Cedex

Active material: Tseftybuten
When ATH: J01DD14
CCF: III generation cephalosporins
ICD-10 codes (testimony): A02, A03, A04.0, A38, H66, J01, J02, J03, J04, J15, J20, J31, J32, J35.0, J37, J42, N10, N11, N30, N34, N41
When CSF: 06.02.03
Manufacturer: S.I.F.I. S.p.A. (Italy)

Pharmaceutical form, composition and packaging

Capsules white or yellowish white; contents of capsules – powder white or yellowish.

Excipients: microcrystalline cellulose, sodium starch glycolate, magnesium stearate.

Ingredients of the capsule shell: sodium lauryl, Titanium dioxide, gelatin.

1 PC. – bags (5) – cardboard boxes.

Powder for oral suspension from light yellow to dark yellow; in water forming a pale yellow slurry with a characteristic odor cherry.

Excipients: xanthan gum, sucrose, simethicone, silicon dioxide, Titanium dioxide, polysorbate 80, Sodium benzoate, flavor with a cherry taste.

Dark glass bottles capacity 30 ml (1) complete with a dosing spoon and measuring cup – packs cardboard.
Dark glass bottles capacity 60 ml (1) complete with a dosing spoon and measuring cup – packs cardboard.

Pharmacological action

III generation cephalosporins. It is a beta-lactam antibiotic, It has a bactericidal effect, the mechanism of which is due to suppression of the synthesis of the bacterial cell wall. The drug acts on many microorganisms, producing β-lactamase and are resistant to penicillins and other cephalosporins.

Ceftibuten is highly resistant to penicillinases plasmid and cephalosporinase. However, it is destroyed by the action of certain chromosomal cephalosporinase, are produced such as the mikrorganizmami Citrobacter spp., Enterobacter spp. и Bacteroides spp. The drug should not be used for infections, caused by strains of bacteria, whose stability to beta-lactam antibiotics is due to common mechanisms, such as changes in permeability or penicillin-binding protein (PSB) (eg, пенициллинорезистентный Streptococcus pneumoniae). Ceftibuten interacts mainly with PSB-3 Escherichia coli, which leads to the formation of filamentous forms at concentration, component 1/4-1/2 IGC, and lysed at a concentration, twice the MIC. The minimum bactericidal concentration ceftibuten for Escherichia coli strains, sensitive and ampicillin resistant, approximately equal to the IPC.

Active in vitro and in clinical practice against most strains of the following Gram-positive microorganisms: Streptococcus pyogenes, Streptococcus pneumoniae (with the exception of penicillin-resistant strains); Gram-negative microorganisms: Haemophilus influenzae (strains, продуцирующих и не продуцирующих b-лактамазы), Haemophilus parainfluenzae (strains, продуцирующих и не продуцирующих b-лактамазы), Moraxella (Branham) catarrhalis (Most strains produce β-lactamase), Escherichia coli, Klebsiella spp. (including oxytoca and Klebsiella pneumoniae), индол-положительный Proteus spp. (включая Proteus vulgaris), а также Providencia spp., Proteus is wonderful, Enterobacter spp. (including Enterobacter cloacae and Enterobacter aerogenes), Salmonella spp., Shigella spp.

Активен in vitro against most strains of the following organisms, but its clinical efficacy has not been established; Gram-positive microorganisms: Streptococcus spp. Group C and G; Gram-negative microorganisms: Brucella spp., Neisserria spp., Aeromonas hydrophilia, Yersinia enterocolitica, Rettgeri Providence, Providencia stuartii and strains of Citrobacter spp., Morganella spp. и Serratia spp., which do not produce large quantities of chromosomal cephalosporinase.

Activity against Staphylococcus spp., Enterococcus spp., Acinetobacter spp., Listeria spp., Flavobacterium spp. и Pseudomonas spp., weakly active against most anaerobes, including most strains of Bacteroides.

Ceftibuten has no trans-microbial activity in vitro and in vivo against strains of the same.

Pharmacokinetics

Absorption

After taking the drug inside ceftibuten almost completely absorbed from the gastrointestinal tract (90%). In one study, C_max in plasma after a single oral administration in capsule form ceftibuten 200 mg averaged about 17 ug / ml. C_max plasma achieved through 2 and h 3 h after a single oral capsules 200 mg 400 mg.

Bioavailability ceftibuten dose dependent in the therapeutic dose range (≤400 mg). The rate and extent of absorption when taking ceftibuten Tsedeksa in suspension changed while receiving food. Simultaneous food intake does not affect the efficiency of Tsedeksa in the form of capsules.

Distribution

The degree of binding to plasma proteins ceftibuten low (62-64%). C_ss tseftybutena (upon receipt of each 12 no) in plasma are reached after receiving the fifth dose. A notable accumulation of the drug with repeated use is not marked.

