Spektratsef

General characteristics. Structure:

Active ingredient: 200 mg or 400 mg цефдиторен (in the form of a tsefditoren of a pivoksil).

Excipients: Mannitolum how many it is necessary, sodium caseinate, croscarmellose sodium, sodium tripolyphosphate, magnesium stearate, Opadray white (a gipromelloza, titanium dioxide, a macrogoal-400), wax of karnaubskiya, ink Opakod blue (% IN IMS 74 OP 50.41 shellac, N-butanol of 24.35%, Lach dioxide of 4.49%, propylene glycol of 2.91%, isopropanol of 4.65%, ammonia, aluminum on the basis of dye of diamond blue FCF of 11.25%, titanium, the solution concentrated 1.94%).

Pharmacological properties:

Pharmacodynamics. Action mechanism. Tsefditorena pivoksit — semi-synthetic beta лактамный an antibiotic, is pro-medicine of a tsefditoren (cephalosporin of the third generation). The mechanism of effect of drug is connected with inhibition of synthesis of a bacterial wall thanks to its affinity with penitsillinsvyazyvayushchy proteins.

Pharmacokinetic / фармакодинамические features. At purpose of drug in a dose of 200 mg 2 times a day its plasma concentration exceeds the minimum overwhelming concentration concerning 90% of microorganisms (MPK90) for Moraxella catarrhalis, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pyogenes and Streptococcus pneumoniae strains, sensitive to penicillin, during not less than 50% of time of a dosing interval. Purpose of a tsefditoren in a dose of 400 mg 2 times a day provides maintenance of its concentration above MPK during 51% of time of a dosing interval that exceeds MPK concerning 50% of microorganisms (MPK50) for Streptococcus pneumoniae, resistant to penicillin.

Resistance mechanisms. Tsefditoren as cephalosporin of the third generation has the general mechanisms of resistance for this group of antibiotics. Resistance of gram-positive microorganisms can be connected with change of penitsillinsvyazyvayushchy protein of Streptococcus pneumoniae and Streptococcus viridans, or emergence of additional penitsillinsvyazyvayushchy protein (RVR2A) in Staphylococcus spp. Tsefditoren is steady against most of the most widespread chromosomal and plasmid beta лактамаз gram-negative bacteria. At the same time, as well as other cephalosporins, цефдиторен it is hydrolyzed by the beta lactamelements of a wide range mediated by plasmids. Besides, as the reason of resistance development chromosomal beta lactamelements at mutant strains of Enterobacter spp can serve., Citrobacter spp., Morganella spp. and Serratia spp. The mechanism of action of a tsefditoren is similar to other tsefalosporinovy antibiotics and differs from the mechanism of action of other groups of antibiotics. In general, cross resistance between tsefditoreny and other groups of antibiotics is noted. Nevertheless, in rare instances some mechanisms of action (for example, connected with impermeability of an inner membrane or with existence of the mechanism of active removal of an antibiotic from a cell) can be similar for all groups of antibiotics. It causes a certain level of resistance to all antibiotics.

Minimum Overwhelming Concentration (MOC). The recommended MPK values for a tsefditoren allowing to classify microorganisms with high, intermediate sensitivity and resistance: sensitive — ≤ 0,5 mkg/ml, with intermediate sensitivity —> 0,5 mkg/ml and <2 mkg/ml, resistant — ≥ 2 mkg/ml.

Sensitivity. Below information on a range of sensitivity of the majority of microorganisms for the approved indications to use is stated.

Prevalence of the acquired resistance can vary depending on a geographical zone, and also at separate activators. For this reason it is desirable to obtain information on sensitivity of microorganisms in a certain region, especially at treatment of a heavy infection. In cases if resistance of activators raises doubts, it is possible to ask for the help the specialist who will estimate expediency of purpose of a tsefditoren in a specific clinical case.

Usually sensitive types (resistance less than 10%, European data). Aerobic gram-positive microorganisms: Streptococci group of C and G. Strains of Staphylococcus aureus1, Streptococcus agalactiae, Streptococcus pneumoniae1-2, Streptococcus pyogenes1, sensitive to Methicillinum.

