Tzedek - instructions for use, dose, side effects, contraindications

Active substanceCeftibutenCeftibuten

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Cedex®

capsules inwards

MSD FARMASYUTIKALS, LLC Russia

Cedex®

powdersuspension inwards

MSD FARMASYUTIKALS, LLC Russia

Dosage form: & nbspCapsules.

Composition:

1 capsule contains:

active substance: ceftibuten (in the form of ceftibutene dihydrate) -400 mg;

Excipients: microcrystalline cellulose - 60.0 mg, sodium carboxymethyl starch - 134.0 mg, magnesium stearate 6.0 mg;

shell capsules: sodium lauryl sulfate-0.06 mg, titanium dioxide-3.30 mg, gelatin-97.0 mg. The composition of the substance that adheres the capsule body and capsule includes: polysorbate-80-0.16 mg, gelatin-3.84 mg, purified water-q.s. The inscription "400 mg" on the shell of the capsule is printed with black pharmaceutical ink, which includes: shellac (pharmaceutical glaze), iron oxide black (E172), ethoxyethanol, SDA alcohol, lecithin, simethicone, purified water.

Description:

White color opaque hard gelatin capsules No. 0, which have on the body of the inscription black pharmaceutical ink "400 mg". Content - powder from white to light yellowish brown color.

Pharmacotherapeutic group:Antibiotic-cephalosporin.

ATX: & nbsp

J.01.D.D.14 Ceftibuten

Pharmacodynamics:

Ceftibuten, like most other beta-lactam antibiotics, has a bactericidal effect, suppressing the synthesis of the bacterial cell wall.The drug acts on many microorganisms that produce beta-lactamases and are resistant to penicillins and other cephalosporins.

Microbiology. Ceftibuten highly resistant to plasmid penicillinases and cephalosporinases. However, it is destroyed by the action of certain chromosomal cephalosporinases, which are produced by such microorganisms as Citrobacter spp., Enterobacter spp., Bacteroides spp., Morganella spp. and Serralia spp. Like other beta-lactams, ceftibutene should not be used for infections caused by bacterial strains whose resistance to beta-lactams is due to common mechanisms, such as changes in membrane permeability or modification of penicillin-binding proteins (PSB) (eg, penicillin-resistant Streptococcus pneumoniae). Ceftibuten interacts mainly with PSB-3 Escherichia coli, which leads to the formation of filamentous forms at a concentration of 1 / 4-1 / 2 of the minimum inhibitory concentration (MIC) and lysis at a concentration twice that of the MIC. The minimum bactericidal concentration (MBC) of ceftibutene for strains Escherichia coli, sensitive and resistant to ampicillin, approximately equal to the MIC.

Ceftibuten is active in vitro and in clinical practice with respect to most strains of the following microorganisms:

- Gram-positive microorganisms: Streptococcus pyogenes, Streptococcus pneumoniae (with the exception of penicillin-resistant strains);

- Gram-negative microorganisms: Haemophilus influenzae and Moraxella catarrhalis (Branhamella), including strains producing beta-lactamase, Escherichia coli, Klebsiella spp., Serratia spp., Morganella morganii.

Ceftibuten is inactive with respect to Enterococcus spp., Staphylococcus spp., Acinetobacter spp., Listeria spp., Flavobacterium spp. and Pseudomonas spp., Hafnia spp. Has a weak activity against anaerobes, including most species Bacteroides spp., Campylobacter spp., Yersinia spp. Destroyed by cephalosporinases of chromosomal origin Citrobacter spp., Enterobacter spp., Bacteroides spp.

