Pharmacological properties

Pharmacodynamics

Tsefiksim — an antibiotic of group of cephalosporins of the third generation for intake. in the conditions of in vitro shows considerable bactericidal activity concerning a wide range of gram-positive and gram-negative microorganisms. it is clinically effective at treatment of the infections caused by frequent pathogenic microorganisms including streptococcus pneumoniae, streptococcus pyogenes, e.coli, proteus mirabilis, klebsiella species, haemophilus influenzae (beta and lactamazopositive and - negative), moraxella (branhamella) catarrhalis (beta and lactamazopositive and - negative) and enterobacter species. shows high degree of stability in the presence of a beta laktamaz.

Majority of strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (in particular koagulazopolozhitelny, koagulazootritsatelny and metitsillinrezistentny strains) are resistant

to a tsefiksim. The majority of strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to a tsefiksim.

Pharmacokinetics

Absorption. The bioavailability after oral administration of a tsefiksim is 22–54%. As existence of food considerably does not influence absorption, tsefiksy it is possible to appoint irrespective of meal. The C _max in blood plasma after reception of the recommended doses for adults or children makes from 1.5 to 3 mkg/ml. At repeated dosing there is an insignificant accumulation of a tsefiksim or there is practically no its accumulation. The pharmacokinetics of a tsefiksim was compared at healthy patients of advanced age (at the age of 64 years) and young volunteers (at the age of 11–35 years) after use of 400 mg of a tsefiksim of 1 times a day within 5 days. Average C _max and AUC value were a little higher at elderly people. Patients of advanced age can appoint medicament in the same doses, as well as the adult.

Distribution. Tsefiksim almost completely contacts fraction of albumine, the average free fraction makes about 30%.

Metabolism. Metabolites of a tsefiksim are not allocated from blood plasma or urine of the person.

Removal. Tsefiksim is brought generally in not changed view with urine. The prevailing mechanism is glomerular filtration.

do not have the penetrations of a tsefiksim into breast milk given relatively.

Indication

Infectious and inflammatory diseases caused by microorganisms, sensitive to drug:

• an upper respiratory tract infection (including inflammation of a middle ear) and other upper respiratory tract infections (sinusitis, pharyngitis, tonsillitis of a bacterial etiology) in case of the known or suspected resistance of the activator to other often used antibiotics, or in case of risk of inefficiency of treatment;
• a lower respiratory tract infection (including an acute bronchitis and exacerbation of chronic bronchitis);
• an infection of urinary tract (including cystitis, tsistouretrit, uncomplicated pyelonephritis).

it is Clinically effective at treatment of the infections caused by frequent pathogenic microorganisms including Streptococcus pneumoniae, Streptococcus pyogenes, E.coli, Proteus mirabilis, Klebsiella species, Haemophilus influenzae (beta and lactamazopositive and - negative), Moraxella (Branhamella) catarrhalis (beta and lactamazopositive and - negative) and Enterobacter species. Shows high degree of stability in the presence of a beta laktamaz.

Majority of strains of enterococci (Streptococcus faecalis, group D Streptococci) and Staphylococci (in particular koagulazopolozhitelny, koagulazootritsatelny and metitsillinrezistentny strains) are resistant

to a tsefiksim. The majority of strains of Pseudomonas, Bacteroides fragilis, Listeria monocytogenes and Clostridia are resistant to a tsefiksim.

Use

Meal does not influence absorption of a tsefiksim. duration of a course of treatment depends on disease severity and is established individually. usually the course of treatment makes 7 days, in case of need — 14 days. in the infections caused by streptococcus pyogenes, the course of treatment has to be not less than 10 days. at treatment of uncomplicated cystitis the course of treatment makes 3 days.

Capsule. Adults and children are aged more senior than 12 years with body weight more than 50 kg: the recommended dose makes 400 mg (1 capsule) of 1 times a day.

to

For treatment in an uncomplicated urethral or cervical gonococcal infection recommends once 400 mg.

