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 of the third 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 an penicillin-binding proteins.

It is active in vivo and in vitro for 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 ,. Pscudomonas aeruginosa. In vitro is active against gram positive aerobes: Staphylococcus epidermidis (methicillin-sensitive strains only), Staphylococcus saprophytics. Streptococcus agalactiae (group B); Gram-negative aerobes: Acinetobacter Iwoffii, 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 of Enterococcus, incl. Enterococcus faecalis, methicillin-resistant staphylococci, Stenotrophomonas maltophilia (formerly known as Xanthomonas maltophilia). Clostridium difficile is not sensitive to cefepime.

Pharmacokinetics:

Bioavailability of 100%. TSmax after intravenous and intramuscular injection at a dose of 0.5 g - by the end of infusion and 1-2 hours, respectively. Cmax at the / m introduction in doses of 0.5, 1 and 2 g - 14, 30 and 57 μg / ml, respectively; with / in the introduction of doses of 0.25, 0.5, 1 and 2 g - 18, 39, 82 and 164 μg / ml, respectively; time to reach the average therapeutic concentration in plasma - 12 h; the average therapeutic concentration for the / m administration is 0.2 μg / ml, with the w / in - 0.7 μg / ml.High concentrations are determined in urine, bile, peritoneal fluid, blister exudate, bronchial mucus secretion, sputum, prostate gland, appendix and gallbladder. The volume of distribution is 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%. 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. T1 / 2 with hemodialysis - 13 hours, with continuous peritoneal dialysis-19 hours.

Indications:

Infectious-inflammatory diseases caused by sensitive microorganisms.

- Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including 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 (methicillin-sensitive strains only). Streptococcus pyogenes.

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

Prevention of infections in the conduct of cavitary surgery.

Contraindications:

- hypersensitivity to cefepime or L-arginine, as well as to cephalosporin antibiotics, penicillins or other beta-lactam antibiotics;

- children age up to 2 months. (for intravenous administration);

- children under 12 years (for the / m introduction).

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

Pregnancy and lactation:The purpose of the drug during pregnancy is possible only in cases where the intended use for the mother exceeds the potential risk to the fetus. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration:

Intravenous (drip and jet) infuzionno (for at least 30 minutes) or intramuscularly (only with complicated or uncomplicated infections of urinary tract of mild and moderate severity caused by E. coli). Pneumonia (moderate to severe) caused by Streptococcus pneumoniae (including concomitant bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae or Enterobacter spp .: iv 1-2 g every 12 hours for 10 days.

Febrile neutropenia (empirical therapy): iv 2 g every 8 hours for 7 days or until neutropenia is resolved.Complicated or uncomplicated urinary tract infections of mild to moderate severity caused by E. coli, Klebsiella pneumoniae, Proteus mirabilis: iv or IM (only for E. coli infections) 0.5-1 g every 12 hours in within 7-10 days. Severe complicated or uncomplicated urinary tract infections (including pyelonephritis) caused by E. coli or Klebsiella pneumoniae: iv 2 g every 12 hours for 10 days.

Moderately severe and severe skin and soft tissue infections caused by Staphylococcus aureus (methicillin-sensitive strains only), Streptococcus pyogenes: iv 2 g every 12 hours for 10 days. Complicated intra-abdominal infections (in combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis: iv 2 g every 12 h for 7-10 days. To prevent infection during surgical interventions on the abdominal organs: 60 minutes before the start of the surgical operation, 2 g of the drug is injected intravenously for 30 minutes. At the end of the infusion, add an additional 500 mg of metronidazole intravenously. Metronidazole solutions should not be administered concomitantly with cefepime. Infusion system before the introduction of metronidazole should be washed. During long (more than 12 hours) surgical operations 12 hours after the first dose, it is recommended to re-administer 2 g of the drug intravenously for 30 minutes, followed by the administration of 500 mg of metronidazole.

In children from 2 months 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 IV; with febrile neutropenia - 50 mg / kg every 8 hours. Duration of treatment as in adults.

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 / mn)	Recommended maintenance doses
>60	500 mg	1 g every	2 grams	2 grams
	every 12	12 h	every 12	every 8
	h (usual	(conventional	h	h
	vine.	dose,	(conventional	(conventional
	correction	correction	dose.	Dose,
	vines are not	The dose is not	correction	correction
	required)	required)	vines are not	doses of HC
			required)	required)
30-60	500 mg every 2-1 h	1 g every 24 hours h	2 grams every 24 hours h	2 grams every 12 h
	500 .mg	500 mg	1 g	2 grams every 24 hours h
11-29	every 24 hours	every 24 hours	every 24 hours
	h	h	h
< 11	250 m g	250 mg	500 mg	1 g every 24 hours h
	every 24 hours	every 24 hours	every 24 hours
	h	h	h

With continuous ambulatory peritoneal dialysis, the recommended maintenance doses are 500 mg every 48 hours, 1 g every 48 hours, 2 g every 48 hours,2 g every 48 hours; patients on hemodialysis - 1 g on the first day of treatment, then 500 mg every 24 hours for all infections, with the exception of febrile neutropenia, where the dose is 1 g every 24 g. On hemodialysis days, the drug should be injected at the end of hemodialysis. If possible, the drug should be administered at the same time every day.