Aerobic gram-negative microorganisms: Haemophilus influenzae1, Moraxella catarrhalis1, Anaerobic microorganisms: Clostridium perfringes, Peptostreptococcus spp.

Microorganisms with initial resistance to a tsefditoren. Aerobic gram-positive microorganisms: Enterococcus spp., Staphylococcus aureus strains, Steady against Methicillinum.

Aerobic gram-negative microorganisms: Acinetobacter baumanii, Pseudomonas aeruginosa.

Anaerobic microorganisms: Group Bacteroides fragilis, Clostridium difficile.

Others: Chlamydia spp., Mycoplasma spp., Legionella spp.

1 - clinical performance was shown for sensitive activators according to the approved indications.

2 - some strains with high resistance to penicillin can have a hyposensitivity to a tsefditoren. Strains, resistant to a tsefotaksim and a tseftriakson, it is not necessary to consider as sensitive to a tsefditoren.

Gram-negative microorganisms which contain chromosomal beta lactamelements, such as Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Morganella morganii, Serratia marcescens need to be considered as resistant to a tsefditoren, despite their seeming in vitro susceptibility.

Pharmacokinetics. Absorption. After intake of a tsefditoren of a pivoksil it is soaked up in digestive tract and under the influence of esterases it is hydrolyzed to a tsefditoren. Intake of 200 mg of drug after food is followed by achievement of the maximum concentration (Cmax) equal of 2.6 mkg/ml, approximately in 2.5 h whereas reception of 400 mg of drug leads through the same span to achievement of Cmax equal 4.1 mkg/ml. Absolute bioavailability of a tsefditoren after intake in comparison with intravenous administration makes about 15-20%.

Presence of food at digestive tract accelerates absorption of a tsefditoren of a pivoksil that concentration - time" leads to increase in indicators of Cmax and the area under a pharmacokinetic curve "(AUC) for 50% and 70% in comparison with values on an empty stomach respectively.

Linkng with proteins of plasma and distribution. Linkng of a tsefditoren with proteins of plasma makes 88%. After a multiple and single dose of drug pharmacokinetic parameters did not differ; it testifies to lack of cumulation. The volume of distribution of a tsefditoren in the conditions of equilibrium concentration significantly does not differ from this indicator calculated after single introduction; it practically does not depend on the entered dose and always remains within 40-65 l.

After single introduction of 400 mg of drug penetration into a mucous membrane and a secret of bronchial tubes made 60% and 20% of concentration in a blood plasma respectively. Results of introduction of a similar dose and the subsequent assessment of penetration of an antibiotic into intersticial liquid showed to healthy volunteers that after 8 and 12 h concentration of a tsefditoren in intersticial liquid reaches 40% and 56% of a plasma indicator of the area under a pharmacokinetic curve respectively.

Metabolism/removal. Regardless of a dose and duration of treatment to 18% of the entered dose of a tsefditoren it is removed in not changed look by kidneys.

The drug elimination half-life makes about 1.0-1.5 h of plasma. The general clearance with correction on bioavailability makes about 25-30 l/h, renal clearance — about 80-90 ml/min. Researches of a marked tsefditoren at healthy volunteers showed that not soaked up part of drug is removed through intestines, and the big share of a tsefditoren turns into inactive metabolites — P7 and M-OH. In the course of hydrolysis of a tsefditoren of a pivoksil it is formed пивалат which is removed by kidneys in the form of a pivaloylcarnitine conjugate.

Special groups of patients. Floor. The pharmacokinetics of a tsefditoren of a pivoksil has no essential distinctions at the person depending on a floor.

Elderly patients. At purpose of identical doses concentration of a tsefditoren at elderly patients (65 years are aged more senior) slightly higher in comparison with population of adults of middle age; indicators of Cmax and AUC at such patients are about 26% higher and than 33% respectively. Except for cases of a heavy renal and/or liver failure dose adjustment is not required to patients of advanced age.

Renal failures. After repeated introduction of a tsefditoren of a pivoksil in a dose of 400 mg AUC indicators at healthy volunteers and patients with damage of kidneys of varying severity are that.

