Cepime, vials 1g

Composition

Powder for preparing a solution for intravenous and intramuscular use is white or white with a yellowish tinge of color, hygroscopic.

Auxiliary substances:

arginine – 0.72 g.

Solvent:

d/i water or 0.9% sodium chloride (amp. 5 ml).

Pharmacological action

Broad-spectrum antibacterial drug from the group of cephalosporins of the IV generation for injection. It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms. It has a broad spectrum of action against gram-positive and Gram-negative bacteria, including strains resistant to aminoglycosides and / or cephalosporin antibiotics of the third generation.

It is highly resistant to hydrolysis by most plasmid and chromosomal β-lactamases and quickly penetrates gram-negative bacterial cells. Inside the bacterial cell, the molecular target is penicillin-binding proteins.

Active in vivo and in vitro against gram-positive aerobes:  Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pneumoniae, Streptococcus pyogenes (Group A), Streptococcus viridans; gram-negative aerobes:  Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa.

In vitro active against gram-positive aerobes:  Staphylococcus epidermidis (methicillin-sensitive strains only), Staphylococcus saprophyticus, Streptococcus agalactiae (Group B); gram-negative aerobes:  Acinetobacter lwoffii, Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, Haemophilus influenzae (including beta-lactamase-producing strains), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (including beta-lactamase-producing strains), Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens.

Resistant to Cefepimee:  most strains of Enterococcus spp. Enterococcus faecalis), methicillin-resistant staphylococci, Stenotrophomonas maltophilia (formerly known as Xanthomonas maltophilia), Bacteroides fragilis, Clostridium difficile.

Pharmacokinetics

Suction

Bioavailability – 100%. TC_max after intravenous use of the drug at a dose of 0.5 g – by the end of the infusion. TC_max after the/m introduction in a dose of 0.5 g – 1-2 hours C_max with the/m introduction of the drug in doses of 0.5 g,1 g and 2 g – 14 µg/ml,30 µg/ml and 57 µg/ml, respectively; at/in the introduction to the doses of 0.25 g,0.5 g,1 g and 2 g – 18 µg/ml, and 39 mcg/ml,82 µg/ml and 164 µg/ml, respectively.

The time to reach the average therapeutic concentration in plasma is 12 hours; the average therapeutic concentration with intravenous use is 0.2 mcg / ml, with intravenous use-0.7 mcg/ml.

Distribution

High concentrations of Cefepimee are detected in the urine, bile, peritoneal fluid, exudate of the blister, mucosal secretions of the bronchi, sputum, prostate gland, appendix and gallbladder. Vd – 0.25 l / kg, in children from 2 months to 16 years-0.33 l / kg. Binding to plasma proteins is 20%. It is excreted in breast milk.

Metabolism

It is metabolized in the liver and kidneys by 15%.

Elimination

T_1/2 – 2 h, total clearance – 120 ml/min, renal clearance – 110 ml/min. Excreted by the kidneys, by glomerular filtration in unchanged form-85%. T_1/2 with hemodialysis – 13 hours, with continuous peritoneal dialysis-19 hours.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug: Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases associated with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae, or Enterobacter spp.. Febrile neutropenia (empirical therapy). Complicated and uncomplicated urinary tract infections (including pyelonephritis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis. Uncomplicated skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pyogenes. Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli. Klebsiella pneumoniae. Pseudomonas aeruginosa, Entcrobactcr spp.. Bacteroides fragilis. Prevention of infections during oral surgery.

Contraindications

Hypersensitivity to the components that make up the drug (including antibiotics cephalosporins, penicillins and other beta-lactam antibiotics); children under 2 months of age (for intravenous use) (safety and efficacy in children under 2 months have not been established); children under 12 years of age (for intramuscular use). With caution: Diseases of the gastrointestinal tract (including in the anamnesis): pseudomembranous colitis, ulcerative colitis, regional enteritis or antibiotic-associated colitis; chronic renal failure.

Side effects

Allergic reactions:  skin rash( including erythematous rashes), pruritus, fever, anaphylactoid reactions, eosinophilia, erythema multiforme (including Stevens-Johnson syndrome), rarely toxic epidermal necrolysis (Lyell’s syndrome).

Nervous system disorders:  headache, dizziness, insomnia, paresthesia, anxiety, confusion, convulsions, encephalopathy (in the absence of dose adjustment in patients with impaired renal function).

From the genitourinary system:  vaginitis.

From the urinary system:  impaired renal function.

From the gastrointestinal tract:  diarrhea, nausea, vomiting, constipation or diarrhea, abdominal pain, dyspepsia, pseudomembranous colitis.

Hematopoietic disorders: anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, hemolytic anemia, bleeding.

Respiratory system disorders: cough, chest pain.

From the cardiovascular system:  tachycardia, shortness of breath, peripheral edema. Laboratory parameters: decreased hematocrit, increased prothrombin time, increased urea concentration, hypercreatininemia, hyercalcemia, increased activity of “hepatic” transaminases and alkaline phosphatase, hyperbilirubinemia, positive Coombs test (without hemolysis).

