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 vitro for the following microorganisms:

- Gram-positive aerobes, such as Staphylococcus aureus and Staphylococcus epidermidis (including strains producing beta-lactamase), Staphylococcus hominis, Staphylococcus saprophytics, other strains Staphylococcus spp., Streptococcus pyogenes (Group A), Streptococcus agalactiae (group B), Streptococcus pneumoniae, other beta-hemolytic Streptococcus spp. (groups FROM, G and F), Streptococcus bovis (groups D), Streptococcus viridans;

- Gram-negative aerobes, such as Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas putida and Pseudomonas stutzeri), Escherichia coli, Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella oxaenae), Enterobacter spp. (including Enterobacter cloacae, Enterobacter aerogenes, Enterobacter agglomerans and Enterobacter sakazakii), Proteus spp. (at Tom number of Proteus mirabilis and Proteus vulgaris), Acinetobacter calcoaceticus, Aeromonas hydrophila, Capnocytophaga spp., Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii), Campylobacter jejuni, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including strains, producing beta-lactamase), Haemophilus parainfluenzae, Hafnia alvei, Legionella spp., Morganella morganii, Moraxella catarrhalis (including strains, producing beta-lactamase), Neisseria gonorrhoeae (including strains, producing beta-lactamase), Neisseria meningitides, Providencia spp. (at Tom number of Providencia rettgeri, Providencia stuartii), Salmonella spp., Serratia spp. (at Tom number of Serratia marcescens, Serratia liquefaciens), Shigella spp., Yersinia enterocolitica;

- anaerobes, such as Prevotella spp. (at Tom number of Prevotella melaninogenicus), Clostridium perfringens, Fusobacterium spp., Mobiluncus spp., Peptostreptococcus spp., Veillonella spp., Bacteroides spp. (including Bacteroides melaninogenicus and others related to Bacteroides microorganisms of the oral cavity).

Resistance. To cefepime are stable Bacteroides fragilis, Clostridium difficile, Staphylococci resistant to methicillin, pneumococci, resistant to penicillin, some strains Xanthomonas maltophilia, most strains of enterococci, including Enterococcus faecalis.

Pharmacokinetics:

Bioavailability cefepime - 100%. AT table 1 average plasma concentrations in adults at different times after a single 30-minute infusion of 1.0 g of cefepime, the maximum concentration (C_m_Oh) and the area under the curve "concentration-time" (AUC).

Table 1

Options	After intravenous administration, 1.0 g
The average concentration in the blood plasma (time in hours after administration)	78.7 μg / ml (0.5 h)
	44.5 μg / ml (1 hour)
	24.3 μg / ml (2 hours)
	10.5 μg / ml (4 hours)
	2.4 μg / ml (8 hours)
	0.6 μg / ml (12 h)
FROM_m_Oh	81.7 μg / ml
AUC	148.5 μg / ml / hr

Cefepime is absorbed completely after intramuscular injection. AT table 2 average concentrations in the blood plasma at different times after a single intramuscular injection of 1.0 g, C_max, time to reach the maximum concentration (TC_m_Oh) and AUC.

table 2

Options	After intramuscular injection, 1.0 g
The average concentration in the blood plasma (time in hours after administration)	14.8 μg / ml (0.5 h)
	25.9 μg / ml (1 hour)
	26.3 μg / ml (2 hours)
	16.0 μg / ml (4 hours)
	4.5 μg / ml (8 hours)
	1.4 μg / ml (12 hours)
FROM_m_Oh	29.5 μg / ml
TS_m_Oh	1.6 hrs
AUC	137.0 μg / ml / hr

The average volume of distribution is 0.25 l / kg; in children from 2 months. up to 16 years - 0.33 l / kg.

About 20% of the administered dose is associated with plasma proteins.

High concentrations are determined in urine, bile, peritoneal fluid, blister exudate, bronchial mucosa, sputum, prostate gland, appendix and gallbladder.

The half-life is 2 hours; at a hemodialysis-13 ch, at a continuous peritoneal dialysis-19 ch.

Approximately 15% of the dose is metabolized in the liver and kidneys, and approximately 85% is excreted unchanged in the urine.

Indications:

- pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including cases of association 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 (only methicillin-sensitive strains,), Streptococcus pyogenes.

- complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroidesfragilis.

