2010/06/16

Cedax

Composition, structure and packing

Capsules are white or yellowish-white; content capsules - powder white or yellowish. 1 capsule. tseftibuten 400 mg. Excipients: microcrystalline cellulose, sodium starch glycolate, magnesium stearate. The composition of the capsule shell: titanium dioxide.

Powder for Oral suspension from light yellow to dark yellow, the water forms a light-yellow suspension with a characteristic cherry scent. 1 ml final suspensions. tseftibuten (in the form of dihydrate) 36 mg. Excipients: Xanthan gum, sucrose, Simethicone, silicon dioxide, polysorbate 80, sodium benzoate, food additives with cherry taste.

Clinico-pharmacological group: cephalosporins III generation.

Pharmacological action

Cephalosporins III generation. Is beta-lactam antibiotic has a bactericidal effect, the mechanism of which is due to suppression of synthesis of the bacterial cell wall. Features of the chemical structure tseftibutena determine its high resistance to β-lactamases, which accounts for activity against many microorganisms producing β-lactamases and resistant to penicillin and other cephalosporins. Tseftibuten vysokoustoychiv to penicillinase plasmid and tsefalosporinazam, but is sensitive to the action of certain chromosomal tsefalosporinaz which are produced Citrobacter spp., Enterobacter spp. and Bacteroides spp. The drug should not be used for infections caused by strains of bacteria, whose stability to beta-lactam antibiotics due to common mechanisms, such as changes of permeability or penicillin-binding proteins (PRP) (eg, penitsillinorezistentny Streptococcus pneumoniae). Tseftibuten interacts mainly with the PRP-3 Escherichia coli, which leads to the formation of filar forms at a concentration equal to 1/4-1/2 the IPC, and lysis at a concentration twice the IPC. The minimum bactericidal concentration tseftibutena for strains Escherichia coli, sensitive and resistant to ampicillin, approximately equal to the IPC. Active in vitro and in clinical practice for most strains of the following Gram-positive microorganisms: Streptococcus pyogenes, Streptococcus pneumoniae (excluding penitsillinorezistentnyh strains), Gram-negative microorganisms: Haemophilus influenzae (strains producing and not producing β-lactamases), Haemophilus parainfluenzae (strains producing and do not produce β-lactamase), Moraxella (Branhamella) catarrhalis (most strains produce β-lactamase), Escherichia coli, Klebsiella spp. (Including Klebsiella pneumoniae and oxytoca), indole-positive Proteus spp. (Including Proteus vulgaris), and Providencia spp., Proteus mirabilis, Enterobacter spp. (Including Enterobacter cloacae and Enterobacter aerogenes), Salmonella spp., Shigella spp. Active in vitro against most strains of these organisms, but its clinical efficacy has not been established; gram-positive organisms: Streptococcus spp. Groups C and G; Gram-negative microorganisms: Brucella spp., Neisserria spp., Aeromonas hydrophilia, Yersinia enterocolitica, Providencia rettgeri, Providencia stuartii strains and Citrobacter spp., Morganella spp. and Serratia spp., which do not produce large quantities of chromosomal tsefalosporinazy. Inactive against Staphylococcus spp., Enterococcus spp., Acinetobacter spp., Listeria spp., Flavobacterium spp. and Pseudomonas spp., weakly active against most anaerobes, including most strains of Bacteroides. Tseftibuten-trans does not have microbiological activity in vitro and in vivo against the same strains.

Pharmacokinetics

Absorption

After taking the drug inside tseftibuten almost completely absorbed from the gastrointestinal tract (90%). Cmax was reached after 3 h after a single oral capsules 400 mg. Bioavailability tseftibutena depends on the dose in the therapeutic dose range (≤ 400 mg). The speed and extent of absorption tseftibutena when receiving Tsedeksa in the form of suspension changes, while taking a high-calorie fatty foods.

Distribution

Cvyazyvanie tseftibutena to plasma proteins is low (62-64%). There are no adequate data on the concentration in the cerebrospinal fluid tseftibutena not, but when taking other cephalosporins into their content in the cerebrospinal fluid usually does not reach therapeutic levels. After receiving a single oral dose of tseftibutena 200 mg it was not detected in breast milk in lactating women. In young adult volunteers Css tseftibutena (when given every 12 h) in plasma were achieved after receiving the fifth dose. A notable cumulation of the drug with repeated use is not marked. Studies have shown that tseftibuten easily penetrates into a liquid medium and tissues. In a liquid skin bubble concentration tseftibutena was comparable to that in plasma or exceeded it (on the basis of comparison AUC). Tseftibuten penetrated into the middle ear fluid in children with acute otitis media, where its concentration was approximately equal levels in plasma or exceed it. Concentrations tseftibutena in lung tissue were approximately 40% of the concentrations in plasma. In nasal, tracheal and bronchial secretion, broncho-alveolar lavage fluid and cell suspension concentration tseftibutena were respectively about 46, 20, 24, 6 and 81% of the concentrations in plasma.

