Cefepim, 1 g

Cefepim is an antibacterial agent of the IV generation of cephalosporins.

It acts bactericidally by disrupting synthesis of the cell wall of microorganisms.

It has a broad spectrum of action against Gram-positive and Gram-negative bacteria and strains resistant to aminoglycosides and/or 3rd generation cephalosporin antibiotics.

Highly resistant to hydrolysis of most beta-lactamases and quickly penetrates Gram-negative bacterial cells. Penicillin-binding proteins are the molecular target inside the bacterial cell.

It is active in vivo and in vitro against Gram-positive aerobes: Staphylococcus aureus (only methicillin-sensitive strains), Streptococcus pneumoniae, Streptococcus pyogenes (group A), Streptococcus group viridans; Gram-negative aerobes: Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa. In vitro active (but clinical significance is unknown) 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. Most strains of Enterococcus, including Enterococcus faecalis, methicillin-resistant staphylococci, Stenotrophomonas (formerly known as Xanthomonas maltophilia and Pseudomonas maltophilia), Clostridium difficile are not sensitive to cefepime.

Indications

Adults

The treatment of infections caused by susceptible strains of relevant microorganisms:

Pneumonia (moderate to severe) caused by Streptococcus pneumoniae, including cases with concurrent bacteremia, Pseudomonas aeruginosa, Klebsiella pneumonia or Enterobacter species;

Empirical therapy for patients with neutropenic fever. Cefepim as monotherapy is indicated for empirical treatment of patients with febrile neutropenia. In patients with a high risk of severe infection (including patients with a recent history of bone marrow transplantation (there is insufficient data to support the effectiveness of cefepime monotherapy in these patients; if necessary, combined therapy with antibiotics from the group of aminoglycosides or glycopeptides is recommended, taking into account the individual risk profile of the patient), hypotension, hematological malignancy, severe or prolonged neutropenia) – as part of combination therapy;

– Uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by Escherichia coli or Klebsiella pneumoniae, of any severity, as well as mild to moderately severe infections caused by Proteus mirabilis, including cases involving simultaneous bacteremia with these microorganisms;

– uncomplicated infections of the skin and its structures caused by Staphylococcus aureus (methicillin-sensitive strains only) or Streptococcus pyogenes;

– complicated intra-abdominal infections (in combination with metronidazole) caused by Echerichia coli, streptococci viridens, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species or Bacteroides fragilis.

Children

Infections caused by microorganisms sensitive to cefepime:

– bacteremia associated with, or suspected to be associated with, one of the infections mentioned;

– severe pneumonia;

– severe urinary tract infections;

– bacterial meningitis;

– empirical treatment of febrile episodes in patients with moderate (neutrophils < 1000/mm3) or severe (neutrophils ≤ 500/mm3) neutropenia. Antimicrobial monotherapy is not applicable in patients at high risk of serious infection (e.g., patients with a recent bone marrow transplant, low initial blood pressure, oncohematological disease, or severe or prolonged neutropenia). The available data on the efficacy of cefepime monotherapy in these patients are insufficient. If necessary, combination therapy with an aminoglycoside or glycopeptide antibiotic is recommended, taking into account the individual risk profile of the patient.

In order to reduce the development of drug-resistant bacteria and to maintain the efficacy of Cefepim and other antibacterial agents, the drug should be used only to treat infections that are caused by susceptible bacteria. When culture and susceptibility information is available, the drug should be used only for the treatment of infections caused by susceptible bacteria. In the absence of such data, epidemiologic data may contribute to the choice of empirical therapy.

Active ingredient

Composition

1 vial contains:

the active ingredient – cefepime -1 g (as cefepime hydrochloride and L-arginine).

How to take, the dosage

The doses and route of administration depend on the sensitivity of the pathogen, the severity of the infection, renal function, and the patient’s general condition.

The dosing recommendations for the medication are listed in Table 1.

Table 1. Dosing in patients with normal renal function

(creatinine clearance (CK) greater than 50 mL/min)

dosage recommendations/p>

Location and type of infection Dose Frequency Duration2 (days) Adults and children over 12 years of age (with a body weight greater than 40 kg) Adults and children over 12 years of age (with a body weight greater than 40 kg)/td> Moderate to severe pneumonia caused by S. pneumoniae*, P. aeruginosa1, K. pneumoniae, or Enterobacter spp. 1-2 g w/v Every 12 h 10 Empirical therapy for patients with febrile neutropenia 2 g w/v Every

8 h

pneumonia,

complicated urinary tract infections.

Serious infections: 50 mg/kg body weight every 8 hours

Serious infections: 30 mg/kg body weight every 8 hours

* Including cases involving concurrent bacteremia.

** Or until neutropenia ends. In patients with decreased fever but neutropenia for more than 7 days, the need for continued antibiotic therapy should be reconsidered.

*** The intramuscular route of administration is indicated only for mild to moderate uncomplicated or complicated urinary tract infections caused by E. coli.