Function of kidneys	Clearance of creatinine	AUC0-12 (average ± CO1) (нг × h/ml)
Normal	> 80 ml/min.	11349.3 (1900.8)
Renal failure:
Easy	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 - WITH — a standard deviation.

Noted changes of pharmacokinetic parameters of a tsefditoren at patients with renal failures of easy degree are not considered as clinically significant. At patients with a moderate and heavy renal failure the indicator of AUC is about 3 times higher in comparison with healthy volunteers. The data which are available at the moment time do not allow to recommend any doses of drug to the patients who are on a hemodialysis.

Abnormal liver functions. Influence of abnormal liver functions easy and moderate severity on pharmacokinetics of a tsefditoren of a pivoksil after its introduction in a dose of 400 mg includes insignificant increase in the key pharmacokinetic parameters without statistically significant distinctions. Besides, small increase in amount of the drug which is removed kidneys in comparison with healthy volunteers was noted. Similar data at patients with a heavy liver failure are so far not obtained.

Function of a liver	AUC0-12 (an average ± WITH) (нг × h/ml)
Normal	15733.2 (2935.7)
Liver failure
Easy (a class A on Chayld-Pyyu)	17932.4 (4494.2)
Moderated (a class B on Chayld-Pyyu)	17425.1 (5804.2)

Indications to use:

Treatment of the infections caused by microorganisms, sensitive to a tsefditoren:

— upper respiratory tract infections: acute tonzillofaringit, acute antritis;

— infections lower respiratory ways: exacerbation of chronic bronchitis, community-acquired pneumonia;

— uncomplicated infections of skin and hypodermic fatty tissue: phlegmon, contaminated wounds of skin, abscess, folliculitis, impetigo and furunculosis.

Route of administration and doses:

Inside. Tablets should be swallowed entirely, washing down with enough water, preferably after food.

The recommended dose depends on weight of an infection, an initial condition of the patient and potential contagiums.

Adults and children are more senior than 12 years. Acute pharyngotonsillitis, acute antritis and uncomplicated infections of skin and hypodermic fatty tissue: on 200 mg each 12 h within 10 days.

Exacerbation of chronic bronchitis: on 200 mg each 12 h within 5 days.

Community-acquired pneumonia: on 200 mg each 12 h within 14 days. In hard cases each 12 h within 14 days recommend a dose on 400 mg.

Patients of advanced age. For elderly patients, except for cases of a heavy abnormal liver function and/or kidneys, dose adjustment is not required.

Renal failure. With an easy renal failure of dose adjustment it is not required from patients. At patients with a renal failure of moderate severity (clearance of creatinine of 30-50 ml/min.) the recommended dose should not exceed 200 mg twice a day. At patients with a heavy renal failure (clearance of creatinine less than 30 ml/min.) the maximum daily dose should not exceed 200 mg. At the patients who are on a hemodialysis, the recommended dose is not established.

Abnormal liver function. With an easy or moderate abnormal liver function of dose adjustment it is not required from patients (classes A or B on Chayld-Pyyu). At a heavy liver failure (a class C on Chayld-Pyyu) the data allowing to appoint the recommended dose are not received.

Features of use:

Use at pregnancy and feeding by a breast. Pregnancy. Clinical data on use of a tsefditoren of a pivoksil for pregnant women are not obtained. And though researches at animals did not show embriotoksichny or teratogenic effects of drug, Spektratsef it is not necessary to apply during pregnancy unless the expected advantage for mother exceeds potential risk for a fruit.

Lactation period. Data on penetration of a tsefditoren into breast milk are not enough. Therefore at drug use Spektratsef feeding by a breast should be stopped.

Use at abnormal liver functions. With an easy or moderate abnormal liver function of dose adjustment it is not required from patients (classes A or B on Chayld-Pyyu). At a heavy liver failure (a class C on Chayld-Pyyu) the data allowing to appoint the recommended dose are not received.

