Cefepime - instructions for use, dose, side effects, contraindications

Antibacterial agent from the group of cephalosporins of the IV generation. It acts bactericidal, disrupting the synthesis of the cell wall of microorganisms. Has a wide spectrum of action against Gram-positive and Gram-negative bacteria, strains resistant to aminoglycosides and / or cephalosporin antibiotics III generation. It is highly resistant to hydrolysis of most beta-lactamases and rapidly penetrates into gram-negative bacterial cells. Inside the bacterial cell, the molecular target is penicillin-binding proteins.

Active in vivo and in vitro in relation to 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 (but the clinical significance is unknown) in relation to gram-positive aerobes:

Staphylococcus epidermidis (only methicillin-sensitive strains), Staphylococcus saprophytics, Streptococcus agalactiae (group B);

Gram-negative aerobes: Acinetobacter calcoaceticus subsp. Iwoff, Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, Haemophilus influenzae (including strains producing beta-lactamase), Hafnia alvei, Klebsiella oxytoca, Moraxella catarrhalis (including strains producing beta-lactamases), Morganella morganii, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Serratia marcescens; most strains Enterococci, in t.ch. Enterococcus faecalis, methicillin-resistant staphylococci, Stenotrophomonas (formerly known as Xanthomonas maltophilia and Pseudomonas maltophilia), Clostridium difficile.

Pharmacokinetics:Bioavailability of 100%. Time to reach the maximum concentration in the blood plasma after intramuscular injection at a dose of 0.5 g - after 1-2 hours. The maximum concentration in the blood plasma (Cmax) with a / m introduction in doses of 0.5 g, 1 g and 2 g - 14 , 30 and 57 μg / ml, respectively; time to achieve an average therapeutic concentration in blood plasma - 12 h.

Mean concentrations (μg / ml) of cefepime in blood plasma the of adults after a single thirty-minute dose infusion of 500 mg, 1 g:

Table No. 1:

The dose of cefepime	0.5 h	1 h	2h	4h	8h	12 h
500 mg IM	8,2	12,5	12,0	6,9	1,9	0,7
1 g IM	14,8	25,9	26,3	16,0	4,5	1,4

High concentrations are determined in urine, bile, peritoneal fluid, blister exudate, bronchial mucus secretion, sputum, prostate tissue, appendix and gallbladder. The volume of distribution - 0.25 l / kg, in children from 2 months to 16 years - 0.33 l / kg. Connection with plasma proteins - 20%.

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. In patients with severe impairment of T1 / 2 kidney function with hemodialysis -13 hours, with continuous peritoneal dialysis - 19 hours. The dose of the drug in patients with impaired renal function should be selected individually. Patients over 65 years of age with normal renal function do not require a dose adjustment of cefepime

The pharmacokinetics of cefepime in patients with impaired liver function or cystic fibrosis is not changed. Dose adjustments for these patients are not required.

Indications:Complicated and uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli.

Contraindications:Hypersensitivity to the components that make up the drug (including antibiotics of cephalosporin class, penicillins and other beta-lactam antibiotics); children under 12 years (for this dosage form).

Carefully:Diseases of the gastrointestinal tract (including in the anamnesis): pseudomembranous enterocolitis, ulcerative colitis, regional enteritis or antibiotic-associated colitis; chronic renal failure.

Pregnancy and lactation:When pregnancy is used only if the intended benefit for the mother exceeds the risk to the fetus. During treatment with the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Doses of the drug vary depending on the sensitivity of the microorganisms of the pathogens, the severity of the infection, as well as the state of kidney function in the patient. Complicated or uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli: 0.5-1 g every 12 hours for 7-10 days.

In patients with impaired renal function (creatinine clearance <30 ml / min), the dose of the drug should be adjusted.The initial dose of Cefepime should be the same as for patients with normal renal function. The recommended maintenance doses of the drug are shown in the table.

