Spectrate (Spektracef)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceCefeditorinCefeditorin
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  • Spectrate
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    Meiji Seika Pharma Co., Ltd.     Japan
    • Dosage form: & nbspFilm-coated tablets.
    Composition:Dosage of 200 mg: mannitol as needed (approximately 35 mg), sodium caseinate 100 mg, croscarmellose sodium 150 mg, sodium tripolyphosphate 4 mg, magnesium stearate 5 mg, Opadrai white 35 mg (hypromellose 21.9 mg, titanium dioxide 10.9 mg, macrogol-400 2.2 mg), carnauba wax 0.06 mg, Opacod blue ink (shellac IN IMS 74 OP 50.41%, N-butanol 24.35%, Aluminum dye based on diamond blue CFF 11.25%, titanium dioxide 4.49%, propylene glycol 2.91%, isopropanol 4.65%, ammonia solution concentrated 1.94%).

    Dosage of 400 mg: mannitol as needed (approximately 70 mg), sodium caseinate 200 mg, croscarmellose sodium 300 mg, sodium tripolyphosphate 8 mg, magnesium stearate 10 mg, Opadrai white 55 mg (hypromellose 34.4 mg, titanium dioxide 17.2 mg, macrogol-400 3,4 mg), carnauba wax 0,01mg, opakod blue ink (shellac IN IMS 74 OP 50.41%, N-butanol 24.35%, Aluminum dye based on diamond blue CFF 11.25%, titanium dioxide 4 , 49%, propylene glycol 2.91%, isopropanol 4.65%, ammonia solution concentrated 1.94%).
    Description:White elliptical tablets covered with a film sheath, marked "TMF" in blue on one side. On the cross section, the core is light yellow in color.
    Pharmacotherapeutic group:Antibiotic-cephalosporin.
    ATX: & nbsp

    J.01.D.D.16   Cefeditorin

    Pharmacodynamics:

    Mechanism of action

    Cefeditorena pivsil - semisynthetic beta-lactam antibiotic, is a prodrug of cefditoren (third generation cephalosporin). The mechanism of action of the drug is associated with the inhibition of bacterial wall synthesis due to its affinity for penicillin-binding proteins.

    Pharmacokinetic / pharmacodynamic features

    When the drug is administered at a dose of 200 mg twice a day, its plasma concentration exceeds the minimum inhibitory concentration in relation to 90% of microorganisms (MIC90) for Moraxella catarrhalis, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pyogenes and penicillin-sensitive strains Streptococcus pneumoniae for at least 50% of the time from the dosing interval. The administration of cefeditorin 400 mg twice daily provides maintenance of its concentration above the minimum inhibitory concentration (MIC) for 51% of the time from the dosing interval, which exceeds the minimum inhibitory concentration in relation to 50% of microorganisms (MIC50) for Streptococcus pneumoniae, resistant to penicillin.

    Mechanisms of resistance

    Cefditoren as a third generation cephalosporin has common resistance mechanisms for this group of antibiotics.The resistance of Gram-positive microorganisms can be associated with a change in the penicillin-binding protein Streptococcus pneumoniae and Streptococcus viridans, or the appearance of an additional penicillin-binding protein (PBP2a) in Staphylococcus spp. Cefditoren is resistant to most of the most common chromosomal and plasmid beta-lactamases of gram-negative bacteria. However, like other cephalosporins, cep is hydrolyzed by broad spectrum beta-lactamases mediated by plasmids. In addition, the cause of resistance is the development of chromosomal beta-lactamase in mutant strains Enterobacter spp., Citrobacter spp., Morganella spp. and Serratia spp. The mechanism of action of cefditoren is similar to other cephalosporin antibiotics and differs from the mechanism of action of other groups of antibiotics. In general, there was no evidence of cross-resistance between cefditoren and other groups of antibiotics. However, in rare cases, some mechanisms of action (for example, related to the impermeability of the internal membrane or the presence of a mechanism for active removal of the antibiotic from the cell) may be similar for all groups of antibiotics.This causes a certain level of resistance to all antibiotics.

    The minimum inhibitory concentration (MIC)

    Recommended values ​​of MIC for cefditoren, allowing to classify microorganisms with high, intermediate sensitivity and resistance: sensitive - < 0.5 μg / ml, with an intermediate sensitivity of> 0.5 μg / ml and <2 μg / ml, resistant - > 2 μg / ml.