Use at renal failures. With an easy renal failure of dose adjustment it is not required from patients. At patients with a renal failure of moderate severity (clearance of creatinine of 30-50 ml/min.) the recommended dose should not exceed 200 mg twice a day. At patients with a heavy renal failure (clearance of creatinine less than 30 ml/min.) the maximum daily dose should not exceed 200 mg. At the patients who are on a hemodialysis, the recommended dose is not established.

Use for children. It is contraindicated to children up to 12 years.

Use for elderly patients. For elderly patients, except for cases of a heavy abnormal liver function and/or kidneys, dose adjustment is not required.

Special instructions. At hypersensitivity reaction development treatment should be stopped, and to the patient to appoint necessary treatment.

As well as at use of other antibiotics of a broad spectrum of activity, treatment tsefditoreny can lead to the excess growth of resistant microflora. For this reason observation of the patients receiving this drug, especially in case of prolonged treatment is recommended.

At patients with a heavy renal failure it is recommended to control function of kidneys periodically.

Throughout a course of treatment cephalosporins decrease of the activity of a prothrombin is possible. For this reason at patients from risk group (with a renal or liver failure or in case of the previous purpose of anticoagulants) control of a prothrombin time is necessary.

Development of diarrhea in time or after treatment, especially at its difficult, resistant character and availability of impurity of blood, can testify to pseudomembranous colitis. In mild cases of diarrhea it is enough only drug withdrawal, in heavier therapy is shown by antibiotics to which shows sensitivity of Clostridium difficile, and purpose of infusional therapy.

As well as other cephalosporins, цефдиторен can result in false positive result of direct test of Koombs, detection of glucose in urine by means of the test of recovery of copper, but not by means of the fermental test. Because of high risk of false-negative result of the ferritsianidny test of definition of glucose in plasma or blood it is recommended that against the background of treatment tsefditoreny in blood or plasma to patients applied glyukozooksidazny or glyukozogeksokinazny methods to definition of concentration of glucose.

At a combination of cephalosporins to aminoglycosides and/or loopback diuretics, especially at patients with renal failures, increase in risk of nephrotoxicity is possible.

Spektratsef contains about 13.1 mg (for tablets a dosage of 200 mg) and 26.2 mg (for tablets a dosage of 400 mg) sodium in each dose that the patients who are on a diet with the low content of sodium need to consider at purpose of drug.

Influence on ability to driving of motor transport and to control of mechanisms. It was not reported about influence of a tsefditoren of a pivoksil on ability to drive the car and/or other mechanisms. At the same time it is necessary to consider that administration of drug Spektratsef can be followed by such undesirable phenomena as vomiting, a headache.

Side effects:

The undesirable phenomena given below are listed depending on anatomo-physiological classification and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥1/10), it is frequent (≥1/100 and <1/10), infrequently (≥1/1000 and <1/100), is rare (≥1/10 000 and <1/1 000), is very rare (<1/10 000, including separate cases).

From a metabolism and food: seldom - anorexia.

From a nervous system: often - a headache; seldom - nervousness, dizziness, sleeplessness, drowsiness, frustration of a dream.

From an organ of sight: very seldom - photosensitivity.

From ENT organs: very seldom - pharyngitis, rhinitis, sinusitis, a ring in ears.

From respiratory system, bodies of a thorax and a mediastinum: very seldom - a bronchospasm.

From digestive tract: very often - diarrhea; often - nausea, an abdominal pain, dyspepsia; seldom - a lock, a meteorism, vomiting, candidiasis of an oral cavity, an eructation, pseudomembranous colitis, a xerostomia, a food faddism; very seldom - aphthous stomatitis.

From a liver and biliary tract: seldom - an abnormal liver function.

From skin and a hypodermic fatty tissue: seldom: rash, itch, urticaria.

From a musculoskeletal system and connecting fabric: very seldom - a mialgiya.

From urinogenital system: often: mycotic vulvovaginitis; seldom - a vaginitis, bleach.

Others: seldom - fever, an adynamy, a generalized pain syndrome, the increased perspiration.