Creatinine clearance (ml / min)	Recommended maintenance doses
>50	1 g every 12 h (Usual dose, no adjustment required)	500 mg every 12 hours (Usual dose, no adjustment required)
30-50	1 g every 12 h	500 mg every 12 hours
11-29	500 mg every 24 hours	500 mg every 24 hours
<10	250 mg every 24 hours	250 mg every 24 hours

Patients on hemodialysis on day 1 are given 1 g, then 0.5 g every 24 hours for all infections. On the day of hemodialysis, the drug is administered after the end of the hemodialysis session; it is desirable to enter cefepime every day at the same time. Data on the use of the drug in children older than 12 years with concomitant chronic renal failure are not available, however, given the similarity of pharmacokinetics in children and adults, the dosage regimen (dose reduction or increase in the interval between administrations) in children with chronic renal failure is similar to the dosing regimen in adults .

Introduction of the drug: Intramuscular injection

Cefepime is dissolved in sterile water for injection, 5% glucose solution for injection or 0.9% solution of sodium chloride for injection,bacteriostatic water for injection with paraben or benzyl alcohol, 0.5% or 1% solution of lidocaine hydrochloride, as indicated in Table 2.

table number 2:

Volume of dilution solution (ml)

The approximate volume of the solution obtained (ml)

Approximate concentration of cefipime (mg / ml)

Intramuscular administration:

500 mg / bottle

1,3

1,8

280

1 g / bottle

2,4

3,6

280

Side effects:

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

From the nervous system: headache, dizziness, insomnia, paresthesia, anxiety, confusion, convulsions.

From the genitourinary system: vaginitis.

From the urinary system: impaired renal function.

From the digestive system: diarrhea, nausea, vomiting, constipation, abdominal pain,

dyspepsia, pseudomembranous enterocolitis.

From the hematopoiesis: anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, hemolytic anemia, bleeding.

From the respiratory system: cough.

From the cardiovascular system: pain in the chest, tachycardia, dyspnea, peripheral edema.

Laboratory indicators: a decrease in hematocrit, an increase in prothrombin time, an increase in urea concentration, hypercreatininaemia, hypercalcemia, an increase in the activity of "hepatic" transaminases and alkaline phosphatase, and hyperbilirubinemia.

Local reactions: hyperemia and soreness at the injection site.

Other: pain in the throat, increased sweating, back pain, asthenia, development of superinfection, oropharyngeal candidiasis.

Overdose:Symptoms (often occur in patients with chronic renal failure): convulsions, encephalopathy, agitation. Treatment: hemodialysis.

Interaction:

Pharmaceutically incompatible with other antimicrobial drugs and heparin.

Diuretics, polymyxin B reduce the tubular secretion of cefepime and increase its concentration in serum, prolong the half-life, increase nephro-toxicity (the risk of developing nephronecrosis).

Nonsteroidal anti-inflammatory drugs, slowing the excretion of cephalosporins, increase the risk of bleeding.

With the simultaneous administration of bactericidal antibiotics (aminoglycosides), synergism appears with bacteriostatic (macrolides, chloramphenicol, tetracyclines) - antagonism.

Incompatible with a solution of metronidazole. Increases the nephro- and ototoxicity of aminoglycosides.

Special instructions:

When using cefepime, pseudomembranous colitis may occur. Therefore, it is important to bear this diagnosis in case of diarrhea during treatment with the drug. Light forms of colitis do not require special treatment, it is enough to stop the introduction of the drug; mild or severe cases may require special treatment.

There is a possibility of cross-over hypersensitivity in patients with allergic reactions to penicillins.

When combined severe renal and hepatic insufficiency should regularly determine the concentration of the drug in the plasma (dose adjustment is performed depending on the creatinine clearance).

With prolonged treatment, regular monitoring of peripheral blood, indicators of the functional state of the liver and kidneys is necessary.

With a mixed aerobic-anaerobic infection before identifying pathogens, a combination with drugs active against anaerobes is appropriate.Patients who have a meningeal dissemination from a distant foci of infection, suspicions of meningitis or a diagnosis of meningitis are confirmed, an alternative antibiotic with confirmed clinical efficacy should be prescribed.

It is possible to detect a positive Coombs test, a false positive test for glucose in the urine.

Form release / dosage:Powder for the preparation of solution for intramuscular injection of 0.5 g and 1.0 g.

Packaging:0.5 g or 1.0 g of active substance into 10 ml vials. The bottle together with the instruction for use is placed in a bundle. 10 bottles together with instructions for use are placed in a box of cardboard. For hospital: 50 vials and 5 instructions for use are placed in a box of cardboard

Storage conditions:List B. In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005870/09

Date of registration:20.07.2009

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Cefepim (Cefepime)