    Sensitivity

    The table below provides information on the sensitivity spectrum of most microorganisms for approved indications for use.

    The prevalence of acquired resistance may vary depending on the geographical area, as well as in individual pathogens. For this reason, it is desirable to obtain information on the sensitivity of microorganisms in a particular region, especially when treating a serious infection. In cases where the resistance of pathogens is doubtful, you can seek help from a specialist who will assess the advisability of prescribing cefditorin in a specific clinical case.

    Usually sensitive species (resistance less than 10%, European data)

    Aerobic Gram-positive microorganisms:

    Streptococci groups C and G

    Methicillin-sensitive strains Staphylococcus aureus1

    Streptococcus agalactiae S

    treptococcus pneumoniae1, 2

    Streptococcus pyogenes1

    Aerobic gram-negative microorganisms:

    Haemophilus influenzae1

    Moraxella catarrhalis1

    Anaerobic microorganisms:

    Clostridium perfringes

    Peptostreptococcus spp.

    Microorganisms from the original resistance to cefeditoren

    Aerobic Gram-positive microorganisms: Enterococcus spp.

    Methicillin-resistant strains Staphylococcus aureus

    Aerobic Gram-negative microorganisms:

    Acinetobacter baumanii

    Pseudomonas aeruginosa

    Anaerobic microorganisms:

    Group Bacteroides fragilis

    Clostridium difficile

    Other: Chlamydia spp. Mycoplasma spp. Legionella spp.

    1 - Clinical efficacy was shown for susceptible pathogens according to approved indications.

    2 - Some strains with high resistance to penicillin may have a decreased sensitivity to cefeditoren. The strains resistant to cefotaxime and ceftriaxone should not be considered as sensitive to cefotoren.

    Gram-negative microorganisms that contain chromosomal beta- lactamases, such as Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Morganella morganii, Serratia marcescens, should be considered as resistant to cefthotorene, despite their apparent susceptibility in vitro.

    Pharmacokinetics:

    Suction

    After ingestion of cefeditorin pivocil, it is absorbed in the gastrointestinal tract and under the action of esterases hydrolyzed to cefditoren.Ingestion of 200 mg of the drug after a meal is accompanied by the attainment of a maximum concentration (CmOh), equal to 2.6 μg / ml, after about 2.5 hours, while taking 400 mg of the drug leads through the same period of time to the achievement of CmOh, equal to 4.1 μg / ml. Absolute bioavailability of cefeditorin after ingestion compared with intravenous administration is about 15-20%.

    The presence of food in the gastrointestinal tract speeds up the absorption of cefeditorin of the beer, which leads to an increase in the CmOh and the area under the pharmacokinetic curve "concentration-time" (AUC) on 50% and 70% in comparison with the values ​​on an empty stomach, respectively.

    Binding to plasma proteins and distribution

    The binding of cefditoren to plasma proteins is 88%.

    After repeated and single administration of the drug, the pharmacokinetic parameters did not differ; this indicates the absence of cumulation. The volume of distribution of cefditorin under conditions of equilibrium concentration does not differ significantly from this index, calculated after a single injection; it is practically independent of the administered dose and always remains within 40-65 liters.

    After a single injection of 400 mg of the drug, the penetration into the mucosa and the secretion of the bronchi was 60% and 20% of the concentration in the blood plasma, respectively. The results of administration of a similar dose to healthy volunteers and subsequent evaluation of the penetration of the antibiotic into the interstitial fluid showed that after 8 and 12 hours, the concentration of cefditoren in the interstitial fluid reached 40% and 56% of the plasma area area under the pharmacokinetic curve, respectively.

    Metabolism / excretion

    Regardless of the dose and duration of treatment, up to 18% of the administered dose of cefditoren is excreted unchanged by the kidneys.

    The half-life of the drug from the plasma is about 1.0-1.5 hours. The total clearance with a correction for bioavailability is about 25-30 l / h, renal clearance is about 80-90 ml / min. Studies of labeled cefditorin in healthy volunteers showed that the non-sucked part of the drug is excreted through the intestine, and a large proportion of cefditoren is converted to inactive metabolites - P7 and M-OH. In the process of hydrolysis of ceftedorene, a pivalate is formed, which is excreted by the kidneys in the form of pivaloylcarnitine conjugate.

