Цедекс®

General characteristics. Structure:

Active ingredient: 144 mg of a tseftibuten (in the form of a dihydrate) in 1 g of powder or 36 mg in 1 ml of ready suspension.

Excipients: polysorbate 80, симетикон, gum xanthane, silicon dioxide, titanium dioxide, Natrium benzoicum, fragrance cherry, sucrose.

Pharmacological properties:

Pharmacodynamics. Generation cephalosporin III. Is beta лактамным an antibiotic, has bactericidal effect which mechanism is caused by suppression of synthesis of a cell wall of bacteria. Drug affects many microorganisms producing β-lactamelements and steady against penicillin and other cephalosporins.

Tseftibuten высокоустойчив to plasmid penicillinases and tsefalosporinaza. However it collapses under the influence of some chromosomal цефалоспориназ which are produced by such mikrorganizm as Citrobacter spp., Enterobacter spp. and Bacteroides spp. Drug should not be used at the infections caused by strains of bacteria which resistance to a beta laktamnym to antibiotics is caused by the general mechanisms, such as changes of permeability or the penicillin-the connecting proteins (PCP) (for example, penitsillinorezistentny Streptococcus pneumoniae). Tseftibuten interacts generally with PSB-3 of Escherichia coli that leads to formation of filamentozny forms at concentration, a component 1/4-1/2 MPK, and to a lysis at the concentration twice exceeding MPK. The minimum bactericidal concentration of a tseftibuten for strains of Escherichia coli sensitive and steady against ampicillin, is approximately equal to MPK.

in vitro and in clinical practice concerning the majority of strains of the following gram-positive microorganisms is active: Streptococcus pyogenes, Streptococcus pneumoniae (except for penitsillinorezistentny strains); gram-negative microorganisms: Haemophilus influenzae (the strains which are producing and not producing β-lactamelements), Haemophilus parainfluenzae (the strains which are producing and not producing β-lactamelements), Moraxella (Branhamella) catarrhalis (the majority of strains produce β-lactamelements), Escherichia coli, Klebsiella spp. (including Klebsiella pneumoniae and oxytoca), an indole - positive Proteus spp. (including Proteus vulgaris), and also Providencia spp., Proteus mirabilis, Enterobacter spp. (including Enterobacter cloacae and Enterobacter aerogenes), Salmonella spp., Shigella spp.

in vitro concerning the majority of strains of the following microorganisms is active, however clinical performance it is not established: gram-positive microorganisms - Streptococcus spp. C and G groups; gram-negative microorganisms - Brucella spp., Neisserria spp., Aeromonas hydrophilia, Yersinia enterocolitica, Providencia rettgeri, Providencia stuartii and strains of Citrobacter spp., Morganella spp. and Serratia spp., which do not develop chromosomal tsefalosporinaza in large numbers.

It is not active concerning Staphylococcus spp., Enterococcus spp., Streptococcus spp. groups B, Acinetobacter spp., Bordetella spp., Listeria spp., Flavobacterium spp., Pseudomonas spp., Campylobacter spp., Yersinia spp., Hafnia spp.

It is poorly active concerning the majority of anaerobe bacterias, including the majority of strains of Bacteroides.

Tseftibuten-trans (derivative a tseftibutena) has no microbiological activity of in vitro and in vivo concerning Staphylococcus spp., Enterococcus spp., Acinetobacter spp., Bordetella spp., Listeria spp., Flavobacterium spp., Pseudomonas spp., Campylobacter spp., Yersinia spp., Hafnia spp.

Pharmacokinetics. Absorption. After administration of drug inside цефтибутен it is almost completely absorbed from a GIT (90%).

After a single dose in capsules on 400 mg of Cmax in plasma it is reached in 2-3 h and makes 15-17 mkg/ml.

Bioavailability of a tseftibuten depends on a dose in the therapeutic range of doses (≤400 mg) and varies from 75% to 94%.