Contraindications:Hypersensitivity to cefepime and other beta-lactam antibiotics, including cephalosporins, penicillins, carbapenems,monobactams; hypersensitivity to arginine; I trimester of pregnancy; children age up to 2 months.

Carefully:

Patients with impaired renal function; with nonspecific ulcerative colitis, including in the anamnesis; Children under 12 years due to the lack of research.

Pregnancy and lactation:

Use in the II and III trimesters of pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

Cefepime is excreted in breast milk, so breastfeeding should be discontinued when taking the drug.

Dosing and Administration:

Enter intravenously (jet, drip) or intramuscularly (only with complicated or uncomplicated urinary tract infections of mild and moderate severity caused by Escherichia coli).

The dose and route of administration depend on the location, type and type of infection, kidney function and age of the patient.

Adults. AT table 3 recommended dosages, routes of administration and duration of therapy depending on the nature and localization of the infection.

Table 3

The nature and location of infection	Single dose, route and frequency of administration	Duration of therapy (days)
Severe and severe pneumonia	1.0 - 2.0 g intravenously every 12 h	10
Moderate uncomplicated and complicated infections of the kidneys and urinary tract, including pyelonephritis	0.5 - 1.0 g intravenously or intramuscularly every 12 hours	7-10
Severe uncomplicated and complicated infections of the kidneys and urinary tract, including pyelonephritis	2.0 g intravenously every 12 h	10
Complicated intra-abdominal infections (in combination with metronidazole)	2.0 g intravenously every 12 h	7-10
Severe and severe uncomplicated skin and soft tissue infections	2.0 g intravenously every 12 h	10
Neutropenic fever; life-threatening infection	2.0 g intravenously every 8 hours	7

Patients with impaired hepatic function. Patients in this category do not need to reduce the dose of cefepime.

Patients with impaired renal function. AT table 4 recommended recommended dosing regimens for patients with normal renal function, with renal failure and for patients on peritoneal dialysis or hemodialysis.

Table 4

Ground clearanceeatinin (ml / min)	Single dose and frequency of administration
1	2	3		4	5
> 60 (normal renal function)	0.5 g every 12 h	1.0 g every 12 h		2.0 g every 12 h	2.0 g every 8 hours
1	2		3	4	5
30-60	0.5 g every 24 hours		1.0 g every 24 h	2.0 g every 24 h	2.0 g every 12 h
11-29	0.5 g every 24 hours		0.5 g every 24 hours	1.0 g every 24 h	2.0 g every 24 h
<11	0,25g every 24h		0.25 g every 24h	0.5 g every 24 hours	1.0 g every 24 h
Peritoneal dialysis	0.5 g every 48 h		1.0 g every 48 h	2.0 g every 48 h	2.0 g every 48 h
Hemodialysis	1.0 g on the first day of hemodialysis, then 0.5 g every 24 hours				1.0 g every 24 h

Patients on hemodialysis, cefepime should be administered after the end of hemodialysis, preferably at the same time.

Children from 2 months to 16 years. In children from 2 months. up to 16 years and with a body weight of up to 40 kg, the recommended dosing regimen for all indications (excluding febrile neutropenia) is 50 mg / kg every 12 hours intravenously; with febrile neutropenia - 50 mg / kg every 8 hours. Duration of treatment as in adults.

Intravenous administration.

Inkjet: the preparation with a dosage of 1.0 g is dissolved in 10 ml of sterile water for injection or 5% solution of dextrose (glucose), or 0.9% sodium chloride solution (Table 5); injected within 3-5 minutes.

Drip (for at least 30 minutes: for intravenous drip, the drug is dissolved in a small volume (5-10 ml) of one of the following solutions: 0.9% sodium chloride solution, 5% or 10% dextrose (glucose) solution, sodium lactate solution,mixture of 5% dextrose solution and 0.9% sodium chloride solution, Ringer's lactate mixture and 5% dextrose solution, and volume is adjusted to 50 ml or 100 ml with the same solution (table 5); injected for at least 30 minutes. During the infusion it is recommended to suspend the introduction of other solutions.

Intramuscular injection. The drug with a dosage of 1.0 g is dissolved in 2.4 ml of sterile water for injection or 0.9% solution of sodium chloride, or 0.5-1% solution of lidocaine hydrochloride (table 5); injected deep into the muscle, for example, in the upper outer quadrant of the buttocks.

