intramuscular injection.

When administered intravenously, the duration of the infusion should be 30 minutes. IM administration can be an alternative to IV infusion. The average daily dose of the drug for adults is 1 g, the frequency of administration is 1 time / day. The usual duration of therapy is 3 to 14 days, depending on the severity of the disease and the type of microorganism.

In the presence of clinical indications, a transition to subsequent adequate oral antimicrobial therapy is permissible. In patients with CC> 30 ml / min / 1.73 m2, correction of the dosage regimen is not required. In patients with severe renal impairment (CC ? 30 ml / min / 1.73 m2), including those on hemodialysis, the recommended dose is 500 mg / day.

Patients on hemodialysis and who received ertapenem at a dose of 500 mg / day in the next 6 hours before the hemodialysis session should additionally receive 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.

Lyophilisate for preparation of solution for injection in the form of powder or porous mass of white or almost white color.

1 fl. ertapenem sodium 1.213 g,?

which corresponds to the content of ertapenem 1 g

Excipients: sodium bicarbonate - 203 mg, sodium hydroxide - up to pH 7.5.

• Hypersensitivity to ertapenem or other antibiotics of the same group;

• hypersensitivity to other beta-lactam antibiotics.

pharmachologic effect

An antibiotic from the carbapenem group, is 1-? methyl carbapenem, a long-acting beta-lactam antibiotic for parenteral administration. Possesses a wide spectrum of 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 a strong affinity for PSB 1a, 1b, 2, 3, 4 and 5, and preferably for PSB 2 and 3. Ertapenem has significant resistance to the action of ?-lactamases of most classes (including penicillinases, cephalosporinases, and ?-lactamases extended spectrum, but not metallo -? - lactamase).

Active against 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 strains producing ?-lactamase), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis.

It is active against 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 ?-lactamases), Haemophilus parainfluenzae, Klebsilebsiella oxyitoca? Morganella morgani, Proteus vulgaris, Serratia marcescens.

Many strains of the microorganisms listed above that have multi-resistance to other antibiotics, for example, penicillins, cephalosporins (including generation III) and aminoglycosides, are sensitive to ertapenem.

Active against anaerobic microorganisms Fusobacterium spp.

Pharmacokinetics

With i / m administration of a solution prepared with 1% or 2% lidocaine solution, 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 about 2 hours.

Ertapenem actively binds to human plasma proteins. The degree of binding decreases with increasing plasma concentration of ertapenem - from about 95% at a plasma concentration of <100 ?g / ml to about 85% at a plasma concentration of 300 ?g / ml).

AUC increases in almost direct proportion 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.

Ertapenem is excreted in human breast milk.

Ertapenem does not inhibit the transport of digoxin and vinblastine, mediated by P-glycoprotein, and itself is not its substrate.

After intravenous infusion of isotopically labeled ertapenem at a dose of 1 g, the source of radioactivity in plasma is mainly (94%) ertapenem. The main metabolite of ertapenem is an open-ring derivative formed by hydrolysis of the ?-lactam ring.

Ertapenem is excreted mainly by the kidneys. The mean T1 / 2 from plasma in healthy adult young volunteers is approximately 4 hours. After 1 g intravenous administration of isotope-labeled ertapenem to healthy young volunteers, about 80% of the tag is excreted in the urine and 10% in the feces. Of 80% of ertapenem determined in urine, about 38% is excreted unchanged, and about 37% is excreted as a metabolite with an open ?-lactam ring.

In healthy young adult volunteers who received ertapenem intravenously at a dose of 1 g, the average concentration of ertapenem in urine within 0-2 hours after the administration of this dose exceeds 984 ?g / ml, and within 12-24 hours - exceeds 52 ?g / ml ...

In patients with moderate renal insufficiency (CC 31-59 ml / min / 1.73 m2), AUC is approximately 1.5 times increased compared to healthy volunteers.

In patients with severe renal insufficiency (CC 5-30 ml / min / 1.73 m2), AUC is increased by approximately 2.6 times compared with healthy volunteers.

In patients with end-stage renal failure (CC <10 ml / min / 1.73 m2), the AUC is approximately 2.9 times higher than in healthy volunteers. After a single intravenous injection of ertapenem at a dose of 1 g immediately before a hemodialysis session, about 30% of the administered dose is determined in the dialysate.

Side effect

From the side of the central nervous system: often - headache; rarely - dizziness, drowsiness, insomnia, 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 - lowering blood pressure.

From the respiratory system: rarely - dyspnea.

Dermatological reactions: often - rash; rarely - erythema, itching.

From the side 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, the level of creatinine and glucose 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 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.

Application during pregnancy and lactation

There is no sufficient clinical experience with the use of ertapemen during pregnancy. It has been established that ertapenem is excreted in human breast milk.

Use during pregnancy and lactation (breastfeeding) is possible only in cases where the intended benefit of therapy to the mother justifies the potential risk to the fetus or infant.

Application for impaired renal function

In patients with CC> 30 ml / min / 1.73 m2, correction of the dosage regimen is not required. In patients with severe renal impairment (CC ? 30 ml / min / 1.73 m2), including those on hemodialysis, the recommended dose is 500 mg / day.

Application in children

Because the safety and efficacy of ertapenem in pediatrics has not been studied; its use in children and adolescents under the age of 18 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 people with a history of polyvalent allergies (in particular, people with a hypersensitivity to penicillin often develop severe hypersensitivity reactions when treated with other beta-lactam antibiotics). Before starting the use of ertapenem, it is necessary to clarify the history of indications of previous hypersensitivity reactions to other allergens (especially to penicillins, cephalosporins and other beta-lactam antibiotics).

If an allergic reaction occurs, ertapenem should be discontinued immediately.

With the use of ertapenem (like many antibacterial agents), pseudomembranous colitis may develop (the main cause of which is the 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 the blood vessel.

Use in pediatrics

Because the safety and efficacy of ertapenem in pediatrics has not been studied; its use in children and adolescents under the age of 18 is not recommended.

Drug interactions

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 changes in the intensity of microsomal oxidation is unlikely