Local reactions: with intravenous use – phlebitis, with intramuscular-hyperemia and soreness at the injection site.

Other services:  sore throat, thoracalgia, increased sweating, back pain, asthenia, development of superinfection, oropharyngeal candidiasis.

Interaction

Pharmacologically incompatible with other antimicrobial drugs and heparin. Diuretics, aminoglycosides, polymyxin B reduces the tubular secretion of Cefepimee and increases its concentration in the blood serum, lengthens T 1/2, increases nephrotoxicity (increases the risk of developing nephronskrosis). Cefepimee increases the ototoxicity of aminoglycosides. Nonsteroidal anti-inflammatory drugs, slowing the elimination of cephalosporins, increase the risk of bleeding. When administered concomitantly with bactericidal antibiotics (aminoglycosides), synergy is shown, with bacteriostatic (macrolides. chloramphenicol, tetracyclines) – antagonism. Incompatible with metronidazole solution (before use of metronidazole solution for the prevention of infections during surgical procedures, the infusion system should be flushed from Cefepimee solution). To avoid possible drug interactions with other drugs, Cefepimee solutions (like most other beta-lactam antibiotics) should not be administered simultaneously with solutions of vancomycin, gentamicin, tobramycin, netilmycin. When prescribing Cefepimee with these drugs, each antibiotic should be administered separately.

How to take, course of use and dosage

Assign IV (jet and drip) and less often-iv (only for complicated or uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli).

The dose and route of use of the drug vary depending on the sensitivity of pathogenic microorganisms, the severity of infection, and the state of renal function in the patient.

Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases associated with concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp. – iv 1-2 g every 12 hours for 10 days.

Febrile neutropenia (empirical therapy) – iv 2 g every 8 hours for 7 days or until neutropenia resolves.

Complicated or uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis-iv or iv (only for infections caused by Escherichia coli) 0.5-1 g every 12 hours for 7-10 days.

Severe complicated or uncomplicated urinary tract infections (including pyelonephritis) caused by Escherichia coli or Klebsiella pneumoniae – iv 2 g every 12 hours for 10 days.

Moderate to severe skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pyogenes – iv 2 g every 12 hours for 10 days.

Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis-iv 2 g every 12 hours for 7-10 days.

To prevent infection during surgical interventions on the abdominal organs-60 minutes before the start of surgery,2 g of the drug is administered intravenously for 30 minutes. At the end of the infusion,500 mg of metronidazole is additionally administered intravenously. Metronidazole solutions should not be administered simultaneously with Cefepimee. The infusion system should be flushed before use of metronidazole.

During long-term (more than 12 hours) surgical operations,12 hours after the first dose, repeated intravenous use of 2 g for 30 minutes is recommended, followed by the introduction of 500 mg of metronidazole.

In children aged 2 months to 16 years and weighing up to 40 kg, the recommended dosage regimen for all indications (excluding febrile neutropenia) is 50 mg/kg every 12 hours iv; in febrile neutropenia-50 mg / kg every 8 hours. The duration of treatment is the same as in adults (7-10 days).

In patients with impaired renal function (CC The initial dose of Cefepimee should be the same as for patients with normal renal function. Recommended maintenance doses of the drug are shown in the table.

Patients on hemodialysis are given 1 g on day 1, then 0.5 g every 24 hours for all infections and 1 g every 24 hours for the treatment of febrile neutropenia. On the day of hemodialysis, the drug is administered after the end of the hemodialysis session; it is advisable to enter Cefepimee every day at the same time.

Data on the use of the drug in children with concomitant chronic renal failure are not available, however, given the similarity of pharmacokinetics in children and adults, the dosage regimen (reducing the dose or increasing the interval between injections) in children with chronic renal failure is similar to the dosage regimen in adults.

Overdose

Symptoms (more common in patients with chronic renal failure): convulsions, encephalopathy, neuromuscular agitation. Treatment: hemodialysis and maintenance therapy.

Special instructions

Pseudomembranous colitis may occur when Cefepimee is used. Therefore, it is important to keep this diagnosis in mind if diarrhea occurs during treatment with the drug. Mild forms of colitis do not require special treatment, it is enough to stop the drug use; moderate or severe cases may require special treatment. Possible cross – hypersensitivity in patients with allergic reactions to penicillins. In case of combined severe renal and hepatic insufficiency, the plasma concentration of the drug should be regularly determined (dose adjustment is carried out depending on creatinine clearance). With long-term treatment, regular monitoring of peripheral blood, indicators of the functional state of the liver and kidneys is necessary. In case of mixed aerobic-anaerobic infection, a combination with drugs active against anaerobes is advisable before identifying the pathogens. Patients who have meningeal dissemination from a remote source of infection, are suspected of meningitis, or have a confirmed diagnosis of meningitis should be prescribed an alternative antibiotic with proven clinical efficacy in this situation. It is possible to detect a positive Coombs test, a false-positive test for glucose in the urine.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 30 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date.

Active ingredient

Cefepimee

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Indications

Gastrointestinal Infections, Skin Infections, Pneumonia