Metabolism and excretion

The main derivative tseftibutena circulating in plasma (tseftibuten-trans), apparently formed by direct conversion tseftibutena (cis-form). Concentration tseftibutena-trans in plasma or urine is usually around 10% or less of the concentration tseftibutena. T1 / 2 tseftibutena from the plasma of 2 to 4 hours (average 2.5 hours) and does not depend on the dose or use schemes. Write mainly unchanged in the urine. Tseftibuten detected in the urine within 24 h after administration of 400 mg; Cmax in urine was 264 ug / ml and was achieved during the first 4 h after 20-24 h after a single dose of the drug concentration in urine tseftibutena was 10.5 micrograms / ml.

Pharmacokinetics in special clinical situations

In elderly volunteers Css tseftibutena (when given every 12 h) were achieved after receiving the fifth dose. The average AUC in this group was slightly higher than in young adults. With repeated use tseftibutena in elderly accumulation was negligible. Pharmacokinetics tseftibutena not significantly changed with chronic active hepatitis, cirrhosis, alcoholic disease and other liver diseases, accompanied by necrosis of hepatocytes. AUC and T1 / 2 tseftibutena from plasma increased as renal failure.

In patients with creatinine clearance <5 ml / min, AUC and T1 / 2 were 7-8 times higher than in healthy individuals. A single hemodialysis leads to the elimination of approximately 65% of the dose tseftibutena from the plasma.

Statement

Treatment of infectious-inflammatory diseases caused by susceptible microorganisms:
infections of the upper respiratory tract (including pharyngitis, tonsillitis and scarlet fever in adults and children, acute sinusitis in adults, otitis media in children);
Infection of lower respiratory tract in adults (including acute bronchitis, exacerbation of chronic bronchitis and severe pneumonia) in those cases where the possible admission of drug inside, ie with community-acquired infections;
urinary tract infections in adults and children (including complicated and uncomplicated);
enteritis and gastroenteritis in children caused Salmonella spp., Shigella spp. and Escherichia coli (tseftibuten not active against Campylobacter spp. and Yersinia spp.).

Dosage regimen

Duration of therapy (as well as the use of other antibiotics for oral administration) is from 5 to 10 days.
In the treatment of infections caused by Streptococcus pyogenes, Tsedeks in a therapeutic dose should be applied for at least 10 days. For adults the recommended dose Tsedeksa is 400 mg / day. Tsedeks capsules can be taken irrespective of food.
In acute bacterial sinusitis, acute bronchitis, aggravation of chronic bronchitis and complicated and uncomplicated urinary tract infection drug may be used in a dose of 400 mg 1 time / day.
In community-acquired pneumonia and the possibility of taking the drug inside the recommended dose Tsedeksa is 200 mg every 12 hours

Adult patients in violation of renal function change in dose is required only for reducing the spacecraft is less than 50 ml / min. When spacecraft from 49 to 30 ml / min daily dose should be reduced to 200 mg or designate by 400 mg every 48 hours (a day), with the spacecraft from 29 to 5 ml / min recommended daily dose is 100 mg or a drug prescribed for 400 mg every 96 hours (3 days). In patients receiving hemodialysis for 2 or 3 times a week, Tsedeks can be assigned to 400 mg at the end of each hemodialysis.

Children of drug is preferable to designate in the form of suspension, the recommended dose of 9 mg / kg / day. The maximum dose - 400 mg / day. Pharyngitis (including those with tonsillitis), acute purulent otitis media and urinary tract infections (including complications), the medication can be used 1 time per day. In acute bacterial enteritis in children daily dose can be divided into 2 divided doses (based on 4.5 mg / kg every 12 hours).

For children weighing over 45 kg or over the age of 10 years, the drug can be given at the recommended adult dose. Safety and efficacy Tsedeksa in children under 6 months are not installed. The suspension Tsedeksa can take approximately 1-2 hours before or after a meal. Before taking the drug vial must shake vigorously.

