Ertam-AF (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Alpharma, LLC (Russia)

Manufactured By

Deko Company, LLC (Russia)

ATC Code

J01DH03 (Ertapenem)

Active Substance

Ertapenem (Rec.INN registered by WHO)

Dosage Form

Ertam-AF

Lyophilisate for preparation of solution for intramuscular administration and infusions 1 g: vial. 1 or 10 pcs.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intramuscular administration and infusions in the form of a powder or porous mass of white or almost white color; the ready solution is a clear liquid from colorless to pale yellow.

Excipients: sodium bicarbonate (E500), sodium hydroxide.

1 g – vials of colorless glass with a capacity of 20 ml (1) – cardboard packs.
1 g – vials of colorless glass with a capacity of 20 ml (10) – cardboard boxes.

Clinical-Pharmacological Group

Antibiotic of the carbapenem group

Pharmacotherapeutic Group

Systemic antibacterial agents; other beta-lactam antibacterial agents; carbapenems

Pharmacological Action

An antibiotic from the carbapenem group, it is a 1-β methyl-carbapenem, a long-acting beta-lactam antibiotic for parenteral administration. It has a broad spectrum of antibacterial 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 exhibits strong affinity for PBPs 1a, 1b, 2, 3, 4, and 5, with a preference for PBPs 2 and 3. Ertapenem is significantly resistant to the action of beta-lactamases of most classes (including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases, but not metallo-beta-lactamases).

Active against aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus aureus (including penicillinase-producing strains), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes.

Active against aerobic and facultative anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including beta-lactamase-producing strains), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis.

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.

Also active against aerobic and facultative anaerobic gram-negative microorganisms: Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli (producing extended-spectrum beta-lactamases), Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae (producing extended-spectrum beta-lactamases), Morganella morganii, Proteus vulgaris, Serratia marcescens.

Many strains of the microorganisms listed above, which are multi-resistant to other antibiotics, such as penicillins, cephalosporins (including III generation) and aminoglycosides, are susceptible to ertapenem.

Active against anaerobic microorganisms Fusobacterium spp.

Pharmacokinetics

When administered intramuscularly as a solution prepared with 1% or 2% lidocaine solution, Ertapenem is well absorbed from the injection site. The bioavailability is approximately 92%. After intramuscular administration of a 1 g dose, C_max is reached approximately after 2 hours.

Ertapenem actively binds to human plasma proteins. The degree of binding decreases as the plasma concentration of ertapenem increases – from approximately 95% at plasma concentrations <100 mcg/ml to approximately 85% at plasma concentrations of 300 mcg/ml.

AUC increases almost directly proportionally to the dose (in the dose range from 0.5 g to 2 g).

No accumulation of ertapenem is observed after multiple intravenous administrations (in the dose range from 0.5 to 2 g/day) or intramuscular administration of 1 g/day.

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 for it.

After an 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 beta-lactam ring.

Ertapenem is eliminated primarily by the kidneys. The mean plasma T_1/2 in healthy young adult 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 determined in the urine, about 38% is excreted unchanged, and about 37% as the open beta-lactam ring metabolite.

In healthy young adult volunteers who received Ertapenem intravenously at a dose of 1 g, the mean concentration of ertapenem in urine during 0-2 hours after administration of this dose exceeded 984 mcg/ml, and during 12-24 hours it exceeded 52 mcg/ml.

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

In patients with severe renal impairment (CrCl 5-30 ml/min/1.73 m²), AUC is increased approximately 2.6-fold compared to healthy volunteers.

In patients with end-stage renal disease (CrCl<10 ml/min/1.73 m²), AUC is increased approximately 2.9-fold 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 susceptible strains of microorganisms (including for initial empiric antibacterial therapy before identification of pathogens): intra-abdominal infections; skin and subcutaneous tissue infections, including lower limb infections in diabetes mellitus (“diabetic” foot); community-acquired pneumonia; urinary tract infections (including pyelonephritis); acute pelvic infections (including postpartum endomyometritis, septic abortion and postoperative gynecological infections); bacterial septicemia.

ICD codes

Dosage Regimen

It is administered by intravenous infusion or intramuscular injection. When administered intravenously, the infusion duration should be 30 minutes. Intramuscular administration can be an alternative to intravenous infusion.

The average daily dose of the drug for adults is 1 g, the frequency of administration is once daily.

The usual duration of therapy is from 3 to 14 days depending on the severity of the disease and the type of microorganisms. If clinically indicated, a switch to subsequent adequate oral antimicrobial therapy is permissible.

In patients with CrCl>30 ml/min/1.73 m², no dosage adjustment is required. In patients with severe renal impairment (CrCl≤30 ml/min/1.73 m²), including those on hemodialysis, the recommended dose is 500 mg/day.

Patients on hemodialysis who received Ertapenem at a dose of 500 mg/day within 6 hours before the hemodialysis session should be given 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.

Adverse Reactions

From the CNS often – headache; rarely – dizziness, drowsiness, insomnia, seizures, confusion.

From the digestive system often – diarrhea, nausea, vomiting; rarely – oral candidiasis, constipation, acid regurgitation, pseudomembranous colitis (often manifested by diarrhea), caused by uncontrolled proliferation of Clostridium difficile , dry mouth, dyspepsia, anorexia.

From the cardiovascular system rarely – decreased BP.

From the 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 genital organs: vaginal itching.

From laboratory parameters often – increased ALT, AST, ALP, increased platelet count; rarely – increased direct, indirect and total bilirubin, increased eosinophil and monocyte count, increased partial thromboplastin time, serum creatinine and blood glucose levels, decreased segmented neutrophil and leukocyte count, decreased hematocrit, hemoglobin and platelet count; bacteriuria, increased serum urea nitrogen level, epithelial cell count in urine, red blood cell count in urine.

Other rarely – allergic reactions, general malaise, fungal infections.

Contraindications

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

Use in Pregnancy and Lactation

There is insufficient clinical experience with the use of ertapenem 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 therapeutic benefit for the mother justifies the potential risk to the fetus or breastfed infant.

Use in Renal Impairment

In patients with CrCl>30 ml/min/1.73 m², no dosage adjustment is required. In patients with severe renal impairment (CrCl≤30 ml/min/1.73 m²), including those on hemodialysis, the recommended dose is 500 mg/day.

Pediatric Use

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

Special Precautions

Serious (including fatal) anaphylactic reactions have been reported in patients receiving treatment with beta-lactam antibiotics. These reactions are more likely in individuals with a history of polyvalent allergies (in particular, individuals with hypersensitivity to penicillin often develop severe hypersensitivity reactions when treated with other beta-lactam antibiotics). Before starting ertapenem, the presence of a history of previous hypersensitivity reactions to other allergens (especially penicillins, cephalosporins and other beta-lactam antibiotics) should be ascertained.

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

When using ertapenem (as with many antibacterial agents), the development of pseudomembranous colitis (the main cause of which is a toxin produced by Clostridium difficile) is possible, which should be considered if severe diarrhea occurs in patients receiving antibacterial therapy.

When administering intramuscularly, avoid accidental entry of ertapenem into a blood vessel.

Use in pediatrics

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

Drug Interactions

Ertapenem does not affect the metabolism of drugs mediated by the major CYP 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.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.