Speed and extent of absorption of a tseftibuten at Tsedeks's reception in the form of suspension change at a concomitant use with food. The concomitant use of food does not influence Tsedeks's efficiency in the form of capsules.

Distribution. Linkng of a tseftibuten with proteins of plasma is made by 62-64%. Css of a tseftibuten (at reception each 12 h) in plasma are reached after reception of the fifth dose.

Tseftibuten easily gets into fluid mediums and body tissues. In liquid of a skin bubble concentration of a tseftibuten is comparable to that in plasma or exceeds it (comparison on the basis of AUC). Tseftibuten gets into liquid of a middle ear at children with acute average otitis where its concentration is approximately equal to level in plasma or exceeds it. Concentration of a tseftibuten in tissue of lungs make about 40% of concentration in plasma. In a nasal, tracheal and bronchial secret, bronchoalveolar lavazhny liquid and its cellular suspension of concentration of a tseftibuten make about 46, 20, 24, 6 and 81% of concentration in plasma respectively.

There are no adequate data on concentration of a tseftibuten in cerebrospinal liquid, however at reception of other cephalosporins in their content in cerebrospinal liquid usually does not reach therapeutic level.

Metabolism and removal. The basic derivative a tseftibutena, circulating in plasma (tseftibuten-trance), apparently, is formed by direct transformation of a tseftibuten (cis-forms). Concentration a tseftibutena-trance in plasma or urine usually makes about 10% or less from concentration of a tseftibuten.

T1/2 of a tseftibuten makes from 2 to 4 h of plasma (on average 2.5 h) and does not depend on a dose or the scheme of use. It is removed generally in not changed view with urine. Tseftibuten is found in urine during 24 h after reception of 400 mg; Cmax in urine makes 264 mkg/ml and is reached during the first 4 h; in 20-24 h after a single dose of drug concentration of a tseftibuten in urine makes 10.5 mkg/ml.

Pharmacokinetics in special clinical cases. At elderly people of Css of a tseftibuten (at reception each 12 h) are reached after reception of the fifth dose. Average AUC in this group was slightly higher, than at young adults. At repeated use of a tseftibuten for elderly people cumulation was insignificant.

At a renal failure of easy severity Tsedeks's pharmacokinetics significantly does not change.

Indications to use:

Treatment of the infectious and inflammatory diseases caused by sensitive microorganisms:

— upper respiratory tract infections (including pharyngitis, tonsillitis and scarlet fever at adults and children, acute sinusitis at adults);

— average otitis at children;

— lower respiratory tract infections at adults (including an acute bronchitis, an exacerbation of chronic bronchitis and an acute pneumonia) when administration of drug inside is possible;

— infections of urinary tract at adults and children (including complicated and uncomplicated);

— the enteritis and a gastroenteritis at children caused by Salmonella spp., Shigella spp. and Escherichia coli.

Route of administration and doses:

Accept inside. Duration of treatment averages from 5 to 10 days. At treatment of the infections caused by Streptococcus pyogenes, it is necessary to apply Tsedeks® in a therapeutic dose not less than 10 days.

Adults. The recommended dose makes 400 mg/days of Tsedeks® in capsules it is possible to accept irrespective of meal. At acute bacterial sinusitis, an acute bronchitis, an exacerbation of chronic bronchitis and the complicated and uncomplicated infections of urinary tract it is possible to use drug in a dose 400 mg of 1 times/days.

At community-acquired pneumonia and a possibility of administration of drug inside the recommended Tsedeks's dose makes 200 mg each 12 h. Duration of therapy makes 5-10 days depending on severity and a type of a disease.

At a renal failure change of a dose is required only at decrease in KK less than 50 ml/min. At KK of 30-49 ml/min. the daily dose should be lowered to 200 mg; at KK of 5-29 ml/min. the recommended daily dose makes 100 mg. If change of frequency rate of use is preferable, then at KK of 30-49 ml/min. Tsedeks® in a dose of 400 mg it is possible to appoint each 48 h, at KK of 5-29 ml/min. - each 96 h (in 3 days).

