Tsefepim
Producer: CJSC Pharmaceutical Firm LEKKO Russia
Code of automatic telephone exchange: J01DE01
Release form: Liquid dosage forms. Powder for preparation of solution for injections.
General characteristics. Structure:
Active ingredient - a tsefepima a hydrochloride (in terms of tsefepy) - 1,0 g; Excipient – arginine
Description: powder of color, white or white with a yellowish shade
Pharmacological properties:
Pharmacodynamics. Antibacterial agent from group of cephalosporins IV of generation. Works bakteritsidno, breaking synthesis of a cell wall of microorganisms. Possesses a broad spectrum of activity concerning gram-positive and gram-negative bacteria, strains, resistant to aminoglycosides and/or tsefalosporinovy antibiotics of the III generation. Высокоустойчив to hydrolysis of the majority beta лактамаз and quickly gets into gram-negative bacterial cells. In a bacterial cell a molecular target is penicillin - the connecting proteins. in vitro concerning the following microorganisms is active:
- gram-positive aerobes, such as Staphylococcus aureus and Staphylococcus epidermidis (including the strains producing beta lactamazu), Staphylococcus hominis, Staphylococcus saprophyticus, other strains of Staphylococcus spp., Streptococcus pyogenes (group A), Streptococcus agalactiae (group B), Streptococcus pneumoniae, other beta and hemolitic Streptococcus spp. (C, G groups and F), Streptococcus bovis (group D), Streptococcus viridans;
- gram-negative aerobes, such, kakPseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas putida ipseudomonas 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. (including 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 the strains producing beta lactamazu), Haemophilus parainfluenzae, Hafnia alvei, Legionella spp. Morganella morganii, Moraxella catarrhalis (including the strains producing beta lactamazu), Neisseria gonorrhoeae (including the strains producing beta lactamazu), Neisseria meningitides, Providencia spp. (including Providencia rettgeri, Providencia stuartii), Salmonella spp., Serratia spp. (including Serratia marcescens, Serratia liquefaciens), Shigella spp., Yersinia enterocolitica;
- anaerobe bacterias, such as Prevotella spp. (including Prevotella melaninogenicus), Clostridium perfringens, Fusobacterium spp., Mobiluncus spp., Peptostreptococcus spp., Veillonella spp., Bacteroides spp. (including Bacteroides melaninogenicus and another, relating to Bacteroides microorganisms of an oral cavity).
Resistance. To a tsefepim pneumococci, resistant to penicillin, some strains of Xanthomonas maltophilia, the majority of strains of enterococci, including Enterococcus faecalis are steady Bacteroides fragilis, Clostridium difficile, staphylococcus, resistant against Methicillinum.
Pharmacokinetics. Bioavailability of a tsefepim of 100 %. Average concentration in a blood plasma at adults through different time after single 30-minute infusion of 1,0 g of a tsefepim, the maximum concentration (Cmax) and the area under a curve "concentration time" (AUC) are presented in table 1.
The average volume of distribution is equal to 0,25 l/kg; children from 2 months to 16 years have 0,33 l/kg.
About 20 % of the entered dose contact proteins of a blood plasma.
High concentration are defined in urine, bile, peritoneal liquid, blister exudate, a mucous membrane of bronchial tubes, a phlegm, a prostate, an appendix and a gall bladder.
The elimination half-life makes 2 h; at a hemodialysis – 13 h, at continuous peritoneal dialysis – 19 h.
About 15 % of a dose are metabolized in a liver and kidneys, and about 85 % are removed with urine in an invariable look.
Indications to use:
- the pneumonia (medium-weight and heavy) caused by Streptococcus pneumoniae (including cases of association with the accompanying bacteremia), Pseudomonas aeruginosa, Klebsiella pneumoniae ilienterobacter spp.
- febrile neutropenia (empirical therapy).
- the complicated and uncomplicated infections of urinary tract (including pyelonephritis) caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis.
- the uncomplicated infections of skin and soft tissues caused by Staphylococcus aureus (only metitsillinochuvstvitelny strains), Streptococcus pyogenes.
- the complicated intraabdominal infections (in a combination with metronidazole) caused by Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp., Bacteroides fragilis.
Route of administration and doses:
Enter intravenously (struyno, kapelno) or intramusculary (only at the complicated or uncomplicated infections of urinary tract of the easy and moderately severe, caused Escherichia coli).
The dose and way of introduction depend on localization, character and type of an infection, function of kidneys and age of the patient.
Adults. In table 3 the recommended doses, ways of introduction and duration of therapy depending on character and localization of an infection are specified.
