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

Cefepime is a fourth generation cephalosporin antibiotic for parenteral administration; acts intracellularly bactericidal by blocking the peptidoglycan polymerase, disrupting the biosynthesis of the cell wall of the microorganism; highly resistant to most beta-lactamases. Inside the bacterial cell, the molecular target is the penicillin binding protein.

Cefepime has a wide spectrum of action against gram-positive and gram-negative bacteria, as well as strains,resistant to aminoglycosides and / or cephalosporin antibiotics of the third generation; exhibits significantly greater antibacterial activity relative to the beta-lactamase producer microorganisms of the extended spectrum as compared to the third generation cephalosporins; in vitro is active against 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 (groups 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 jreundii), 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 meningitidis, 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., Veillomlla spp., Bacteroides spp. (including Bacteroides melaninogenicus and other Bacteroides microorganisms of the oral cavity).

Resistance

TO cefepime are stable Bacteroides fragilis, Clostridium difficile, staphylococci, punchtent to methicillin, pneumococci, resistant to penicillin, some strains Xanthomonas maltophilia, most strains 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 500 mg and 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 of 500 mg	After intravenous administration, 1.0 g
The average concentration in the blood plasma (time in hours after administration)	38.2 μg / ml (0.5 h)	78.7 μg / ml (0.5 h)
	21.6 μg / ml (1 hour)	44.5 μg / ml (1 hour)
	11.6 μg / ml (2 hours)	24.3 μg / ml (2 hours)
	5.0 μg / ml (4 hours)	10.5 μg / ml (4 hours)
	1.4 μg / ml (8 hours)	2.4 μg / ml (8 hours)
	0.2 μg / ml (12 hours)	0.6 μg / ml (12 hours)
FROM_m_Oh	39.1 μg / ml	81.7 μg / ml
AUC	70.8 μg / ml / hr	148.5 μg / ml / hr

Cefepime is absorbed completely after intramuscular injection. AT table 2 The average concentrations in the blood plasma at different times after a single intramuscular injection of 500 mg and 1.0 g, C_m_Oh, time to reach the maximum concentration (TC_m_Oh) and AUC.

table 2

Options	After intramuscular injection, 500 mg	After intramuscular injection, 1.0 g
The average concentration in the blood plasma (time in hours after administration)	8.2 μg / ml (0.5 h)	14.8 μg / ml (0.5 h)
	12.5 μg / ml (1 hour)	25.9 μg / ml (1 hour)
	12.0 μg / ml (2 hours)	26.3 μg / ml (2 hours)
	6.9 μg / ml (4 hours)	16.0 μg / ml (4 hours)
	1.9 μg / ml (8 hours)	4.5 μg / ml (8 hours)
	0.7 μg / ml (12 hours)	1.4 μg / ml (12 hours)
FROM_m_Oh	13.9 μg / ml	29.5 μg / ml
TFROM_m_Oh	1.4 h	1,6h
AUC	60.0 μg / ml / hr	137.0 μg / ml / hr

The average volume of distribution is 0.25 l / kg; in children from 2 months 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; with hemodialysis - 13 hours, with continuous peritoneal dialysis-19h.

Approximately 1.5% 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 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 with intra-abdombinfections (in combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp, Bacteroides fragilis.

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.

The nature and location of infections	Single dose, route and frequency of administration	Duration of therapy (days)
Severe and severe pneumonia	1.0-2.0 g intravenously. every 12 hours	10
Mediocrisy 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
Heavy 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 infections of the skin and soft tissue	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

Creatinine clearance (ml / min)	Single dose and frequency of administration
> 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
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	0.25 g every 24 h	0.25 g every 24 h	0.5 g every 24 hours	1.0 g every 24 h
Peritoneal dialysis	0.5 every 48 hours	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 hours 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 to 16 years and with a body weight of up to 40 kg, the recommended dosing regimen is: for all indications (excluding febrile neutropenia) - 50 mg / kg every 12 hours intravenously; at. febrile neutropenia - 50 mg / kg every 8 hours. Duration of treatment, as in adults.

Intravenous administration

Streaming

The drug 500 mg is dissolved in 5 ml and a dose of 1.0 g in 10 ml of sterile water for injection or 5% solution of dextrose (glucose), or 0.9% solution of sodium chloride (table 5); injected within 3-5 minutes.

Chapel (for at least 30 minutes)

For intravenous drip administration, the preparation 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, 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 500 mg is dissolved in 1.3 ml and a dose of 1.0 g in 2.4 ml of sterile water for injection or 0.9% solution of sodium chloride, or 0.5-1.0% solution of lidocaine hydrochloride (table 5); injected deep into the muscle mass, for example, in the upper outer quadrant of the buttocks.

With intramuscular injection, aspiration should be performed to prevent the needle from entering the vessel and to prevent the injection of a solution, especially lidocaine, into 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 of administration	Volume of solvent (ml)	Estimated recoverable volume (ml)	Approximate concentration of the preparation (mg / ml)
Intravenous administration (jet)
500 mg	5,0	5,6	100
1.0 g	10,0	11,3	100
Intravenous injection (drip)
500 mg	50,0	50,0	10
500 mg	100,0	100,0	5
1.0 g	50,0	50,0	20
1.0 g	100,0	100,0	10
Intramuscular injection
500 mg	1,3	1,8	280
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, itching, fever, urticaria; extremely rare - anaphylactoid reactions, Stevens-Johnson syndrome (malignant variant of exudative erythema), Lyell's syndrome (acute epidermal necrolysis).

From the nervous system: headache, dizziness, insomnia, paresthesia, anxiety, extremely rarely 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, constipation, nausea, vomiting, abdominal pain, indigestion; with prolonged therapy - dysbiosis; rarely pseudomembranous colitis.

On the part of the organs of hematopoiesis: transient thrombocytopenia, leukopenia, neutropenia, pancytopenia, anemia, eosinophilia, hemolytic anemia, hemorrhage.

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

From the side of the cardiovascular system: tachycardia, chest pain.

Local Reactions: with intravenous injection - phlebitis, with intramuscular injection - hyperemia and soreness at the injection site.

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

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

Overdose:

It often occurs in patients with chronic renal failure.

Symptoms: convulsions, encephalopathy, neuromuscular excitation.

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

Interaction:

Solution Cefepime can 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 mixed 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.

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

With simultaneous use with aminoglycosides, synergism is manifested, 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 drug active against anaerobic microorganisms is recommended; drugs are administered 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 failure should regularly monitor the concentration of the drug in the blood.

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 500 mg.

Packaging:For 500 mg of active substance (cefepime) in bottles of clear, colorless glass, sealed with rubber stoppers, crimped with aluminum caps with protective plastic covers.For 1 bottle with instructions for use or 50 bottles along with 3-5 instructions for use in a cardboard pack.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children. List B.

Shelf life:2 years. Do not take it beyond the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008605/09

Date of registration:28.10.2009

Manufacturer: & nbsp

ORCHID CHEMICALS & PHARMACEUTICALS, Ltd. India

Representation: & nbspOrchid Chemicals and Pharmaceuticals Co., Ltd.Orchid Chemicals and Pharmaceuticals Co., Ltd.Russia

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Etipim® (Efepim®)