To the patients receiving treatment by a hemodialysis 2 or 3 times a week, it is possible to appoint Tsedeks® on 400 mg at the end of each session of a hemodialysis.

Children. The recommended drug dose in the form of suspension makes 9 mg/kg/days. The maximum dose - 400 mg/days. At pharyngitis (including with tonsillitis), acute purulent average otitis and infections of uric ways (including complicated) it is possible to use drug 1 times/days.

At acute bacterial enteritis at children the daily dose can be divided into 2 receptions (at the rate of 4.5 mg/kg each 12 h).

Children with body weight more than 45 kg or at the age of more than 10 years can appoint drug in the dose recommended for adults.

Safety and Tsedeks's efficiency at children aged up to 6 months are not established.

Tsedeks's suspension can be taken approximately for 1-2 h to or after food. Before administration of drug the bottle with the prepared suspension should be stirred up intensively.

Rules of preparation of suspension for intake. To measure a necessary amount of water (28 ml), having poured water in a measured glass (is included in the delivery package) to a tag of "28 ml". To pour about a half of the measured water in a bottle with powder and to shake up well to moisten powder, then to add the remained amount of water in a bottle and once again carefully to shake up — before full dissolution of powder and receiving 33 ml of homogeneous suspension. For more exact dosing of the prepared suspension it is recommended to use the measured spoon which is included in the package and having graduation on 1,25 ml, 2,5 ml, 3,75 ml and 5 ml of suspension.

Features of use:

Use at pregnancy and feeding by a breast. Adequate and strictly controlled researches of safety and efficiency of use of drug at pregnancy and at the time of delivery were not conducted. In need of use of the drug Tsedeks® at pregnancy it is necessary to estimate estimated advantage for mother and potential risk for a fruit.

Tseftibuten is not defined in breast milk at the feeding women. With care it is necessary to use drug during breastfeeding.

In pilot studies on animals the damaging action of a tseftibuten on the course of pregnancy or childbirth, on embryonic or post-natal development is not revealed.

Use at renal failures. Change of a dose is required to adult patients at a renal failure only at decrease in KK less than 50 ml/min. At KK from 49 to 30 ml/min. the daily dose should be lowered to 200 mg or to appoint 400 mg each 48 h (every other day); at KK from 29 to 5 ml/min. the recommended daily dose makes 100 mg or drug is appointed on 400 mg by each 96 h (in 3 days). At the patients receiving a hemodialysis 2 or 3 times a week, it is possible to appoint Tsedeks on 400 mg at the end of each session of a hemodialysis.

Use for children. It is contraindicated at children's age up to 6 months, at children's age up to 10 years (in connection with impossibility of an adequate drug dosing of Tsedeks® in the form of capsules at children of younger age).

Special instructions. Approximately at 5% of patients with an allergy to penicillin cross-responsiveness on cephalosporins is observed. At the patients receiving at the same time penicillin and cephalosporins serious acute reactions of hypersensitivity are registered (anaphylaxis); cases of cross hyperreactivity with development of an anaphylaxis are known. At emergence of serious anaphylactic reactions emergency treatment is shown (for example, Epinephrinum, GKS, in/in administration of liquid, ensuring passability of respiratory tracts, administration of oxygen, antihistamines, dynamic observation).

At treatment by antibiotics of a broad spectrum of activity (including Tsedeksom) disturbance of intestinal microflora can lead to emergence of diarrhea, including the pseudomembranous colitis connected with production of Clostridium difficile toxin. Expressiveness of the diarrhea which is followed or not followed by dehydration can vary from moderate to heavy or life-threatening. Diarrhea can develop in time or after treatment by an antibiotic. This diagnosis needs to be discussed in all cases when persistent diarrhea develops against the background of reception of any antibiotic of a broad spectrum of activity like Tsedeks.