Table 3
|
Character and localization of an infection
|
Single dose, way and frequency of introduction
|
Duration of therapy (days)
|
|
Medium-weight and heavy pneumonia
|
1,0 - 2,0 g intravenously each 12 h
|
10
|
|
The medium-weight uncomplicated and complicated infections of kidneys and urinary tract, including pyelonephritis
|
0,5 - 1,0 g intravenously or intramusculary each 12 h
|
7 - 10
|
|
The heavy uncomplicated and complicated infections of kidneys and urinary tract, including pyelonephritis
|
2,0 g intravenously each 12 h
|
10
|
|
The complicated intraabdominal infections (in a combination with metronidazole)
|
2,0 g intravenously each 12 h
|
7 - 10
|
|
Medium-weight and heavy uncomplicated infections of skin and soft tissues
|
2,0 g intravenously each 12 h
|
10
|
|
Neytropenichesky fever; zhizneugrozhayushchy infection
|
2,0 g intravenously each 8 h
|
7
|
Patients with an abnormal liver function. Patients of this category do not have need to reduce a dose of a tsefepim.
Patients with a renal failure. The dosing modes recommended usually for patients with normal function of kidneys, with a renal failure and for the patients who are on peritoneal dialysis or a hemodialysis are presented in table 4.
Table 4
|
Clearance of creatinine
(ml/min.)
|
Single dose and frequency of introduction
|
||||
|
1
|
2
|
3
|
4
|
5
|
|
|
> 60 (normal function of kidneys)
|
0,5 g each 12 h
|
1,0 g each 12 h
|
2,0 g each 12 h
|
2,0 g each 8 h
|
|
|
1
|
2
|
3
|
4
|
5
|
|
|
30-60
|
0,5 g each 24 h
|
1,0 g each 24 h
|
2,0 g each 24 h
|
2,0 g each 12 h
|
|
|
11-29
|
0,5 g each 24 h
|
0,5 g each 24 h
|
1,0 g each 24 h
|
2,0 g each 24 h
|
|
|
<11
|
0,25 g each 24 h
|
0,25 g each 24 h
|
0,5 g each 24 h
|
1,0 g each 24 h
|
|
|
Peritoneal dialysis
|
0,5 g each 48 h
|
1,0 g each 48 h
|
2,0 g each 48 h
|
2,0 g each 48 h
|
|
|
Hemodialysis
|
1,0 g in the first day of a hemodialysis, further 0,5 g each 24 h
|
1,0 g each 24 h
|
|||
The patients who are on a hemodialysis tsefepy should enter after the termination of a hemodialysis, it is desirable at the same time.
Children from 2 months to 16 years. At children from 2 months to 16 years and with body weight to 40 kg the recommended dosing mode according to all indications (excepting a febrile neutropenia) – 50 mg/kg each 12 h intravenously; at a febrile neutropenia – 50 mg/kg each 8 h. Treatment duration as at adults.
Intravenous administration.
Struyno: drug with a dosage of 1,0 g is dissolved in 10 ml of sterile water for injections or 5% of solution of a dextrose (glucose), or by 0,9% of solution of sodium of chloride (table 5); enter within 3-5 min.
Kapelno (within not less than 30 min.): for intravenous drop administration drug dissolve in the small volume (5-10 ml) of one of following solutions - 0,9 % solution of sodium chloride, 5 % or 10 % solution of a dextrose (glucose), lactate sodium solution, mix of 5 % of solution of a dextrose and 0,9 % of solution of sodium chloride, mix of a lactate of Ringer and 5 % of solution of a dextrose, and bring volume the same solution to 50 ml or 100 ml (table 5); enter within not less than 30 min.
During infusion it is recommended to suspend administration of other solutions.
Intramuscular introduction. Drug a dosage of 1,0 g is dissolved in 2,4 ml of sterile water for injections or 0,9 % of solution of sodium chloride, or by 0,5-1% of solution of lidocaine of a hydrochloride (table 5); enter deeply into a muscle, for example, in an upper outside quadrant of a buttock.
At an intramuscular injection it is necessary to carry out preliminary aspiration to exclude hit of a needle in a vessel and not to allow administration of solution, especially lidocaine, in blood!
Solution preparation. Solvent volumes depending on a necessary dosage and a way of introduction, and also the received approximate concentration of drug are presented in table 5.
Table 5
|
Dosage and way of introduction
|
Solvent volume
(ml)
|
The approximate taken volume (ml)
|
Approximate concentration of drug (mg/ml)
|
|
Intravenous administration (struyno)
|
|||
|
1,0 g
|
10,0
|
11,3
|
100
|
|
Intravenous administration (kapelno)
|
|||
|
1,0 g
|
50,0
|
50,0
|
20
|
|
1,0 g
|
100,0
|
100,0
|
10
|
|
Intramuscular introduction
|
|||
|
1,0 g
|
2,4
|
3,6
|
280
|
The received solution should not contain any particles!