    Special patient groups

    Floor

    The pharmacokinetics of ceftedorene pivoxil does not differ significantly in a person depending on sex.

    Elderly patients

    In appointing the same doses, the concentration of cefditorin in elderly patients (over the age of 65) is slightly higher than in the adult population middle-aged; indicators C mOh and AUC in such patients, about 26% and 33%, respectively, are higher. Except for cases of severe renal and / or hepatic failure, elderly patients do not need a dose adjustment.

    Impaired renal function

    After repeated administration of cefeditorin, 400 mg of pioxylate AUC in healthy volunteers and patients with renal damage of varying severity are as follows.

    Kidney function

    Creatinine clearance

    AUC0-12 (mean ± SD1) (ng.h / ml)

    Normal

    > 80 ml / min

    11349,3 (1900,8)

    Renal insufficiency:

    Lightweight

    51-80 ml / min

    12856,1 (4522,4)

    Moderate

    30-50 ml / min

    31083,6 (9401,6)

    Heavy

    <30 ml / min

    34279,8 (13472,4)

    1 - CO is the standard deviation.

    The noted changes in the pharmacokinetic parameters of cefditoren in patients with impaired renal function of mild degree are not considered clinically significant.In patients with moderate and severe renal failure, the indicator AUC approximately 3 times higher compared to healthy volunteers. Currently available data do not allow you to recommend any doses of the drug to patients on hemodialysis.

    Impaired liver function

    The effect of liver function disorders of mild or moderate severity on the pharmacokinetics of cefeditorin pivoxil after its administration at a dose of 400 mg includes a slight increase in the main pharmacokinetic parameters without statistically significant differences. In addition, there was a slight increase in the amount of the drug excreted by the kidneys, compared to healthy volunteers. Similar data in patients with severe hepatic insufficiency have not yet been obtained.

    Liver function

    AUC0-12 (mean ± SD) (ng.h / mL)

    Normal

    15733,2 (2935,7)

    Liver failure:

    Light (Class A Child-Pugh)

    17932,4 (4494,2)

    Moderate (Child-Pugh class B)

    17425,1 (5804,2)

    Indications:
    Treatment of infections caused by microorganisms sensitive to cefeditoren:

    - infections of the upper respiratory tract: acute tonsillopharyngitis, acute sinusitis;

    - infections of the lower respiratory tract: exacerbation of chronic bronchitis, community-acquired pneumonia;

    - uncomplicated infections of the skin and subcutaneous fat: phlegmon, infected skin wounds, abscess, folliculitis, impetigo and furunculosis.
    Contraindications:
    - Hypersensitivity to cefditoren, other cephalosporins or any other component of the drug;

    - severe allergic reactions to penicillins and other beta-lactam antibacterials;

    - hepatic insufficiency of class C in Child-Pugh;

    - patients on hemodialysis;

    - hypersensitivity reactions to protein casein in history;

    - primary carnitine insufficiency;

    - children's age till 12 years;

    - simultaneous use of ceftodirene pivoksila and blockers of H2-histamine receptors.
    Carefully:
    Patients with increased sensitivity to other beta-lactam antibiotics because of the possibility of developing cross-allergic reactions.
    Simultaneous use with aminoglycosides and diuretics (furosemide).
    Patients with pathology of the gastrointestinal tract, including colitis in the anamnesis.
    Pregnancy and lactation:
    Pregnancy
    Clinical data on the use of cefeditorene pivoksila in pregnant women are not obtained. And although studies in animals have not shown embryotoxic or teratogenic effects of the drug, Spectracef should not be used during pregnancy, except when the expected benefit to the mother exceeds the potential risk to the fetus.

    Lactation period
    Data on the penetration of cefditoren into breast milk is not enough. Therefore, when using Spectracef, breast-feeding should be discontinued.
    Dosing and Administration:

    Inside.

    Tablets should be swallowed whole, with plenty of water, preferably after eating.

    The recommended dose depends on the severity of the infection, the initial condition of the patient and the potential causative agents of the infection.

    Adults and children over 12 years of age

    - Acute pharyngthongsillitis, acute sinusitis and uncomplicated infections of the skin and subcutaneous fat: 200 mg every 12 hours for 10 days.

    - Exacerbation of chronic bronchitis: 200 mg every 12 hours for 5 days.

