CEFEPIME POWDER FOR SOLUTION IN/IN AND IN/M 1G

Mechanism of action

Cephalosporin antibiotic IV generation for parenteral use. It has a bactericidal effect, disrupting the synthesis of the cell wall of microorganisms.

It is active against most gram-negative bacteria, incl. producing β-lactamase, including Pseudomonas aeruginosa. More active than III generation cephalosporins, with respect to gram-positive cocci.

Not active against Enterococcus spp., Listeria spp., Legionella spp., Some anaerobic bacteria (Bacteroides fragilis, Clostridium difficile).

Cefepime is characterized by high stability against various plasmid and chromosomal β-lactamases.

Pharmacokinetics

Plasma protein binding is less than 19% and does not depend on the concentration of cefepime in serum.

Therapeutic concentrations of cefepime are found in urine, bile, peritoneal fluid, blister exudate, bronchial mucous membrane, sputum, prostate tissue, appendix and gall bladder, cerebrospinal fluid with meningitis.

In healthy people with on / in the introduction of cefepime at a dose of 2 g with an interval of 8 hours for 9 days was not observed cumulation in the body.

Average t1/2 From an organism on average makes about 2 h, the average general clearance - 120 ml / min. Cefepime is excreted by the kidneys, mainly by glomerular filtration (the mean renal clearance is 110 ml / min). In the urine about 85% of cefepime administered is detected unchanged.

In patients aged 65 years or older with normal renal function, the value of renal clearance is less than in younger patients.

In patients with impaired renal function increases T1/2. In patients with severe renal impairment who require hemodialysis, T1/2 averaging 13 hours, peritoneal dialysis - 19 hours

The pharmacokinetics of cefepime in patients with impaired liver function, cystic fibrosis is not changed.

The age and sex of the patients did not significantly affect the overall clearance of the body and Vd taking into account the amendment to the weight of each. With the introduction of cefepime at a dose of 50 mg / kg every 12 hours there was no cumulation, and with the introduction of the dose at the same dose every 8 hours in an equilibrium state Cmax, AUC and T1/2 increased by about 15%.

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms susceptible to cefepime: lower respiratory tract infections (including pneumonia and bronchitis), urinary tract infections (both complicated and uncomplicated), skin and soft tissue infections, intra-abdominal infections (including peritonitis and infections of the bile ways), gynecological infections, septicemia, neutropenic fever (as an empirical therapy), bacterial meningitis in children.

Prevention of infections during abdominal surgery.

Dosage and administration

Individual, depending on the sensitivity of the pathogen, the severity of the infection, as well as the state of kidney function.

In / in the route of administration is preferable for patients with severe or life-threatening infections, especially with the threat of shock.

With the / m or / in the introduction of adults and children weighing more than 40 kg with normal kidney function, a single dose is 0.5-1 g, the interval between injections is 12 hours. In severe infections, a dose of 2 g is administered iv, every 12 h

In order to prevent infections during abdominal surgery, used in combination with Metronidazole according to the scheme.

For children from 2 months of age, the maximum dose should not exceed the recommended dose for adults. The average dose for children weighing up to 40 kg in complicated or uncomplicated urinary tract infections (including pyelonephritis), uncomplicated infections of the skin and soft tissues, 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. For severe infections, longer treatment may be required.

In case of impaired renal function (CC less than 30 ml / min), correction of the dosing regimen is necessary. The initial dose of cefepime should be the same as for patients with normal renal function. Maintenance doses are determined based on CC values ​​or serum creatinine concentration.

With hemodialysis, after about 3 hours, approximately 68% of the total amount of cefepime is removed from the body.At the end of each session, you must enter a repeated dose equal to the initial dose. In patients on continuous ambulatory peritoneal dialysis, cefepime can be used in the average recommended dose, i.e. 500 mg, 1 g or 2 g, depending on the severity of the infection, with an interval between injections of a single dose of 48 hours.

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

Side effect

Gastrointestinal: diarrhea, nausea, vomiting, colitis (including pseudomembranous colitis) are possible; rarely - abdominal pain, constipation, change in taste.

Allergic reactions: possible - rash, itching, hives; rarely - Anaphylactic reactions.

Nervous system: headaches are possible; rarely - dizziness, paresthesia; in some cases - seizures.

Dermatologic: rarely - redness of the skin. Most common in children is rash.

Hemic and lymphatic: possible anemia.

From the laboratory research indicators: possible increase in the activity of ALT, AST, ALP, increase in total bilirubin, eosinophilia, an increase in prothrombin time; rarely, a temporary increase in blood urea nitrogen and / or serum creatinine, transient thrombocytopenia, transient leukopenia and neutropenia; often - a positive Coombs test without hemolysis.

Other: fever, vaginitis, erythema are possible; rarely - genital pruritus, nonspecific candidiasis.

Local reactions: with IV infusion, phlebitis is possible, rarely inflammation); with intramuscular administration, inflammation or pain is possible.

Contraindications

Hypersensitivity to cefepime or L-arginine, as well as to cephalosporin antibiotics, penicillins or other beta-lactam antibiotics.

Use during pregnancy and lactation

Adequate and strictly controlled studies of the safety of cefepime in pregnancy have not been conducted; application is possible only under medical supervision.

Cefepime is excreted in breast milk at very low concentrations. During lactation use with caution.

ATexperimental studies no effect on reproductive function and fetotoxic effect of cefepime was revealed.

Application for violations of kidney function

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

Use in children

The safety and efficacy of cefepime in children under the age of 2 months has not been established. For children older than 2 months, use is possible according to the dosing regimen. Children with impaired renal function are recommended the same changes in dosing regimen as adults, because the pharmacokinetics of cefepime in adults and children has a similar character.

Special notes

When used in patients who are at increased risk of infection due to mixed aerobic / anaerobic microflora (including in cases where one of the pathogens is Bacteroides fragilis), it is recommended to administer a drug that is active against cefepime in order to identify the pathogen. anaerobes.

It is used with caution in patients at risk of developing allergic reactions, especially to drugs.

With the development of allergic reactions, cefepime should be abolished.

For serious immediate-type hypersensitivity reactions, epinephrine (adrenaline) and other forms of supportive treatment may be required.

If diarrhea occurs during treatment, consideration should be given to the possibility of developing pseudomembranous colitis. In such cases, cefepime should be discontinued immediately and, if necessary, appropriate treatment should be given.

With the development of superinfection, cefepime should be immediately discontinued and appropriate treatment should be prescribed.

When using other cephalosporin antibiotics have been observed rash, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, colitis, renal failure, toxic nephropathy, aplastic anemia, hemolytic anemia, bleeding, seizures, abnormal liver function, including cholestasis , false positive test results on urine glucose.

The safety and efficacy of cefepime in children under the age of 2 months has not been established.

With extreme caution, cefepime is used together with aminoglycosides and "loop" diuretics.

Drug interaction

With the simultaneous introduction of a solution of cefepime with solutions of metronidazole, Vancomycin , Gentamicin , tobramycin sulfate and netilmicin sulfate, pharmaceutical interaction is possible.