The prepared drug solutions for intravenous and intramuscular injections store no more than 24 p at the room temperature or within no more than 7 days in the refrigerator at a temperature of 2-8 ° C. Darkening of solution does not demonstrate change of activity of drug.
Features of use:
At suspicion of an aerobic-anaerobic infection – before identification of the activator, additional purpose of antibacterial drug, active concerning anaerobic microorganisms is recommended; the drugs have to be administered separately!
To patients at whom dissimination from the center of an infection is possible and there is a suspicion of meningitis, it is necessary to appoint an alternative antibiotic with clinically confirmed efficiency at meningitis.
In case of development of pseudomembranous colitis drug is cancelled; medium-weight and heavy forms of a complication demand purpose of Vancomycinum or metronidazole.
Cross hypersensitivity at patients with allergic reactions to penicillin is possible. In case of allergic reaction use of drug is stopped; serious reaction of immediate type can demand introduction of Epinephrinum, a glucocorticoid and carrying out other urgent measures.
At a heavy renal/liver failure it is regularly necessary to control concentration of drug in blood.
Lasting treatment more than 10 days is necessary regular control of indicators of blood and a functional condition of a liver and kidneys.
Side effects:
Allergic reactions: skin rash (including an erythema), an itch, fever, anaphylactoid reactions, an eosinophilia, a multiformny exudative erythema (including Stephens-Johnson's syndrome), it is rare – a toxic epidermal necrolysis (Lyell's disease).
From a nervous system: headache, dizziness, sleeplessness, paresthesias, feeling of concern, confusion of consciousness, spasm.
From urinogenital system: vaginitis.
From an urinary system: extremely seldom - a renal failure, a toxic nephropathy.
From digestive tract: diarrhea, nausea, vomiting, locks, abdominal pain, dyspepsia; at long therapy – dysbacteriosis; extremely seldom - a pseudomembranous coloenteritis.
From bodies of a hemopoiesis: anemia, tranzitorny thrombocytopenia, a leukopenia, a neutropenia, a pancytopenia, hemolitic anemia, the raised bleeding.
From CCC: tachycardia, stethalgias.
Local reactions: at intravenous administration – phlebitis, at intramuscular introduction – a hyperemia and morbidity in an injection site.
Laboratory indicators: decrease in a hematocrit, increase in a prothrombin time, increase in concentration of urea, a giperkreatininemiya, a hypercalcemia, increase in activity of "hepatic" transaminases and alkaline phosphotazy, a hyperbilirubinemia, positive direct test of Koombs, false positive test on urine glucose.
Others: a pharyngalgia, the increased sweating, dorsodynias, an adynamy, peripheral hypostases, candidiasis.
Interaction with other medicines:
Solution of a tsefepim cannot be mixed with solutions of metronidazole, Vancomycinum, gentamycin, Tobramycinum, netilmitsin, Aminophyllinum. If necessary these solutions enter separately.
Solution of drug can be added to ampicillin solution if concentration of each of the mixing solutions does not exceed 40 mg/ml.
Diuretics, aminoglycosides and polymyxin B reduce canalicular secretion of a tsefepim, extend an elimination half-life, increase concentration of drug in blood; increase nephrotoxicity.
Non-steroidal anti-inflammatory drugs slow down removal of cephalosporins and increase risk of development of bleeding.
At simultaneous use with aminoglycosides shows a synergism, with macroleads, chloramphenicol or tetracyclines – antagonism.
Contraindications:
Hypersensitivity to a tsefepim and others a beta - to laktamny antibiotics, including cephalosporins, penicillin, karbapenema, monobaktama; hypersensitivity to arginine; I trimester of pregnancy; children's age up to 2 months.
With care. The patient with a renal failure; at nonspecific ulcer colitis, including in the anamnesis; to children up to 12 years in connection with the insufficient number of the conducted researches.
Pregnancy and period of a lactation. Use in II and III trimesters of pregnancy is possible only if the estimated advantage for mother exceeds potential risk for a fruit.
Tsefepim is allocated with breast milk therefore breastfeeding should be stopped in case of administration of drug.
Overdose:
Arises at patients with a chronic renal failure more often.
Symptoms: spasms, encephalopathy, neuromuscular excitement.
Treatment: at a renal failure – a hemodialysis; careful observation and a maintenance therapy at normal functioning of kidneys.
Storage conditions:
List B. In the place protected from light at a temperature not over 30 of 0C. To store in the place, unavailable to children.
Issue conditions:
According to the recipe
Packaging:
Powder for preparation of solution for intravenous and intramuscular administration of 1,0 g.
On 1,0 g in bottles polymeric or glass.
On 1 bottle with the application instruction in a pack from a cardboard.
On 5 or 30 bottles with the application instruction in a box from a cardboard.