Patients of advanced age: to appoint in the dose recommended for adults. It is necessary to control function of kidneys and to skorrigirovat a dose in a heavy renal failure (see. Renal failure).

Renal failure: tsefiksy should appoint with care to patients with a renal failure. The dose korrigirutsya taking into account the clearance of creatinine (CC). If KK of ≥60 ml/min., appoint a standard dose if KK of 21-60 ml/min. or at the patients who are on a hemodialysis — 75% of a standard dose with preservation of intervals between use if KK of 20 ml/min. or to the patients who are on peritoneal dialysis to appoint ½ standard doses with preservation of intervals between use. Neither the hemodialysis, nor peritoneal dialysis delete significant quantity of a tsefiksim from an organism.

recommends to appoint

In need of use of medicament in a dose of 400 mg medicament in other dosage form (for example suspensions).

Suspension. Children aged from 6 months up to 10 years with body weight to 50 kg: the recommended dose makes 8 mg/kg of body weight a day for 1 reception or 4 mg/kg each 12 h depending on disease severity.

to Adults and children 10 years are aged more senior than

(or with body weight more than 50 kg): the recommended dose makes 400 mg/days for 1 reception or 200 mg each 12 h depending on disease severity.

to Patients of advanced age to appoint

in the dose recommended for adults. It is necessary to control function of kidneys and to skorrigirovat a dose in a heavy renal failure (see. Renal failure).

Renal failure: tsefiksy it is possible to apply in a renal failure. To patients with clearance of creatinine of ≥20 ml/min. to appoint a usual dose and the mode of dosing. At patients with clearance of creatinine of 20 ml/min. it is recommended to lower a daily dose by 50%. It also touches the faces which are on chronic out-patient peritoneal dialysis or a hemodialysis.

Way of preparation of suspension. Before preparation it is necessary to turn and stir up a bottle to loosen powder. To add boiled cold water to the line (tag) specified on a bottle to 2 receptions, every time shaking up a bottle before formation of uniform suspension.

can Accept suspension not earlier than in 5 min. after preparation.

Before each reception ready suspension should be stirred up carefully.

Contraindication

Confirmed hypersensitivity to antibiotics of group of cephalosporins or other components of drug; hypersensitivity to penicillin; porphyria.

Side effects

Side effects caused tsefiksimy are insignificant

and arise seldom. such disturbances are possible:

from nervous system: headache, dizziness, dysphoria, hyperactivity;

from an organ of hearing and a vestibular mechanism: hearing loss;

from a respiratory system: dispnoe;

from the system of blood and lymphatic system: an eosinophilia, a granulocytopenia, a leukopenia, thrombocytopenia, a thrombocytosis, a neutropenia, hemolytic anemia, a prothrombinopenia (bleedings and bruises without the visible reasons), thrombophlebitis, lengthening of a thrombin and prothrombin time, an agranulocytosis;

from a digestive tract: spasms in a stomach and intestines, an abdominal pain, diarrhea *, nausea, vomiting, candidiasis of a mucous membrane of a mouth, pseudomembranous colitis, dryness in a mouth, dyspepsia, a meteorism, dysbacteriosis, it is rare — stomatitis, a glossitis;

from a metabolism: anorexia;

from a gepatobiliarny system: hepatitis, cholestasia, tranzitorny increase in activity of transaminases of a liver and SF, hyperbilirubinemia, cholestatic jaundice, ikterichnost of scleras, skin ikterichnost;

from kidneys and an urinary system: OPN, including interstitial nephrite as the main morbid condition, a hamaturia;

from the immune system and from skin and hypodermic cellulose: reactions of hypersensitivity, including rash, an itching, a Quincke's disease, an acute anaphylaxis, anaphylactic reactions; reactions similar to a serum disease; medicamentous rash with an eosinophilia and system manifestations (DRESS), a face edema, a dermahemia, urticaria, a multiformny erythema or Stephens's syndrome — Johnson, a serum disease, a purpura, an arthralgia, fever, makulopapulezny and vesicular rashes, fungal dermatitis, peeling of an epithelium, xeroderma, a hair loss, sunblisters, a toxic epidermal necrolysis;

an infection and invasion: vaginal candidiasis (vaginal itching or discharges).

diarrhea Cases after use of a tsefiksim can be connected by

with Clostridium difficile.

