Moksiftor

General characteristics. Structure:

Active ingredient: 400 mg of a moksiftor in 1 bottle.

Excipients: a mannitol (Е 421), sodium acetate anhydrous, water for injections.

Antimicrobic broad-spectrum agent.

Pharmacological properties:

Pharmacodynamics. Moxifloxacin – antimicrobic means with a wide range of bactericidal action. In vitro moxifloxacin is effective rather many gram-positive and gram-negative microorganisms, anaerobe bacterias, acid resisting bacteria, and also atypical bacteria (for example Mycoplasma spp., Chlamidia spp., Legionella spp.). It is established that the antibiotic is effective concerning the bacteria steady to β-laktamny and makrolidny drugs.

Moxifloxacin affects the majority of strains of below-mentioned microorganisms.

Gram-positive – Streptococcus pneumoniae (including strains, resistant to penicillin and macroleads and strains with multiple resistance to antibiotics), Streptococcus pyogenes (group A), Streptococcus milleri, Streptococcus mitior, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus, Streptococcus constellatus, Staphylococcus aureus (including strains, sensitive to Methicillinum), Staphylococcus cohnii, Staphylococcus epidermidis (including strains, sensitive to Methicillinum), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus simulans, Corynebacterium diphtheriae, Enterococcus faecalis (only the strains sensitive to Vancomycinum and gentamycin).

Gram-negative – Haemophilus influenzae (including ß-laktamazonegativn_ and positive strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including ß - lactamazonegative and positive strains), Escherichia coli, Enterobacter cloacae, Bordetella pertussis, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter intermedius, Enterobacter sakazaki, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii.

Anaerobe bacterias – Bacteroides distasonis, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides ovatum, Bacteroides thetaiotaomicron, Bacteroides uniformis, Fusobacterium ѕрр., Peptostreptococcus spp., Porphyromonas spp., Porphyromonas anaerobius, Porphyromonas asaccharolyticus, Porphyromonas magnus, Prevotella spp., Propionibacterium spp., Clostridium perfringens, Clostridium ramosum.

Atypical – Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Coxiella burnettii.

Moxifloxacin is less active concerning Pseudomonas aeruginosa, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia.

Bactericidal action of a moksifloksatsin is implemented by its interaction with the bacterial topoisomerases II and IV necessary for replication, recovery and a transcription of DNA.

Activity of a moksifloksatsin depends on its concentration in a blood plasma: the minimum bactericidal concentration usually correspond to the minimum bacteriostatic.

Mechanisms of firmness of the microorganisms inactivating penicillin, cephalosporins, aminoglycosides, macroleads and tetracyclines do not influence antibacterial efficiency of a moksifloksatsin. Cross stability between drug and the specified antibiotics was not noted. Still the resistance mediated by a plasmid was not observed. Very low frequency of development of stability of bacteria is shown (10-7-10-10). At serial dilution of microorganisms it is shown only the insignificant growth of sizes MPK of a moksifloksatsin.

Between antibacterial agents of group of ftorkhinolon cross resistance is usually observed. However some gram-positive and anaerobic microorganisms steady against other hinolona are sensitive to a moksifloksatsin.

Pharmacokinetics. After introduction of 400 mg of a moksifloksatsin the maximum concentration in a blood plasma is defined within 0,5–4 hours. The stable state is reached in three days. Moxifloxacin quickly spreads in vneshnesosudisty space. Bioavailability of drug high, distribution volume is equal in steady state to 2 l/kg. In saliva the highest peak of concentration, than in plasma can be reached. Binding of a moksifloksatsin blood proteins low (45%).

High concentration of a moksifloksatsin take place in tissues of lungs (alveolar macrophages, epithelial liquid, a mucous membrane of bronchial tubes), in saliva and paranasal sinuses, especially in the inflammation centers.

Moxifloxacin is exposed to biotransformation, is removed with urine and bile both in not changed state, and in the form of sulphatic and glyukuronidny conjugates. The average elimination half-life of an antibiotic makes about 12 hours of a blood plasma and saliva.