From laboratory indicators: sometimes - a leukopenia, a thrombocytosis, increase in concentration of alaninaminotranspherase (ALT); seldom - increase in a blood clotting time, a hyperglycemia, a hypopotassemia, a bilirubinemia, increase in concentration of aspartate aminotransferase (ACT), an alkaline phosphatase, an albuminuria.

Besides, the isolated cases of an eosinophilia, thrombocytopenia, decrease in tromboplastinovy time, trombotsitopatiya, increases in concentration of a lactate dehydrogenase (LDG), a hypoproteinemia and increase in concentration of creatinine are described.

Also separate messages on the following undesirable phenomena arrived. From bodies of a hemopoiesis: hemolitic anemia, lymphadenopathy.

From water and electrolytic exchange: dehydration.

From mentality: dementia, depersonalization, emotional lability, euphoria, hallucinations, disorder of thinking, increase in a libido, collapse.

From a nervous system: amnesia, incoordination, muscle hyper tone, meningitis, tremor.

From an organ of sight: easing of sight, disturbance from an organ of sight, eye pain, a blepharitis.

From cardiovascular system: fibrillation of auricles, heart failure, tachycardia, ventricular premature ventricular contraction, postural hypotension.

From digestive tract: hemorrhagic colitis, ulcer colitis, gastrointestinal bleeding, glossitis, hiccups, language discoloration.

From an urinary system: a dysuria, pain in kidneys, nephrite, a nocturia, a polyuria, an urine incontience, an infection of uric ways.

From urinogenital system: pain in mammary glands, disturbances of a menstrual cycle, a metrorrhagia, erectile dysfunction.

Others: unpleasant smell of a body, fever.

The following side reactions were not recorded as the undesirable phenomena after use of a tsefditoren, however they are characteristic of cephalosporins

Allergic reactions: allergic reactions, including Stephens-Johnson's syndrome, a mnogoformny exudative erythema, a serum disease, a toxic epidermal necrolysis.

From an urinary system: renal failure, toxic nephropathy.

From a liver and biliary tract: cholestasia.

From bodies of a hemopoiesis: aplastic anemia.

Interaction with other medicines:

Antacids. Combined use of a tsefditoren of a pivoksil and the antacids containing magnesium hydroxide, aluminum after food lowers indicators of Cmax and AUC of a tsefditoren by 14% and 11%, respectively. Though clinical value of this fact is unknown, it is recommended that the period between introduction of antacids and a tsefditorena of a pivoksil made 2 h.

Probenetsid. Combined use of a probenetsid and tsefditoren of a pivoksil reduces removal of an antibiotic kidneys, increasing Cmax indicator by 49%, AUC for 122% and increasing an elimination half-life of a tsefditoren by 53%.

Blockers of H2-histamine receptors. Simultaneous administration of famotidine intravenously and a tsefditorena of a pivoksil inside leads to decrease in indicators of Cmax and AUC by 27% and 22% respectively. Thus, simultaneous use of a tsefditoren of a pivoksil and blockers histamine H2 receptors is not recommended.

Contraindications:

— hypersensitivity to a tsefditoren, other cephalosporins or any other component of drug.

— heavy allergic reactions to penicillin and others beta лактамные antibacterial drugs;

— a liver failure of a class C on Chayld-Pyyu;

— to the patients who are on a hemodialysis;

— reactions of hypersensitivity to protein to casein in the anamnesis;

— primary insufficiency of a carnitine;

— children's age up to 12 years;

— simultaneous use of a tsefditoren of a pivoksil and blockers histamine H2 receptors.

With care: to patients with hypersensitivity to others beta лактамным to antibiotics because of a possibility of development of cross allergic reactions; simultaneous use with aminoglycosides and diuretics (furosemide); to patients with GIT pathology (including colitis in the anamnesis).

Overdose:

Symptoms. At overdose of drug the patient can have such symptoms as: nausea, vomiting, diarrhea.

Treatment. At development of a clinical picture of overdose of drug performing symptomatic therapy is shown.

Storage conditions:

To store in original packaging at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity: a dosage of 200 mg - 3 years, a dosage of 400 mg - 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 pieces of tablets in blisters from PVC / aluminum foil, on 2 blisters in packs cardboard.