With intramuscular injection, preliminary aspiration is necessary to prevent the needle from entering the vessel and to prevent the solution, especially lidocaine, from entering the blood!

Preparation of the solution. AT table 5 The volumes of the solvent are presented depending on the required dosage and route of administration, as well as the approximate concentrations of the preparation obtained.

Table 5

Dosage and route	Volume of solvent	Exemplary	Approximate
introduction of	(ml)	recoverable volume	concentration
		(ml)	preparation (mg / ml)
Intravenous administration (jet)
1.0 g	10,0	11,3	100
Intravenous injection (drip)
1.0 g	50,0	50,0	20
1.0 g	100,0	100,0	10
Intramuscular injection
1.0 g	2,4	3,6	280

The resulting solution should not contain any particles!

The prepared solutions of the preparation for intravenous and intramuscular injections are stored for no more than 24 hours at room temperature or for not more than 7 days in a refrigerator at a temperature of 2-8 ° C. Darkening of the solution does not indicate a change in the activity of the drug.

Side effects:

Allergic reactions: skin rash (including erythema), itching, fever, anaphylactoid reactions, 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: extremely rare - a violation of kidney function, toxic nephropathy.

From the gastrointestinal tract: diarrhea, nausea, vomiting, constipation, abdominal pain, indigestion; with prolonged therapy - dysbiosis; extremely rarely - pseudomembranous enterocolitis.

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

From the respiratory system: cough, shortness of breath, sore throat.

From the CAS side: tachycardia, chest pain.

Local reactions: at intravenous introduction - phlebitis, at intramuscular introduction - a hyperemia and morbidity in a place of introduction.

Laboratory indicators: decrease in hematocrit, increased prothrombin time, increased urea concentration, hypercreatininemia, hypercalcemia, increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia, positive direct Coombs test, false positive urine glucose test.

Other: pain in the throat, increased sweating, back pain, asthenia, peripheral edema, candidiasis.

Overdose:

It often occurs in patients with chronic renal failure.

Symptoms: convulsions, encephalopathy, neuromuscular excitation.

Treatment: with renal failure - hemodialysis; careful observation and maintenance therapy with normal functioning of the kidneys.

Interaction:

The solution of cefepime should not be mixed with solutions of metronidazole, vancomycin, gentamicin, tobramycin, netilmicin, aminophylline. If necessary, these solutions are administered separately.

The drug solution can be added to the solution of ampicillin if the concentration of each of the mixing solutions does not exceed 40 mg / ml.

Diuretics, aminoglycosides and polymyxin B reduce the tubular secretion of cefepime, prolong the half-life, increase the concentration of the drug in the blood; increase nephrotoxicity.

Non-steroidal anti-inflammatory drugs slow the excretion of cephalosporins and increase the risk of bleeding.

When used concomitantly with aminoglycosides, it exhibits synergism, with macrolides, chloramphenicol or tetracyclines - antagonism.

Special instructions:If there is a suspicion of an aerobic anaerobic infection, before identifying the pathogen, an additional prescription of an antibacterial agent active against anaerobic microorganisms is recommended; preparations should be entered separately!

Patients who are likely to be disseminated from the focus of the infection and suspected of having meningitis should be prescribed an alternative antibiotic with clinically proven effectiveness in meningitis.

In the case of pseudomembranous colitis, the drug is canceled; moderate and severe complications require the appointment of vancomycin or metronidazole.

There is a possibility of cross-over hypersensitivity in patients with allergic reactions to penicillins. In case of an allergic reaction, use of the drug is stopped; a serious immediate reaction may require epinephrine, a glucocorticoid and other urgent measures.

In severe renal / hepatic insufficiency, the concentration of the drug in the blood should be monitored regularly.

With a treatment duration of more than 10 days, regular monitoring of blood and functional status of the liver and kidneys is necessary.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection, 1.0 g.

Packaging:

By 1,0 g in vials polymer or glass.

For 1 bottle with instructions for use in a pack of cardboard.

For 5 or 30 bottles with instructions for use in a cardboard box.

Storage conditions:List B. In the dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:2 years.Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-010516/09

Date of registration:24.12.2009

The owner of the registration certificate:Pharmaceutical firm LEKKO, ZAO Pharmaceutical firm LEKKO, ZAO Russia

Manufacturer: & nbsp

Pharmaceutical firm LEKKO, ZAO Russia

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Cefepim (Cefepime)