Pharmacokinetics:Ingestion ceftibutene almost completely absorbed (90%) and output mostly unchanged kidneys. After a single dose of 400 mg capsules, the time to reach the maximum plasma concentration is 2-3 hours. The maximum plasma concentration is 15-17 μg / ml. The degree of binding of ceftibutene to plasma proteins is low (62-64%). The main ceftibutene derivative circulating in the plasma (ceftibuten-trans) appears to be formed by direct conversion of ceftibutene (cis-form). Ceftibuten-trans does not possess microbiological activity in vitro and in vivo in relation to staphylococci, enterococci, Acinetobacter spp., Bordetella, Listeria spp., Flavobacterium spp. and Pseudomonas spp., Campylobacter spp. and Yersinia spp., Hafnia spp. The concentration of ceftibutene-trans in plasma or urine is usually about 10% or less of the concentration of ceftibutene.

Bioavailability of ceftibutene depends on the dose in the therapeutic dose range (<400 mg) and varies from 75% to 94%.

Equilibrium concentrations of ceftibutene (if administered every 12 hours) in plasma are achieved after taking the fifth dose.

The half-life of ceftibutene from the plasma is 2 to 4 hours (2.5 hours on average) and does not depend on the dose or schedule of application.

Simultaneous food intake does not affect the effectiveness of the drug Tsedek^®in capsules.

Ceftibuten easily penetrates into body fluids and tissues. In the fluid of the skin bladder, which was experimentally induced in healthy volunteers receiving ceftibutene in a daily dose of 400 mg, the concentration of ceftibutene was comparable to that in plasma or exceeded it (compared to the areas under the curves "concentration-time" (AUC)). Ceftibuten is determined in the middle ear fluid in children with acute otitis media, where its concentration is approximately equal to or greater than its concentration in the plasma. Concentrations of ceftibutene in lung tissue are approximately 40% of plasma concentrations.The nasal, tracheal, bronchial secretions, bronchial-alveolar lavage fluid and its cell suspension ceftibuten concentration is approximately 46, 20, 24, 6 and 81% of the plasma concentrations respectively.

Ceftibuten is found in the urine within 24 hours after taking 400 mg; the maximum concentration in urine is 264 μg / ml and is reached within the first 4 hours; after 20-24 hours after a single administration of ceftibutene, its concentration in the urine is 10.5 μg / ml.

Data of ceftibuten concentration in the cerebrospinal fluid have, however, the application of oral cephalosporins their content in cerebrospinal fluid normally reaches a therapeutic level.

In elderly people, equilibrium concentrations of ceftibutene (when administered every 12 hours) are achieved after taking the fifth dose. The mean AUC in this group is slightly higher than in younger patients. With repeated use of ceftibutene in elderly people, cumulation was negligible.

Indications:

Treatment of infections caused by microorganisms sensitive to ceftibutene:

- infections of the upper respiratory tract, including pharyngitis, tonsillitis and acute sinusitis in adults;

acute otitis media in children;

- Lower respiratory infections in adults, including exacerbation of chronic bronchitis;

- urinary tract infections: acute and chronic pyelitis, cystopyelitis, cystitis,

urethritis.

Contraindications:

- Hypersensitivity to ceftibutene, cephalosporins or any component of the drug.

- Children under 12 years old and weighing up to 45 kg due to the inability to properly dispense capsules of CEDEX ® in young children.

Carefully:

Assign the drug to patients:

- with known or suspected allergies to penicillins;

- with complicated gastrointestinal diseases, especially chronic colitis, in the anamnesis;

- with an average degree and severe renal insufficiency (creatinine clearance less than 50 ml / min) and patients on hemodialysis.

- with allergic reactions, including in the anamnesis (except for those indicated in the section "Contraindications"),

Pregnancy and lactation:

Controlled studies of drug use in pregnant women have not been conducted. Studies on animals have not revealed its damaging effect on the course of pregnancy or childbirth,to embryonic or postnatal development. However, when prescribing Cedex®, pregnant women should compare the benefits to the mother and the risk to the fetus. Cedex® is not recognized in breast milk in nursing women, but use of the drug in women during lactation should be taken with caution.

During the period of breastfeeding, Cedex® is used only if the intended benefit to the mother exceeds the potential risk to the child.