1 In the treatment of pneumonia caused by P. aeruginosa: 2 g administered by IV every 8 hours.

2 The duration of treatment is usually 7 to 10 days. The maximum duration as a whole is at least 7 but not more than 14 days. Duration of empirical treatment of febrile neutropenia: from 7 days until neutropenia disappears.

The experience of use in children under 1 month of age is limited and is based on dose calculations based on experience with a dose of 50 mg/kg body weight derived from pharmacokinetic data in patients older than 1 month, which corresponds to a dose of 30 mg/kg body weight every 12 or 8 hours for children aged 1 to 2 months. Children of this age should be closely monitored during the administration of the drug.

In children with a body weight greater than 40 kg, the recommended dose is the same as for adults (see table). In children over 12 years of age with a body weight less than 40 kg, the recommended dose is the same as for children with a body weight ≤ 40 kg. The maximum dose in children should not exceed the maximum dose for adults (2.0 g every 8 hours).

The duration of treatment is usually 7 to 10 days. In general, cefepime is recommended for at least 7 but not more than 14 days.

In empirical treatment of febrile neutropenia the duration of treatment is usually up to 7 days or until the neutropenia ends.

Patients with impaired renal function. Cefepime is excreted by the kidneys by glomerular filtration, therefore in patients with impaired renal function (creatinine clearance (CK) less than 50 ml/min) the dose of Cefepime should be adjusted. In these patients, the recommended starting dose of cefepime should be the same as in patients with a CK greater than 50 mL/min, except in patients undergoing hemodialysis (Table 2).

Table 2. Recommended doses of cefepime for adults.

* On the day of dialysis, the drug injection must be performed after the dialysis procedure is complete.

If only the serum creatinine concentration is known, then the CK can be determined using the formulas below.

Men: CK (ml/min) = body weight (kg)×(140 – age) : 72× plasma creatinine (mg/dL).

Women: CK (mL/min) = the rate in men×0.85.

Hemodialysis removes approximately 68% of the drug dose in 3 hours. In continuous ambulatory peritoneal dialysis, the drug can be used in the initial recommended doses of 500 mg, 1 g, or 2 g, depending on the severity of the infection at 48-hour intervals.

In children with impaired renal function, dosing changes proportional to those taken in adults are recommended according to the table below.

Children aged 1 month to 12 years (with body weight ≤ 40 kg):

pneumonia,

complicated urinary tract infections.

Calculation of CK values in children

CK (ml/min/1.73 m2) = 0.55 × height (cm): plasma creatinine (mg/dL) or

CK (ml/min/1.73 m2) = 0.52×growth (cm): plasma creatinine (mg/dL) -3.6.

Interaction

Pharmaceutically incompatible with other antimicrobial drugs and heparin.

Incompatible with metronidazole solution (before administering metronidazole solution to prevent infections during surgical interventions the infusion system should be flushed from cefepime solution).

Increases nephro- and ototoxicity of aminoglycosides.

Special Instructions

In case of pseudomembranous colitis with prolonged diarrhea, discontinue and prescribe vancomycin (oral) or metronidazole. Cross-over hypersensitivity is possible in patients with allergic reactions to penicillins. In combined severe renal and hepatic insufficiency the plasma concentration of the drug should be determined regularly (the dose should be adjusted depending on the CK).

In long-term treatment it is necessary to monitor regularly peripheral blood count, liver and renal function parameters. At mixed aerobic-anaerobic infection it is reasonable to combine it with medicines active against anaerobes before identification of pathogens. Patients with meningeal dissemination from a distant focus of infection, suspected meningitis or a confirmed diagnosis of meningitis should be prescribed an alternative antibiotic with proven clinical efficacy for this situation.

Possible positive Coombs test, false positive glucose test in urine. Prepared solution should be stored up to 24 hours at room temperature or within 7 days – in refrigerator. Color change does not affect the activity of the drug.

Contraindications

Hypersensitivity to Cefepim or L-arginine, as well as to cephalosporin antibiotics, penicillins or other β-lactam antibiotics. Pediatric age up to 2 months.

.

Side effects

Allergic reactions: skin rash (including erythematous rash), itching, fever, anaphylactoid reactions, positive Coombs reaction, eosinophilia, erythema multiforme (including Stevens-Johnson syndrome), rarely – toxic epidermal necrolysis (Lyell syndrome).

Local reactions: when administered intravenously – phlebitis, when administered intravenously – hyperemia and pain at the injection site.

Nervous system disorders: headache, dizziness, insomnia, paresthesia, anxiety, confusion, convulsions.

Urinary system disorders: vaginitis.

Urinary system disorders: impaired renal function.

Digestive system disorders: diarrhea, nausea, vomiting, constipation, abdominal pain, dyspepsia, pseudomembranous colitis.

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

Respiratory system: cough.

Particular system disorders: tachycardia, dyspnea, peripheral edema.

Laboratory measures: decrease of hematocrite, increase of prothrombin time, increase of urea concentration, hypercreatininemia, hypercalcemia, increase of liver transaminases and alkaline phases activity, hyperbilirubinemia.

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