Absorptions. After single infusion of drug in a dose of 400 mg within 1 hour the maximum concentration (Smakh) is reached at the end of infusion and makes about 4,1 mg/l that corresponds to its increase approximately by 26% concerning the size of this indicator at administration of drug inside. Drug exposure that is defined by AUC indicator (the area under a ratio curve "concentration – time"), slightly exceeds it at administration of drug inside. Absolute bioavailability makes 91%.

After repeated intravenous infusions of drug in a dose of 400 mg within 1 hour Smakh changes in the range from 4,1 mg/l to 5,9 mg/l. The average stable concentration equal to 4,4 mg/l are reached at the end of infusion.

Distribution. Moxifloxacin is quickly distributed in fabrics and bodies and contacts blood proteins (mainly with albumine) for 45%. The volume of distribution makes 2 l/kg.

The high concentration of drug exceeding those in plasma are created in pulmonary fabric (including in alveolar macrophages), a mucous membrane of bronchial tubes, in nasal bosoms, in places of an inflammation (in contents of bubbles at damage of skin). In intersticial liquid and in saliva drug is defined in a form, free, untied with proteins, in the highest concentration, than in plasma. Besides, high concentration of drug are defined in abdominal fabrics and liquids.

Metabolism. Moxifloxacin is exposed to biotransformation and is removed from an organism by kidneys, and also with excrements both in not changed state, and in the form of inactive sulfospoluk and glucuronides. Moxifloxacin does not biotransformirutsya by makrosomalny liver enzymes of system of P450 cytochrome.

Conclusion. The elimination half-life of drug makes 12 hours. The average general clearance after introduction in a dose of 400 mg makes from 179 to 246 ml/min. About 22% of a single dose (400 mg) are removed in not changed state with urine, about 26% – with excrements.

Pharmacokinetics at different groups of patients. Age, sex and ethnic origin. It is not established age and sexual distinctions in pharmacokinetics of a moksifloksatsin. Clinically significant distinctions in pharmacokinetics of a moksifloksatsin at patients of various ethnic groups are not revealed.

Children. The pharmacokinetics of a moksifloksatsin at children was not studied.

Renal failure. Essential changes of pharmacokinetics of a moksifloksatsin at patients with a renal failure (with clearance of creatinine less than 30 ml/min. / 1,73 sq.m) and at being on a continuous hemodialysis and long out-patient peritoneal dialysis are not revealed.

Abnormal liver function. Change of the mode of dosing is not required to patients with an insignificant abnormal liver function (a scale of Chaydl-Pyyu, a stage And yes In). As at patients with heavy abnormal liver functions (Chaydl-Pyyu, a stage C) of a moksifloksatsin is not present data on pharmacokinetics, use of drug for such category of patients is not recommended.

Indications to use:

The infections caused by microorganisms, sensitive to drug:

• extra hospital pneumonia, including extra hospital pneumonia which causative agents are strains of microorganisms with multiple resistance to antibiotics *,
• the complicated infections of skin and hypodermic structures (including the infected diabetic foot),
• the complicated infections of an abdominal cavity, including polymicrobial infections (such as abscessings).

* Streptococcus pneumoniae with multiple resistance to antibiotics include strains, resistant to penicillin and strains, resistant to two or more antibiotics from such groups as penicillin (at the minimum oppressing activity of ≥2 mg/ml), the 2nd generation of cephalosporins (tsefuroksy), macroleads, tetracyclines and Trimethoprimum/sulfamethoxazole.

Route of administration and doses:

The adult appoint 400 mg of 1 times a day at any infections. It is not necessary to exceed the recommended dose.

Treatment duration. Duration of treatment is defined by localization and weight of an infection, and also clinical effect. At the initial stages of treatment it is possible to apply solution of a moksifloksatsin to infusions, and further, in the presence of indications it is possible to appoint drug inside in the form of tablets.

Extra hospital pneumonia: the general duration of step therapy (intravenous administration, intake) – 7-14 days the complicated infections of skin and hypodermic structures: the general duration of step therapy moksifloksatsiny – 7-21 days, the complicated infections of an abdominal cavity: the general duration of step therapy makes 5-14 days.

It is not necessary to exceed the recommended treatment duration.