Tsedeks's influence on results of chemical or laboratory tests is not revealed. When using other cephalosporins sometimes registered false positive direct test of Koombs. However results of researches with use of erythrocytes of healthy people did not confirm Tsedeks's ability to cause positive test of Koombs of in vitro even in concentration to 40 mkg/ml.

Side effects:

From the alimentary system: nausea (≤3%), diarrhea (3%); infrequently - dyspepsia, gastritis, vomiting, abdominal pains, taste change; seldom - increase in activity of nuclear heating plant, ALT and LDG, Clostridium difficile growth combined with the moderated or expressed diarrhea.

From a nervous system: headache (2%); infrequently - dizziness, drowsiness; very seldom - spasms.

From system of a hemopoiesis: seldom - decrease in level of hemoglobin, a leukopenia, an eosinophilia, a thrombocytosis.

Others: infrequently - the symptoms similar to those at a serum disease.

The majority of the undesirable phenomena connected with Tsedeks's reception are usually moderately expressed and is passing, give in to symptomatic therapy or pass after Tsedeks's cancellation.

Side effects inherent to all cephalosporins

Allergic reactions: anaphylaxis, bronchospasm, short wind, rash, urticaria, itch, Quincke's disease, Stephens-Johnson's syndrome, mnogoformny erythema, toxic epidermal necrolysis.

From the alimentary system: the expressed diarrhea, the colitis (connected with treatment by antibiotics including pseudomembranous colitis), increase in level of bilirubin.

From system of a hemopoiesis: aplastic anemia, pancytopenia, neutropenia and agranulocytosis.

From coagulant system of blood: increase in a prothrombin time and MHO, hemolitic anemia and internal bleeding.

From an urinary system: dysfunction of kidneys, toxic nephropathy.

Laboratory indicators: positive reaction of Koombs, glucosuria, ketonuria.

Others: superinfection, photosensitization.

Interaction with other medicines:

In special researches interaction of the drug Tsedeks® with the following drugs was studied: the antacids containing aluminum hydroxide and magnesium in high doses, ranitidine and theophylline (single in/in introduction). Signs of significant interaction are not revealed. Influence of the drug Tsedeks® on concentration in a blood plasma or theophylline pharmacokinetics at intake is not known. Data on interaction with other medicines are not obtained so far.

Cephalosporins, including Tsedeks®, in rare instances can reduce prothrombin activity that leads to increase in a prothrombin time, especially at patients who were stabilized on therapy by peroral coagulants. At the patients belonging to risk group it is regularly necessary to control a prothrombin time or MNO and if necessary to apply vitamin K.

Contraindications:

— children's age up to 6 months;

— children's age up to 10 years (in connection with impossibility of an adequate drug dosing of Tsedeks® in the form of capsules at children of younger age);

— hypersensitivity to components of drug and to other cephalosporins.

With care patients should appoint drug with the known or estimated allergy to penicillin; with the complicated gastrointestinal diseases, especially chronic colitis (in the anamnesis), and also with the expressed renal failure and to the patients who are on a hemodialysis.

Overdose:

At accidental overdose of Tsedeks signs of toxicity were not noted. The healthy adult volunteers receiving Tsedeks® once in a dose to 2 g, had no serious undesirable reactions, and all clinical and laboratory indicators remained within norm.

Treatment: the specific antidote of a tseftibuten does not exist therefore at overdose it is possible to carry out a gastric lavage. A considerable part of a dose of Tsedeks can be removed from blood by means of a hemodialysis. Efficiency of peritoneal dialysis is not established.

Storage conditions:

Capsules should be stored at a temperature not above 25 °C. Powder for preparation of suspension for intake should be stored in the dry, protected from light place at a temperature not above 25 °C. A period of validity - 2 years. The prepared suspension can be stored within 14 days in the refrigerator (at a temperature from 2 °C to 8 °C). Drug should be stored in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

8.3 - bottles of dark glass with a capacity of 30 ml (1) complete with a measured spoon and a measured glass - packs cardboard.