This laboratory indicators: the majority of laboratory changes passing have also no clinical value. Increase in urea, increase in creatinine in blood serum, false positive test results of Koombs are possible, positive reaction to ketones in urine in tests using Sodium nitroprussidum, but not with nitroferitsianidy is also possible. Reception of a tsefiksim can lead to false positive glucose tests in urine therefore it is necessary to use fermental tests, changes of indicators of hepatic and renal tests.

General disturbances: perspiration, increased fatigue, weakness, inflammation of a mucous membrane.

* Diarrhea is usually connected by

with use of medicament in high doses. It was reported about diarrhea cases, from moderated to heavy; in that case the termination of therapy is justified. When developing heavy diarrhea the use of a tsefiksim should be stopped.

Special instructions

Heavy skin side reactions, such as toxic epidermal necrolysis, Stephens's syndrome — Johnson, medicamentous rash with an eosinophilia and system manifestations (dress-syndrome), are registered at some patients at use of a tsefiksim. at emergence of heavy skin side reactions use of a tsefiksim it is necessary to stop and appoint the corresponding treatment.

by

At treatment by cephalosporins described cases of medicinal hemolytic anemia, including hard cases with a lethal outcome. Also it was reported about developing of hemolytic anemia after repeated use of cephalosporins (including a tsefiksima).

Influence on function of kidneys. Tsefiksim patients should apply with care with a considerable renal failure (see USE).

As well as at use of other cephalosporins, tsefiksy can lead to OPN, including tubulointerstitsialny nephrite as the main morbid condition. At emergence of OPN use of a tsefiksim it is necessary to stop and appoint the corresponding therapy and/or to take the appropriate measures.

in case of use of a tsefiksim in high doses along with aminoglycosides, polymyxin B, colistin, loopback diuretics (furosemide, Acidum etacrynicum) needs to control function of kidneys carefully. After prolonged use of a tsefiksim it is necessary to control a hematopoiesis.

Reaction of hypersensitivity. Due to hypersensitivity cross-reaction before an initiation of treatment it is necessary to establish whether the patient has in the anamnesis heavy reactions of hypersensitivity to tsefalosporinovy or penicillinic antibiotics. With extra care tsefiksy patients should appoint with hypersensitivity to penicillinic antibiotics as there is a risk of emergence of anaphylactic reaction. If allergic reaction on tsefiksy developed, it is necessary to stop medicament use. The allergic reactions (especially an anaphylaxis) observed at use beta laktamnykh antibiotics can be heavy, and in some cases — with a lethal outcome (see. Side EFFECTS).

Colitis/overgrowth of insensitive microorganisms. At use of medicament there can be side reactions from a digestive tract therefore tsefiksy should appoint with care the patient having in the anamnesis of bleeding, disease of a digestive tract, especially such as ulcer colitis, regional colitis or enteritis and also in an abnormal liver function.

Prolonged use of a tsefiksim can lead

to the excess growth of insensitive microorganisms, including to disturbance of normal intestinal microflora that can lead to Candida albicans overgrowth, and development of candidiasis of a mucous membrane of a mouth (see. Side EFFECTS).

Pseudomembranous colitis. Antibiotics of a broad spectrum of activity, especially at prolonged use, can cause development of pseudomembranous colitis. Symptoms of pseudomembranous colitis can develop in time or after the treatment termination by antibiotics.