Dosing and Administration:

For oral administration. The drug Cedex® in capsules can be taken regardless of food. The duration of treatment with Cedex® is usually 5 to 10 days. In the treatment of infections caused by Streptococcus pyogenes, Cedex® in a therapeutic dose should be used for at least 10 days.

Adults. The recommended dose of Cedex® is 400 mg / day. In the treatment of acute bacterial sinusitis, exacerbation of chronic bronchitis and urinary tract infections (acute and chronic pyelitis, cystopyelitis, cystitis, urethritis), the drug can be used 400 mg once a day. The duration of therapy is 5-10 days, depending on the severity and type of the disease.

Adult patients with impaired renal function. With mild renal insufficiency, the pharmacokinetics of the Cedex® preparation does not change significantly, so a dose change is required only when the creatinine clearance is less than 50 ml / min. Cedex® 400 mg can be used every 48 hours (once every 2 days) with a creatinine clearance of 30-49 ml / min or every 96 hours (1 every 4 days) with a creatinine clearance of 5-29 ml / min. Patients receiving hemodialysis treatment two or three times a week, Cedex® can be administered 400 mg at the end of each hemodialysis session.

Children. Cedex® capsule can be used in children from the age of 12 and weighing 45 kg or more in a dose recommended for adults.

In the treatment of pharyngitis, accompanied or not accompanied by tonsillitis, acute otitis media and urinary tract infections (acute and chronic pyelitis, cystopyelitis, cystitis, urethritis), the drug can be applied once a day.

Side effects:

The most common side effects are nausea, diarrhea and headache.

Infrequent: dyspepsia, gastritis, vomiting, abdominal pain, dizziness and symptoms similar to those with serum sickness, taste change, nasal congestion, rash, drowsiness.

Rare: growth Clostridium difficile, combined with moderate or severe diarrhea; changes on the part of laboratory indicators - reduction of hemoglobin, leukopenia, eosinophilia, thrombocytosis, transient increase in activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT)

and lactate dehydrogenase (LDH) in serum. Very rare: convulsions.

With the use of Cedex®, the following side effects are possible: Candidiasis, vaginitis, superinfection, prolongation of prothrombin time, an increase in the international normalized ratio (MHO), thrombocythemia, aplastic anemia, hemolytic anemia, blood clotting disorder, pancytopenia, neutropenia, agranulocytosis, hypersensitivity reactions, including anaphylactic reactions, bronchospasm, rash, urticaria, photosensitivity, itching, angioedema, toxic erythema multiforme, paresthesia, aphasia, psychotic disorders, anorexia , shortness of breath, constipation, dryness of the oral mucosa, flatulence, fecal incontinence, melena; jaundice, dysuria, impaired renal function, toxic nephropathy, glucosuria and ketonuria, fatigue.

Side effects of all cephalosporins

Infections and infestations: superinfection; disorders of the immune system: allergic reactions, including anaphylaxis, bronchospasm, dyspnea, rash, hives, reactions of increased photosensitivity, pruritus, angioedema, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis;

gastrointestinal disorders: severe diarrhea and colitis associated with antibiotic treatment, including pseudomembranous colitis; and

Changing laboratory indicators: rarely - an increase in prothrombin time and (MHO). Renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia and internal bleeding, hyperbilirubinemia, positive reaction Coombs, glucosuria, ketonuria, pancytopenia, neutropenia, agranulocytosis, drug fever, cholestasis.

Side effects in children: diarrhea, vomiting, abdominal pain, loose stools, agitation, anorexia, dehydration, diaper dermatitis, dizziness, dyspepsia, fever, headache, hematuria, hyperkinesia, agitation, insomnia, irritability, nausea, pruritus, rash, urticaria.

Also in post-marketing practice, the following adverse reactions were observed: Stevens-Johnson syndrome and toxic epidermal necrolysis (Laill's syndrome).