    - Community-acquired pneumonia: 200 mg every 12 hours for 14 days. In severe cases, recommend a dose of 400 mg every 12 hours for 14 days.

    Elderly patients

    For elderly patients, except for cases of severe impairment of liver and / or kidney function, dose adjustment is not required.

    Impaired renal function

    In patients with mild renal impairment, dose adjustment is not required. In patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min), the recommended dose should not exceed 200 mg twice a day. In patients with severe renal failure (creatinine clearance less than 30 ml / min), the maximum daily dose should not exceed 200 mg. In patients on hemodialysis, the recommended dose is not established.

    Impaired liver function

    In patients with mild or moderate impairment of liver function, dose adjustment is not required (Child-Pugh classes A or B). With severe hepatic insufficiency (Child-Pugh class C), data allowing to prescribe the recommended dose are not obtained.

    Side effects:

    The undesirable phenomena presented below are listed depending on the anatomical and physiological classification and frequency of occurrence. Frequency of occurrence is defined as follows: Often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1 000 and <1/100), rarely (> 1/10 000 and <1/1 000), rarely (<1/10 000, including individual cases).

    From the side of metabolism and nutrition

    Rarely: anorexia.

    From the nervous system

    Often: headache.

    Rarely: nervousness, dizziness, insomnia, drowsiness, sleep disorders.

    From the side of the organ of vision

    Very rarely: photosensitivity.

    From the side of AOP-organ

    Very rarely: pharyngitis, rhinitis, sinusitis, ringing in the ears.

    On the part of the respiratory system, the organs of the thorax and the mediastinum

    Very rarely: bronchospasm.

    From the gastrointestinal tract

    Very often: diarrhea.

    Often: nausea, abdominal pain, indigestion.

    Rarely: constipation, flatulence, vomiting, candidiasis of the oral cavity, belching, pseudomembranous colitis, dry mouth mucosa, perversion of taste.

    Very rarely: aphthous stomatitis.

    From the liver and biliary tract

    Rarely: a violation of the liver.

    From the skin and subcutaneous fat

    Rare, rash, itching, urticaria.

    From the side of the musculoskeletal system and connective tissue

    Very rarely: myalgia.

    From the genitourinary system

    Often: candidal vaginitis.

    Rarely: vaginitis, whites.

    Other reactions

    Rarely: fever, asthenia, generalized pain syndrome, increased sweating.

    From the laboratory indicators

    Sometimes: leukopenia, thrombocytosis, increased concentration alanine aminotransferase (ALT).

    Rarely: increased coagulation time, hyperglycemia, hypokalemia, bilirubinemia, increased concentration of aspartate aminotransferase (ACT), alkaline phosphatase, albuminuria.

    In addition, isolated cases of eosinophilia, thrombocytopenia, decrease of thromboplastin time, thrombocytopathy, increase in lactate dehydrogenase (LDH) concentration, hypoproteinemia and increase in creatinine concentration are described.

    There were also separate reports about the following undesirable phenomena:

    - hemopoiesis: hemolytic anemia, lymphadenopathy;

    · - from the side of water-electrolyte metabolism: dehydration;

    · - from the side of the psyche: dementia, depersonalization, emotional lability, euphoria, hallucinations, thinking disorder, increased libido, collapse;

    · - from the side of the nervous system: amnesia, impaired coordination, muscle hypertonus, meningitis, tremor;

    · - from the side of the organ of vision: weakening of vision, disturbances from the organ of sight, pain in the eyes, blepharitis;

    · - from the cardiovascular system: atrial fibrillation, heart failure, tachycardia, ventricular extrasystole, postural hypotension;

    · - from the gastrointestinal tract: hemorrhagic colitis, ulcerative colitis, gastrointestinal bleeding, glossitis, hiccough, discoloration of the tongue;

    · - from the urinary system: dysuria, pain in the kidney, jade, nocturia, polyuria, urinary incontinence, urinary tract infection;

    · - from the genitourinary system: pain in the mammary glands, menstrual irregularities, metrorrhagia, erectile dysfunction;

    · - other reactions: unpleasant body odor, chills.

    The following adverse reactions were not recorded as adverse events after the administration of cefditoren, but they are characteristic for cephalosporins:

    · - allergic reactions: allergic reactions, including Stevens-Johnson syndrome, multiforme exudative erythema, serum sickness, toxic epidermal necrolysis;

    · - from the urinary system: renal dysfunction, toxic nephropathy;

    · - from the liver and biliary tract: cholestasis;

    · - from the hematopoiesis: aplastic anemia.