It ceftibuten easily penetrate fluids and tissues. The fluid bladder skin ceftibuten concentration comparable to that of plasma or exceeds its (Comparison based on AUC). Ceftibuten enters the middle ear fluid of children with acute otitis media, wherein the concentration level is approximately equal to or greater than the plasma. Ceftibuten concentration in the lung tissue is approximately 40% plasma concentrations of. The nasal, tracheal and bronchial secretions, broncho-alveolar lavage fluid and its cell suspension ceftibuten concentration is approximately 46, 20, 24, 6 and 81% of plasma concentrations, respectively.

Adequate data on concentrations of ceftibuten in the cerebrospinal fluid is not, However, when taking into other cephalosporins their content in cerebrospinal fluid usually does not reach therapeutic levels.

Metabolism and excretion

The main derivative ceftibuten, circulating plasma (ceftibuten-trans), apparently, produced by direct conversion of ceftibuten (cis-form). Trans ceftibuten concentration in plasma or urine is usually about 10% or less of the concentration of ceftibuten.

T_1/2 ceftibuten from plasma is from 2 to 4 no (average 2.5 no) and does not depend on the dose or dosage schedule. Write mainly unchanged in the urine. Ceftibuten detected in the urine within 24 h after administration 400 mg; C_max in urine of 264 ug / ml and is achieved in the first 4 no; through 20-24 h after a single dose of the drug concentration in the urine of ceftibuten 10.5 ug / ml.

Pharmacokinetics in special clinical situations

In the elderly C_ss tseftybutena (upon receipt of each 12 no) achieved after administration of the fifth dose. The mean AUC in this group had slightly higher, than in young adults. Repeated use of ceftibuten in the elderly accumulation was negligible.

In renal insufficiency, mild pharmacokinetics Tsedeksa does not change.

Testimony

Treatment of infectious and inflammatory diseases, caused by susceptible microorganisms:

- Infections of the upper respiratory tract (incl. pharyngitis, tonsillitis and scarlet fever in adults and children, acute sinusitis in adults, otitis media in children);

- Infections of the lower respiratory tract in adults (incl. acute bronchitis, exacerbation of chronic bronchitis and acute pneumonia) where, where can receive the drug inside, ie. in community-acquired infections;

- Urinary tract infections in adults and children (incl. complicated and uncomplicated);

- Enteritis and gastroenteritis in children, вызванные Salmonella spp., Shigella spp. и Escherichia coli (ceftibuten not active against Campylobacter spp. и Yersinia spp.).

Dosage regimen

The duration of treatment on average by 5 to 10 days. In the treatment of infections, caused by Streptococcus pyogenes, Tsedeks therapeutic dose to be applied for at least 10 days.

To Adult The recommended dose is Tsedeksa 400 mg / day. Tsedeks capsules can be taken regardless of meals. At acute bacterial sinusitis, Ostrom bronchi, exacerbation of chronic bronchitis and complicated and uncomplicated urinary tract infections drug can be used in a dose of 400 mg 1 time / day.

At community-acquired pneumonia and the possibility of oral administration of the recommended dose Tsedeksa 200 mg every 12 no.

Adult patients at impaired renal function change in dose is required only with a decrease of less than CK 50 ml / min. At KK from 49 to 30 ml / min the daily dose should be reduced to 200 mg or appoint 400 mg every 48 no (in one day); at KK from 29 to 5 ml / min The recommended daily dose is 100 mg or drug prescribed for 400 mg every 96 no (through 3 day). Patients, receiving hemodialysis 2 or 3 times a week, Tsedeks can appoint 400 mg after each hemodialysis.

Babies preparation is preferably administered in the form of a suspension, The recommended dose is 9 mg / kg / day. The maximum dose – 400 mg / day. At faringite (incl. with tonsillitis), acute purulent otitis media and urinary tract infections (incl. Complicated) drug can be used 1 time / day.

At acute bacterial enteritis children the daily dose can be divided into 2 admission (calculated 4.5 mg / kg every 12 no).

Children weighing more 45 kg or more 10 years the drug can be administered at the recommended dose for adults.

The safety and efficacy Tsedeksa children under the age of 6 Months not set.

The suspension can be taken Tsedeksa around 1-2 hours before or after meals. Before taking this medication vial with the prepared suspension should shake vigorously.

Rules suspension for oral administration

Measure the amount of water (25 ml), pouring water into a measuring cup (included) up to the level of hole. Pour about half of the metered water into the vial of powder and shake, it is good to moisten the powder, then add the remainder of the water to the vial and again Shake - until complete dissolution of the powder and preparation 30 ml of a homogeneous suspension. For a more precise metering of the suspension was recommended to use the dosing spoon, the included and having grading on 45 mg, 90 mg, 135 mg 180 mg suspension.