Overdose:

In case of an accidental overdose of Cedex®, no signs of toxicity were noted. The antidote of ceftibutene does not exist, therefore, when overdosing, it is possible to wash the stomach. A significant portion of the dose of Cedex® can be removed from the blood by hemodialysis. The effectiveness of peritoneal dialysis is not established.

In healthy adult volunteers who received the Cedex® single dose at a dose of up to 2 g, there were no serious adverse reactions, and all clinical and laboratory parameters remained within normal limits.

Interaction:

Special studies have investigated the interaction of ceftibutene with the following drugs: antacids containing aluminum and magnesium hydroxide in high doses, ranitidine and theophylline (single intravenous administration). Signs of significant interaction are not revealed. The effect of ceftibutene on plasma concentration or the pharmacokinetics of theophylline upon ingestion is not known.Information about the interaction with other means has not been received to date. Cephalosporins, including ceftibutene, in rare cases can reduce prothrombin activity, which leads to an increase in prothrombin time, especially in patients previously stabilized by oral anticoagulant therapy. Patients at risk should be monitored for prothrombin time and MHO. If necessary, the introduction of vitamin K is recommended.

Impact on laboratory results

Effects of ceftibutene on the results of chemical or laboratory indicators were not revealed. When using other cephalosporins, a false positive direct Coombs test was sometimes recorded. However, the results of studies using erythrocytes in healthy humans did not confirm the ability of ceftibutene to induce a positive Coombs test in vitro, even at concentrations up to 40 μg / ml.

Special instructions:

Long-term treatment with broad-spectrum antibiotics can lead to the development of resistance of microorganisms to the drug. When developing seizures or an anaphylactic reaction, it is necessary to cancel the drug and begin the appropriate treatment.

It is recommended to exercise extreme caution when using Cedex® with patients with allergic reactions of any kind (eg, hay fever and bronchial asthma), because they are not tolerated. these patients are at increased risk of severe hypersensitivity reactions.

Approximately 10% of patients with penicillin allergy have a cross-reaction to cephalosporins. In patients who received both penicillins and cephalosporins, hypersensitivity reactions (anaphylaxis) were recorded; There are cases of cross-reactivity with the development of anaphylaxis. In case of serious anaphylactic reactions, urgent therapy is indicated (for example, epinephrine, glucocorticosteroids, intravenous fluids, airway patency, oxygen administration, antihistamines, and dynamic observation).

In the treatment of broad-spectrum antibiotics such as Cedex, "disruption of the intestinal microflora can lead to diarrhea, including pseudomembranous colitis associated with the production of Clostridium difficile toxin." In light cases, it is sufficient to discontinue treatment and use ion-exchange resinscolestramine, colestipol), in severe cases, compensation for loss of fluid, electrolytes and protein, the appointment of vancomycin, bacitracin or metronidazole. Do not use drugs that violate intestinal motility.

The severity of diarrhea, accompanied or not accompanied by dehydration, can range from moderate to severe or life threatening. Diarrhea may occur during or after treatment with an antibiotic. This diagnosis should be discussed in all cases when persistent diarrhea appears against the background of taking any broad-spectrum antibiotic, such as Cedex®.

Effect on the ability to drive transp. cf. and fur:Data suggesting that the administration of Cedex® capsule 400 mg affects the ability to drive a car or moving machinery has not been identified. Patients should be warned about the possibility of developing dizziness, seizures, in the appearance of which it is necessary to refuse to perform these activities.

Form release / dosage:Capsules 400 mg.

Packaging:1 capsule in a bag of aluminum foil, laminated with polyethylene. For 5 bags together with instructions for use in a cardboard pack.

Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013725 / 01

Date of registration:23.01.2009

The owner of the registration certificate:MSD FARMASYUTIKALS, LLC MSD FARMASYUTIKALS, LLC Russia

Manufacturer: & nbsp

MERCK SHARP & DOHME, Corp. USA

Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.

Information update date: & nbsp10.11.2015

Illustrated instructions

Instructions

Cedex® (Cedax®)