    Overdose:
    Symptoms
    When an overdose of the drug in the patient may appear such symptoms as: nausea, vomiting, diarrhea.
    Treatmente
    With the development of a clinical picture of drug overdose, symptomatic therapy is indicated.
    Interaction:

    Antacids

    The combined use of cefeditorin pivoksila and antacids containing magnesium hydroxide, aluminum, after eating reduces the CmOh and AUC cefeditoren by 14% and 11%, respectively. Although the clinical significance of this fact is unknown, it is recommended that the period between the administration of antacids and cefeditorin of the pivocil be 2 hours.

    Probenecid

    Joint use of probenecid and cefeditorin pivoksila reduces the excretion of the antibiotic kidneys, increasing the CmOh by 49%, AUC by 122% and increasing the half-life of cefeditorin by 53%.

    Blockers H2-gistaminovyh receptors

    Simultaneous administration of famotidine intravenously and cefeditorin of pivoxil inward leads to a decrease in the CmOh and AUC by 27% and 22% respectively.Thus, concomitant use of cefeditorin of pivoxyl and H blockers2-gistaminovyh receptors is not recommended.

    Special instructions:
    When developing a hypersensitivity reaction, treatment should be discontinued, and the patient should be prescribed the necessary treatment.
    As with the use of other broad-spectrum antibiotics, treatment with cefditoren may lead to an excessive growth of resistant microflora. For this reason, it is recommended that patients who receive this medication are monitored, especially in the case of prolonged treatment.
    Patients with severe renal failure are advised to periodically monitor kidney function.
    During the course of treatment with cephalosporins, a decrease in prothrombin activity is possible. For this reason, in patients at risk (with renal or hepatic insufficiency or in the case of prior appointment of anticoagulants), prothrombin time control is necessary. The development of diarrhea during or after treatment, especially with its severe, persistent character and the presence of blood impurities, may indicate pseudomembranous colitis.In mild cases of diarrhea, it is enough to just cancel the drug, in more severe cases, antibiotic therapy, to which Clostridium difficile is sensitive, and the purpose of infusion therapy are indicated. Like other cephalosporins, cep can lead to a false positive result of the direct Coombs test, the detection of glucose in the urine using a copper reduction test, but not with the help of an enzyme test. Because of the high risk of false negative results of a ferricyanide glucose test in plasma or blood, it is recommended that patients on the background of cefeditoren treatment to determine the concentration of glucose in blood or plasma use glucose oxidase or glucosehexoquinase methods. When combining cephalosporins with aminoglycosides and / or loop diuretics, especially in patients with impaired renal function, an increased risk of nephrotoxicity may occur.
    Spectracef contains approximately 13.1 mg (for tablets at a dosage of 200 mg) and 26.2 mg (for 400 mg tablets) of sodium in each dose, which should be taken into account when prescribing to patients on a diet low in sodium.
    Effect on the ability to drive transp. cf. and fur:It has not been reported on the effect of cefeditorin on the ability to drive a car and / or other mechanisms. At the same time, it should be taken into account that the reception of Spectracef can be accompanied by such undesirable phenomena as vomiting, headache.
    Form release / dosage:
    Tablets, film-coated, 200 mg.
    Packaging:
    For 10 tablets in blisters from PVC / A1. For 2 or 50 blisters together with instructions for use are put in a cardboard box.
    Tablets, film-coated, 400 mg. For 5 tablets in blisters from PVC / A1. For 2 or 100 blisters together with the instructions for use are placed in a pack of cardboard.
    Storage conditions:In the original packaging at a temperature of no higher than 30 ° C. Keep out of the reach of children.
    Shelf life:
    Dosage of 200 mg: 3 years.
    Dosage of 400 mg: 2 years.
    Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-001420
    Date of registration:12.01.2012
    Date of cancellation:2017-01-12
    The owner of the registration certificate:Meiji Seika Pharma Co., Ltd.Meiji Seika Pharma Co., Ltd. Japan
    Manufacturer: & nbsp
    Representation: & nbspR-PHARM, JSC R-PHARM, JSC Russia
    Information update date: & nbsp02.11.2015
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