Correction of the mode of dosing is not required to patients of advanced age.

To patients with an abnormal liver function. Correction of doses of a moksifloksatsin is not required to patients with moderately expressed insufficiency of functions of a liver.

There are no data on safety of use of drug for treatment of patients with a heavy liver failure. Due to the lack of enough clinical data use of a moksifloksatsin to patients with heavy abnormal liver functions (on a scale of Chaydl-Pyyu, the stage C) is not recommended.

To patients with a renal failure (including at heavy degree of a renal failure with clearance of creatinine less than 30 ml/min. / 1,73 sq.m), and also to the patients who are on a continuous hemodialysis and long out-patient peritoneal dialysis, change of the mode of dosing is not required.

At use of drug for treatment of patients of different ethnic groups there is no need for change of the mode of dosing.

The drug is administered intravenously in the form of infusion lasting not less than 60 minutes both in undiluted, and in the diluted look.

Solution of a moksifloksatsin is compatible to such solutions: water for injections, solution of sodium of chloride of 0,9%, chloride sodium solution 1-molar solution of glucose of 5%, solution of glucose of 10%, solution of glucose of 40%, solution of xylitol of 20%, Ringer's solution, Ringer's solution lactat.

Mix of solution of a moksifloksatsin with the above-stated infusion solutions remains stable within 24 hours at the room temperature. Solution should not be frozen or cooled. When cooling solution can pretsipitirovat, at the room temperature precipitated calcium superphosphate is usually dissolved. Solution needs to be stored in an original container at the room temperature. It is necessary to apply only transparent solution.

Features of use:

Use during pregnancy or feeding by a breast. Drug is contraindicated during pregnancy and feeding by a breast.

Children. Efficiency and safety of a moksifloksatsin for children and teenagers are not established therefore drug is not used in pediatric practice.

Features of use. In case of the combined use of infusion solution of a moksifloksatsin and other drugs for intravenous administration each of them should be entered separately. Administration only of transparent infusion solutions of a moksifloksatsin is allowed.

During treatment of a ftorkhinolonama developing of spasms therefore patients should appoint with extra care moxifloxacin with such diseases of the central nervous system which can cause convulsive attacks is possible or lower a threshold of emergence of the last. Correction of doses of a moksifloksatsin is not required to patients with moderately expressed insufficiency of functions of a liver. There are no data on safety of use of drug for treatment of patients with a heavy liver failure. Due to the lack of enough clinical data use of a moksifloksatsin to patients with heavy abnormal liver functions (on a scale of Chaydl-Pyyu, the stage C) is not recommended.

For elderly people and patients with any degree of a renal failure (including at clearance of creatinine of ≤30 ml/min. / 1,73 sq.m) to make changes to the mode of dosing there is no need.

At use of a moksifloksatsin, as well as other ftorkhinolon and macroleads, for some patients insignificant increase in an interval of QT can be noted. In this regard it is necessary to avoid purpose of a moksifloksatsin at patients with lengthening of an interval of QT, with a hypopotassemia, and also that who receives antiarrhytmic drugs of a class ІА (quinidine, procaineamide) or a class ІІІ (Amiodaronum, соталол) as experience of use of a moksifloksatsin to these patients is limited.

It is necessary to appoint drug with care together with drugs which extend QT interval (цизаприд, erythromycin, antipsychotic drugs, tricyclic antidepressants) as the perhaps additive action, and also to the patients inclined to arrhythmias of states, such as bradycardia, acute ischemia of a myocardium.

Extent of lengthening of an interval of QT can raise with increase in concentration of drug therefore it is not necessary to exceed the recommended dose and speed of infusion (400 mg in 60 minutes). Lengthening of an interval of QT is accompanied by the increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.

Against the background of therapy of a ftorkhinolonama, including moksifloksatsiny, especially at patients of advanced age and at those who receive moxifloxacin together with гкс development of a tendovaginitis or a rupture of sinews is possible. At the first symptoms of pain or an inflammation in the place of damage administration of drug it is necessary to stop and unload the affected extremity.