Developing of heavy diarrhea during treatment can be a consequence of development of pseudomembranous colitis. In these cases use of a tsefiksim it is necessary to stop and perform the corresponding examination.

Influence on the system of blood. At use beta laktamnykh antibiotics development of a neutropenia and an agranulocytosis, especially in case of long-term treatment is possible. At development of a neutropenia it is required to stop treatment tsefiksimy.

At prolonged use of medicament (more than 10 days) should control blood test.

Influence on results of serological researches. At use of a tsefiksim Koombs's test can yield false positive results. Also tsefiksy can give the false positive analysis of urine on glucose (see. Side EFFECTS).

Range of antibacterial activity. In the infections caused by a beta and hemolytic streptococcus of group A, the course of treatment has to make not less than 10 days to prevent acute rheumatic fever.

Interaction with alcohol. Cephalosporins increase toxicity of alcohol therefore at treatment tsefiksimy do not recommend to take alcoholic beverages.

Children. To children aged up to 12 years, medicament in the form of capsules is not used. Drug in the form of oral suspension is used at children aged from 6 months. Safety and efficiency of a tsefiksim at children aged up to 6 months are not established therefore use of a tsefiksim for patients of this category is not recommended.

Use during pregnancy and feeding by a breast

is not present

Data on use of medicament during pregnancy. Tsefiksim gets through a placenta. Use of a tsefiksim during pregnancy is possible only when the expected advantage for mother exceeds potential risk for a fruit.

Ability to influence speed of response at control of vehicles or other mechanisms

in general does not influence, but it is necessary to consider possibility of side reactions from central nervous system (for example dizziness) which can cause reduction in the rate of psychomotor reactions, in that case it is required to abstain from control of vehicles or work with other mechanisms.

Interaction

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As well as at use of other cephalosporins, increase in a prothrombin time is registered at some patients therefore the persons performing anticoagulating therapy should be careful.

Tsefiksim should be applied with care at the patients receiving coumarin type anticoagulants, for example potassium warfarin. As tsefiksy can strengthen effect of anticoagulants, increase in a prothrombin time with/without clinical manifestations of bleedings is possible.

Blockers of canalicular secretion (Allopyrinolum, probenetsid, diuretics) raise the C _max a tsefiksima in blood plasma, slowing down discharge of a tsefiksim kidneys that can lead to overdose symptoms.

At the combined use of a tsefiksim with potentially nefrotoksichny substances (aminoglycosides, colistin, polymyxin, Viomycinum) or strong diuretics (Acidum etacrynicum, furosemide) the increased risk of developing a renal failure exists.

Salicylic acid increases the level of a free tsefiksim by 50% owing to movement of a tsefiksim from places of linking with proteins. This effect depends on concentration.

Karbamazepin can cause increase in concentration of a tsefiksim in blood plasma therefore it is reasonable to control this indicator.

Nifedipin increases bioavailability of a tsefiksim, but clinical interaction is not defined.

Potentially, like other antibiotics, at use of medicament the reduction of a reabsorption of estrogen and decrease in efficiency of the combined oral contraceptives can arise.

during treatment tsefiksimy false positive reaction to glucose in urine at use of tablets with sulfate of copper, Benedict or Felinga's solutions is possible

. For definition of glucose in urine it is recommended to use the glyukozooksidazny test.

Tsefalosporinovy antibiotics can give to

false positive direct test of Koombs. It must be kept in mind that positive test of Koombs can be caused by this drug.

Overdose

Symptoms: strengthening of manifestations of side reactions, such as dizziness, nausea, vomiting, diarrhea.

Treatment: gastric lavage, use of antihistamines and glucocorticoids; oxygenotherapy. The hemodialysis or peritoneal dialysis only in insignificant degree promote removal of a tsefiksim from an organism. Symptomatic therapy.

is not present

Specific antidote for treatment at overdose.

Storage conditions

Capsule and dry powder — at a temperature not above 25 °C, ready suspension — in the fridge (to use for 14 days).