Cefepime, vial, 1g

Composition

1 bottle contains:

Active ingredient:

Cefepimee hydrochloride 1 g

Pharmacological action

Cefepimee is an antibacterial agent from the group of cephalosporins of the IV generation. 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, strains resistant to aminoglycosides and / or cephalosporin antibiotics of the third generation. It is highly resistant to hydrolysis of most beta-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 (only methicillin-sensitive strains), 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 (only methicillin-sensitive strains), 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 maltophilia (formerly known as Xanthomonas maltophilia), and Clostridium difficile are not sensitive to Cefepimee.

Pharmacokinetics

Bioavailability is 100%. The time to reach the maximum concentration (TCmax) after intravenous and intramuscular use at a dose of 0.5 g is at the end of the infusion and 1-2 hours, respectively. The maximum concentration (Cmax) for intramuscular use in doses of 0.5,1 and 2 g is 14,30 and 57 mcg/ml, respectively; for intravenous use in doses of 0.25,0.5,1 and 2 g-18,39,82 and 164 mcg/ml, respectively; the time to reach the average therapeutic concentration in plasma is 12 hours; the average therapeutic concentration for intramuscular use is 0.2 mcg / ml, for intravenous use-0.7 mcg/ml.

High concentrations are detected in the urine, bile, peritoneal fluid, exudate of the blister, mucosal secretions of the bronchi, sputum, prostate gland, appendix and gallbladder. The volume of distribution is 0.25 l / kg, in children from 2 months to 16 years – 0.33 l/kg. Binding to plasma proteins is 20%. It is metabolized in the liver and kidneys by 15%.

Half-life (T1 / 2) – 2 hours, total clearance – 120 ml/min, renal clearance – 110 ml/min. It is excreted by the kidneys (by glomerular filtration in unchanged form-85%), with breast milk. T1 / 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, Enterobacter spp., and Bacteroides fragilis.
• Prevention of infections during oral surgery.

Use during pregnancy and lactation

During pregnancy, it is used only if the intended benefit to the mother exceeds the potential risk to the fetus. During treatment with the drug during lactation, breastfeeding should be discontinued.

Contraindications

• Hypersensitivity to the components included in the composition of the drug Cefepimee (including to antibiotics cephalosporins, penicillins and other beta-lactam antibiotics);
• children’s age up to 2 months (intravenous route of use) (safety and efficacy in children under the age of 2 months have not been established);
• children up to age 12 years (for intramuscular route of use).

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.

Gastrointestinal disorders: 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, hypercalcemia, 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. Others: sore throat, thoracalgia, increased sweating, back pain, asthenia, development of superinfection, oropharyngeal candidiasis.

Interaction

Pharmacologically incompatible with other antimicrobial drugs and heparin. Diuretics, aminoglycosides, and polymyxin B reduce the tubular secretion of Cefepimee and increase its concentration in the blood serum, prolong T 1/2, and increase nephrotoxicity (the risk of developing nephronecrosis increases). 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), synergism is shown, with bacteriostatic antibiotics (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

The dosage regimen of Cefepimee is individual, depending on the sensitivity of the pathogen, the severity of the infection, and the state of kidney function.

The intravenous route of use is preferred for patients with severe or life-threatening infections, especially when shock is threatened.

When administered intramuscularly or intravenously to adults and children with a body weight of more than 40 kg with normal renal function, a single dose is 0.5-1 g, the interval between injections is 12 hours. For severe infections, it is administered intravenously at a dose of 2 g every 12 hours.

In order to prevent infections during oral surgery, it is used in combination with metronidazole according to the scheme.

For children over 2 months of age, the maximum dose should not exceed the recommended adult dose. The average dose for children weighing up to 40 kg with complicated or uncomplicated urinary tract infections (including pyelonephritis), uncomplicated skin and soft tissue infections, pneumonia, and empirical treatment of neutropenic fever is 50 mg / kg every 12 hours.

Patients with neutropenic fever and bacterial meningitis – 50 mg / kg every 8 hours.

The average duration of therapy is 7-10 days. Severe infections may require longer treatment.

In case of impaired renal function (creatinine clearance less than 30 ml / min), dosage adjustment is necessary. The initial dose of Cefepimee should be the same as for patients with normal renal function. Maintenance doses are determined depending on the values of creatinine clearance or serum creatinine concentration

During hemodialysis, approximately 68% of the total amount of Cefepimee is removed from the body in 3 hours. At the end of each session, a repeated dose equal to the initial dose should be administered. In patients undergoing continuous outpatient peritoneal dialysis, Cefepimee can be used in the average recommended doses, i. e. 500 mg,1 g or 2 g, depending on the severity of the infection, with an interval between single dose injections of 48 hours.

In children with impaired renal function, the same dosage changes are recommended as in adults, since the pharmacokinetics of Cefepimee in adults and children are similar.

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.

Product form

powder for solution preparation for intravenous and intramuscular use

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Cefepimee

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion

Purpose

For adults as prescribed by a doctor, Children as prescribed by a doctor, Pregnant women as prescribed by a doctor

Indications

Respiratory Tract Infections, Skin Infections, Biliary Tract Infections, Urinary Tract Infections, Bronchitis, Cholecystitis