Data on the use of the drug in children with concomitant chronic renal failure are not available, however, given the similar pharmacokinetics in children and adults, the dosage regimen (dose reduction or increase in the interval between administrations) in children with CRF is similar to that for adults. Dose adjustments for patients with impaired liver function are not required. To prepare a solution for intravenous administration, the preparation is dissolved in 5 ml (0.5 g) or 10 ml (1.0 g, 2.0 g) of sterile water for injection, 5% solution of dextrose or 0.9% solution of sodium chloride . Intravenously injected intravenously for 3-5 minutes. For intravenous infusion, the prepared solution is combined with other solutions for intravenous infusions (0.9% sodium chloride solution, 5% or 10% dextrose solution, Ringer's solution with lactate and 5% dextrose solution, maximum concentration 40 mg / ml) and injected for not less than 30 minutes.To prepare a solution for intravenous administration, the preparation is dissolved in sterile water for injection, 0.9% solution of sodium chloride, bacsristiostatic water for injection with paraben or benzyl alcohol, in 0.5% and 1% solution of lidocaine hydrochloride (0.5 g in 1.5 ml, 1.0 g in 3.0 ml).

Side effects:

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

Local reactions: with iv introduction - phlebitis, with v / m - hyperemia, tenderness and inflammation at the injection site.

From the nervous system: headache, dizziness, paresthesia, confusion, convulsions,

encephalopathy (in the absence of dose adjustment in patients with impaired renal function).

From the genitourinary system: vaginitis, vaginal infections, genital itching.

From the urinary system: impaired renal function (toxic nephropathy, kidney failure).

From the digestive system: diarrhea, nausea, vomiting, constipation, abdominal pain, dyspepsia, pseudomembranous colitis.

From the hematopoiesis: anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, agranulocytosis,

hemolytic anemia, aplastic anemia, bleeding.

From the cardiovascular system: tachycardia, dyspnea, peripheral edema, vasodilation.

Laboratory indicators: decreased hematocrit, increased prothrombin time, increased partial thromboplastin time, increased concentration urea, hyperkreatinemia, hypercalcemia, increased activity of "liver" transaminases and alkaline phosphatase, hyperbilirubinemia.

Other: development of superinfection, oropharyngeal candidiasis, candidiasis, taste change.

Post-registration experience: encephalopathy (impaired consciousness, including confusion, hallucinations, stupor and coma), myoclonus, seizures and non-convulsive status epilepticus. Despite the fact that most cases were observed in patients with renal failure who received cefepime in doses higher than recommended, in some cases, neurotoxicity was noted in patients who underwent dose adjustment depending on the degree of renal failure.

Overdose:

Symptoms (often occur in patients with CRF): convulsions, encephalopathy, neuromuscular excitation.

Treatment: hemodialysis, maintenance therapy.

Interaction:

Pharmaceutically incompatible with other antimicrobial drugs and heparin.

Diuretics, aminoglycosides, polymyxin B reduce the tubular secretion of cefepime and increase its serum concentration, extend T1 / 2, increase nephrotoxicity (increases the risk of developing nephronecrosis). Cefepim increases the ototoxicity of aminoglycosides.

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 the solution of metronidazole (before the administration of the solution of metronidazole for the prevention of infections during surgical interventions, the infusion system should be rinsed from the solution of cefepime).To avoid possible drug interactions with other drugs, cefepime solutions (like most other beta-lactam antibiotics) should not be administered concomitantly with solutions of vancomycin, gentamicin, tobramycin, netilmicin. When prescribing cefepime with the listed drugs, each antibiotic should be administered separately.

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. Mild forms of colitis do not require special treatment, it is sufficient to stop the introduction of the drug; mild or severe cases may require special treatment. Possible cross-over hypersensitivity in patients with allergic reactions to penicillins. 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 from

confirmed for the given situation by clinical efficiency. Possible detection of a positive Coombs test, a false positive glucose test at urine.

During post-registration follow-up, the following serious adverse reactions were recorded, including life-threatening or fatal events: encephalopathy (impaired consciousness, confusion, hallucinations, stupor and coma), myoclonus, seizures and anonzodorozhne status (see " Side effect ": Post-registration experience). Most cases were noted in patients with renal insufficiency, who did not undergo dose adjustment. Nevertheless, in some cases, neurotoxicity was noted in patients who underwent dose adjustment depending on the degree of renal failure. In most cases, the symptoms of neurotoxicity were reversible and disappeared after drug withdrawal and / or after hemodialysis.If neurotoxicity is associated with the use of cefepime, consideration should be given to discontinuing cefepime therapy or adjusting the dose in patients with renal insufficiency.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection 0.5 g, 1.0 g, 2.0 g.

Packaging:0.5 g, 1.0 g and 2.0 g active substance in a clear glass vial sealed with a rubber stopper, crimped with an aluminum cap. Each vial with instructions for use is placed in a cardboard box.

Storage conditions:

List B.

In dry, 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 the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-010038/09

Date of registration:09.12.2009

The owner of the registration certificate:Sanjivani Parantaral Co., Ltd.Sanjivani Parantaral Co., Ltd. India

Manufacturer: & nbsp

SANJIVANI PARANTERAL, Limited India

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Cefepim (Cefepime)