Side effect

Adverse events were recorded in patients who received Tsedeks:
On the part of the digestive system: nausea (≤ 3%), diarrhea (3%), rarely - indigestion, gastritis, vomiting, abdominal pain, increased activity of AST, ALT and LDH, very rarely - the growth of Clostridium difficile, combined with moderate or marked diarrhea.
From the side of the central nervous system: headache, rarely - dizziness, rarely recorded seizures, which were not definitely related to treatment (convulsions were observed 5 days after starting treatment Tsedeksom one elderly patient with chronic obstructive lung disease who had received various drugs, including theophylline ).
On the part of the hemopoietic system: reduction of hemoglobin, leukopenia, eosinophilia, thrombocytosis. Adverse events were recorded in patients in the treatment of various cephalosporins Allergic reactions: anaphylaxis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis.
On the part of the digestive system: marked diarrhea, colitis, increased levels of bilirubin.
On the part of the hemopoietic system: aplastic anemia, hemolytic anemia, bleeding, positive direct Coombs test, pancytopenia, neutropenia and agranulocytosis.
From the urinary system: kidney, toxic nephropathy, Glycosuria, ketonuria. Other: superinfection.

In clinical studies in approximately 3000 patients demonstrated the safety and tolerability of good Tsedeksa. Most adverse events were mild and transient marked and rare or very rare. Most adverse reactions yielded symptomatic therapy or were after the abolition Tsedeksa.

Contraindications
Hypersensitivity to any component drug and to other cephalosporins.

Pregnancy and lactation

Adequate and strictly controlled studies safety and efficacy of the drug during pregnancy and childbirth were not conducted. The results of studies of the effect of drugs on reproductive function in animals is not always possible to predict their effects in humans, so if the decision to appoint Tsedeksa during pregnancy should assess the intended benefits to the mother and the potential risk to the fetus. Tseftibuten not excreted in breast milk.

Application for violations of renal function

Adult patients in violation of renal function change in dose is required only for reducing the spacecraft is less than 50 ml / min. When spacecraft from 49 to 30 ml / min daily dose should be reduced to 200 mg or designate by 400 mg every 48 hours (a day), with the spacecraft from 29 to 5 ml / min recommended daily dose is 100 mg or a drug prescribed for 400 mg every 96 hours (3 days).

Patients receiving hemodialysis 2 or 3 times a week, Tsedeks can be assigned to 400 mg at the end of each hemodialysis.

Cautions

Precautions should be appointed Tsedeks patients with complicated gastrointestinal diseases in history (especially in chronic colitis). Extremely cautiously prescribe cephalosporin to patients with known or suspected allergic to penicillin. Approximately 5% of patients with allergy to penicillin observed cross-reactivity to cephalosporins.

In patients treated with both penicillins and cephalosporins, are registered serious acute hypersensitivity reactions (anaphylaxis) have been known to cross with the development of hyperreactivity anaphylaxis.
In the event of serious anaphylactic reactions shown emergency treatment (eg, epinephrine, in / in the introduction of fluid, providing airway, the introduction of oxygen, antihistamines, corticosteroids, pressor amines, active surveillance).
In the treatment of broad spectrum antibiotics (including Tsedeksom) violation of the intestinal microflora can cause diarrhea, including pseudomembranous colitis associated with the elaboration of toxin Clostridium difficile.

Severity of diarrhea, accompanied or not by dehydration, can vary from mild to severe or life-threatening. Diarrhea may occur during or after antibiotic treatment. This diagnosis should be discussed in all the cases where persistent diarrhea appears on a background of reception of any broad-spectrum antibiotic such as Tsedeksa. Influences Tsedeksa the results of chemical or laboratory tests were found.
When using 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 mg / ml.

Overdose

In case of accidental overdose Tsedeksa signs of toxicity were not observed. In healthy adult volunteers who received Tsedeks once at a dose of 2 g, serious adverse reactions were not, and all clinical and laboratory parameters were within normal limits. Treatment: specific antidote tseftibutena not exist, so an overdose can be gastric lavage. Much of the dose Tsedeksa can be removed from the blood by hemodialysis. The effectiveness of peritoneal dialysis is not installed.

Drug Interactions

In special studies investigated the interaction Tsedeksa with the following medications: antacids with aluminum hydroxide and magnesium in high doses, ranitidine, and theophylline (single in / in the introduction). No evidence of clinically significant interactions were found.

Influence Tsedeksa on plasma levels or pharmacokinetics of theophylline ingestion is not known. Information about the interaction with other drugs have so far been received.

Terms and Conditions of storage

The drug should be stored at 2 ° to 25 ° C. Prepared suspension can be stored for 14 days in the refrigerator (2 ° to 8 ° C). Shelf life of the drug in capsule form - 2 years, in the form of powder for suspension - 2.5 years.

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