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 wide spectrum of action against Gram-positive and Gram-negative bacteria, strains resistant to aminoglycosides and/or 3rd generation cephalosporin antibiotics. Highly resistant to hydrolysis of most beta-lactamases and quickly penetrates into 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 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), Clostridium difficile are not sensitive to cefepime.

Pharmacokinetics

Bioavailability 100%. Time of reaching maximum concentration (TCmax) after intravenous and intramuscular administration at a dose of 0.5 g is by the end of infusion and 1-2 hours, respectively.

The maximum concentration (Cmax) when administered intramuscularly in doses of 0.5, 1 and 2 g – 14, 30 and 57 mcg/ml, respectively; when administered intravenously in doses of 0.25, 0.5, 1 and 2 g – 18, 39, 82 and 164 mcg/ml, respectively; time to reach mean therapeutic plasma concentration is 12 hours; mean therapeutic concentration when administered intramuscularly is 0.2 mcg/ml, when administered intravenously is 0.7 mcg/ml.

High concentrations are detected in urine, bile, peritoneal fluid, blister exudate, bronchial mucous secretion, sputum, prostate, 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 with plasma proteins is 20%. Metabolized in the liver and kidneys by 15%.

Half-life (T1/2) is 2 hours, total clearance – 120 ml/minute, renal clearance – 110 ml/minute. It is excreted by the kidneys (by glomerular filtration in unchanged form – 85%), with breast milk. T1/2 in hemodialysis is 13 hours, in continuous peritoneal dialysis – 19 hours.

Indications

Active ingredient

Composition

1 vial contains:

the active ingredient:

cefepime hydrochloride 1 g.

How to take, the dosage

The dosing regimen of Cefepime is individualized depending on the sensitivity of the pathogen, the severity of infection, and the state of renal function.

Intravenous route of administration is preferable for patients with severe or life-threatening infections, especially with the threat of shock.
When intramuscular or intravenous administration in adults and children with body weight over 40 kg with normal renal function the single dose is 0.5-1 g, the interval between injections is 12 hours. For severe infections it is administered intravenously in dose of 2 g every 12 hours.
For prophylaxis of infections during cavity surgical operations it is used in combination with metronidazole according to the scheme.

In children aged from 2 months the maximum dose should not exceed the recommended dose for adults. The average dose for children with body weight up to 40 kg in complicated or uncomplicated urinary tract infections (including pyelonephritis), uncomplicated skin and soft tissue infections, pneumonia, 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. In severe infections more prolonged treatment may be required.

In case of impaired renal function (CKR less than 30 ml/min) dosage regimen should be corrected. The initial dose of cefepime should be the same as in patients with normal renal function. Maintenance doses are determined depending on CK values or serum creatinine concentrations

In hemodialysis approximately 68% of the total amount of cefepime is removed from the body in 3 hours. At the end of each session, a repeat dose equal to the initial dose should be administered. In patients on continuous ambulatory peritoneal dialysis, cefepime 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 of 48 hours between single doses.

Children with impaired renal function are recommended the same dosing regimen as adults because the pharmacokinetics of cefepime in adults and children are similar.

Interaction

Pharmaceutically incompatible with other antimicrobial agents and heparin.
Diuretics, aminoglycosides, polymyxin B reduce tubular secretion of cefepime and increase its serum concentrations, prolong T1/2, increase nephrotoxicity (increased risk of nephronecrosis). Cefepime increases ototoxicity of aminoglycosides.

Non-steroidal anti-inflammatory drugs, by slowing excretion of cephalosporins, increase the risk of bleeding. When concomitant administration with bactericidal antibiotics (aminoglycosides) synergism is manifested with bacteriostatic ones (macrolides, chloramphenicol, tetracyclines) – antagonism.

Incompatible with metronidazole solution (before administering metronidazole solution for prevention of infections during surgical interventions the infusion system should be flushed from cefepime solution). To avoid possible drug interaction with other drugs, cefepime solutions (as well as most other beta-lactam antibiotics) should not be administered simultaneously with vancomycin, gentamicin, tobramycin, netilmicin solutions. When administering cefepime with the above drugs, each antibiotic should be administered separately.

Special Instructions

Pseudomembranous colitis may occur with cefepime. It is therefore important to keep this diagnosis in mind if diarrhea occurs during treatment with the drug. Mild forms of colitis do not require special treatment, stopping the drug is sufficient; moderate or severe cases may require special treatment.

Possible cross-sensitivity 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 creatinine clearance).

With long-term treatment it is necessary to perform regular control of peripheral blood, liver and kidney function parameters.
In 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 the situation.

There may be a positive Coombs test, a false positive urine glucose test.

Contraindications

Side effects

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

Nervous system disorders: headache, dizziness, insomnia, paresthesias, anxiety, confusion, convulsions, encephalopathy (in the absence of dose correction in patients with renal dysfunction).

Urogenital system disorders: vaginitis.

Urinary system disorders: impaired renal function.

Gastrointestinal tract disorders: diarrhea, nausea, vomiting, constipation or diarrhea, abdominal pain, dyspepsia, pseudomembranous colitis.

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

Respiratory system: cough, chest pain.

Cardiovascular system: 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 phosphatase activity, hyperbilirubinemia, positive Coombs test (without hemolysis).

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

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

Overdose

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