Side effect

Adverse events, registered patients, who received Tsedeks

From the digestive system: nausea (≤3%), diarrhea (3%); rarely – dyspepsia, gastritis, vomiting, stomach ache, increased activity of AST, ALT and LDG; rarely – рост Clostridium difficile, combined with moderate or severe diarrhea.

CNS: headache, rarely – dizziness; rarely – convulsions.

From the hematopoietic system: rarely – decrease in hemoglobin, leukopenia, eozinofilija, thrombocytosis.

Most adverse events, associated with taking Tsedeksa, usually are mild and transient, amenable to symptomatic therapy or are canceling after Tsedeksa.

Adverse events, registered patients in the treatment of a variety of cephalosporins

Allergic reactions: anaphylaxis, bronchospasm, breathlessness, rash, hives, increased sensitivity reactions, itch, angioedema, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis.

From the digestive system: severe diarrhea, colitis (associated with treatment with antibiotics, including pseudomembranous colitis), increased levels of bilirubin.

From the hematopoietic system: aplasticheskaya anemia, pancytopenia, neutropenia and agranulocytosis.

From the blood coagulation system: increased prothrombin time and international normalized ratio (MHO), hemolytic anemia and internal bleeding, positive direct Coombs test.

From the urinary system: renal dysfunction, toksicheskaya nephropathy, glycosuria, ketonwrïya.

Other: superimposed infection.

Contraindications

- Children up to age 6 Months;

- Hypersensitivity to the drug and other cephalosporins.

Tsedeks should be used with caution patients with complicated gastro-intestinal diseases, especially chronic colitis (history), and exclusively
gently patients with known or suspected allergy to penicillin.

Pregnancy and lactation

Adequate and well-controlled studies safety and efficacy of the drug during pregnancy and during childbirth were not carried out.

The results of studies of the effect of drugs on the reproductive function in animals are not always predictive of effects in humans, so the decision on the appointment of Tsedeksa during pregnancy should be evaluated estimated benefit to the mother and the potential risk to the fetus.

Ceftibuten not detected in breast milk.

Cautions

Approximately 5% Patients with an allergy to penicillin cross-reactivity is observed to cephalosporins. Patients, receiving both penicillins and cephalosporins, account Severe acute hypersensitivity reactions (anaphylaxis); there are cases of cross-hyperreactivity with the development of anaphylaxis. In the event of severe anaphylactic reactions shows emergency treatment (eg, adrenaline, in / in a liquid, airway, introduction of oxygen, antihistamines, corticosteroids, pryessornyye murder, active surveillance).

In the treatment of a broad spectrum antibiotic ( incl. Cedeksom) violation of intestinal microflora may lead to diarrhea, including pseudomembranous colitis, associated with the development of the toxin Clostridium difficile. Severity of diarrhea, accompanied or not by dehydration, can vary from mild to severe or life-threatening. Diarrhea can occur during or after antibiotic treatment. This diagnosis should be discussed in all cases, when persistent diarrhea occurs while taking any broad-spectrum antibiotic type Tsedeksa.

Cephalosporins, including Tsedeks, in rare cases, can reduce Prothrombin activity, which leads to an increase in the prothrombin time, especially in patients, previously stabilized on oral anticoagulation therapy. Patients, at risk, prothrombin time should be monitored and MHO. If necessary, it is recommended intake of vitamin K.

Influences Tsedeksa results of chemical or laboratory tests revealed no. The use of other cephalosporins sometimes recorded false positive direct Coombs test. However, the results of studies using red blood cells of healthy people have not confirmed the ability Tsedeksa cause positive Coombs test in vitro even at concentrations up to 40 ug / ml.

Overdose

In case of accidental overdose Tsedeksa signs of toxicity were observed. In healthy adult volunteers, Tsedeks received a single dose up 2 g, serious adverse reactions were, and all clinical and laboratory parameters remained within normal range.

Treatment: ceftibuten specific antidote does not exist, so you can spend an overdose gastric lavage. A considerable part of the dose Tsedeksa can be removed from the blood by hemodialysis. Efficiency of Peritoneal dialysis is not installed.

Drug Interactions

In special studies examined the interaction with the following medications Tsedeksa: antacids, hydroxides containing aluminum and magnesium at high doses, ranitidine and theophylline (single in / introduction). No evidence of clinically significant interactions have been identified. Tsedeksa Effect on plasma levels of theophylline or pharmacokinetics when administered Unknown. Information about the interaction with other drugs has not yet been received.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at a temperature of 2 ° to 25 ° C. The resulting suspension may be stored for 14 days in a refrigerator (at a temperature of from 2 ° to 8 ° C.). Shelf life – 2 year.