Use of antibacterial drugs of a broad spectrum of activity is accompanied by risk of development of pseudomembranous colitis. On this diagnosis it is necessary to consider at treatment of patients at whom against the background of treatment moksifloksatsiny heavy diarrhea is observed. In this case it is necessary to appoint the corresponding therapy immediately.

In certain cases after the first use of drug hypersensitivity and allergic reactions can develop. It is necessary to see a doctor immediately. Very seldom anaphylactic reactions can progress to a life-threatening acute anaphylaxis even after the first use of drug. In these cases moxifloxacin it is necessary to cancel and hold necessary medical events (including antishock).

At use of a moksifloksatsin for infusion with other drugs each of them should be entered separately.

At use of ftorkhinolon photosensitivity reactions are noted. Therefore the patients receiving moxifloxacin have to avoid direct sunshine and ultra-violet radiation.

Patients who adhere to a diet with the lowered content of salt (at heart failure, a nephrotic syndrome) have to consider that solution for infusions contains sodium chloride.

Bodies which are exposed to the maximum toxic influence of a moksifloksatsin, as well as other ftorkhinolon are the system of a hemopoiesis, the central nervous system and a liver. These changes arise, as a rule, after prolonged treatment moksifloksatsiny in high doses.

Ability to influence speed of response at control of motor transport or work with other mechanisms. Considering possibility of dizziness and drowsiness, it is necessary to abstain from control of motor transport or work with other mechanisms during treatment moksifloksatsiny.

Side effects:

Criteria for evaluation of frequency of development of side reactions of medicine: more than 10% – very frequent, 1-10% – are frequent, 0,1–1% – infrequently, 0,01–0,1% – single, less than 0,01% – rare.

Cardiovascular system: frequent – lengthening of an interval of QT at patients with the accompanying hypopotassemia, infrequently – a cardiopalmus, lengthening of an interval of QT, single – ventricular tachyarrhythmias, arterial hypotension or hypertensia, a syncope, a vazodilatation, is rare – polymorphic ventricular tachycardia (Torsade de Pointes), a cardiac standstill, is preferential at persons with states, inclined to arrhythmias, such as clinically significant bradycardia, acute ischemia of a myocardium.

Alimentary system: frequent – an abdominal pain, nausea, diarrhea, vomiting, dyspepsia symptoms, passing increase in level of transaminases, it is rare – anorexia, a meteorism, a lock, dyspepsia, a gastroenteritis, increase in GGTP (gamma глутамилтранспептидазы), amylases, bilirubin, a tranzitorny abnormal liver function with increase in LDG (lactate dehydrogenase), tranzitorny increase in serum of an alkaline phosphatase, single – a dysphagy, the pseudomembranous colitis (which is seldom associated with the complications menacing for life), jaundice, hepatitis (preferential cholestatic), it is rare – fulminantny hepatitis, it is potentially dangerous by development of a liver failure that it makes threat for life.

Nervous system: frequent – dizziness, a headache, infrequently – paresthesia / дизестезия, disorder of consciousness (confusion, a disorientation), sleeplessness, drowsiness, вертиго, feeling of alarm, a tremor, increase in psychomotor activity, single – a hypesthesia, pathological dreams, a lack of coordination (including disorder of walking as a result of dizziness, seldom or never such that lead to injuries as a result of falling, especially at elderly patients), convulsive attacks with various clinical manifestations (including grand mal attacks), disturbance of attention, an alalia, amnesia, emotional lability, hallucinations, a depression (the behavior with a tendency to self-damage is seldom or never possible), a hypesthesia, rare – a hyperesthesia, depersonalization, psychotic reactions (potentially prove in behavior with a tendency to self-damage).

Infectious complications: often – candidosis superinfection.

Local symptoms: frequent – reactions in the field of an injection (hypostasis, an inflammation, pain, allergic reactions), infrequently – phlebitis/thrombophlebitis.

Organism in general: infrequently – an adynamy, the general weakness, a hyperhidrosis, dehydration (caused by diarrhea or reduction of reception of liquid), rare – pain in the field of a basin, the face edema, a dorsodynia, change of results of laboratory tests, allergic reactions, extremity pain, swelled.

Allergic/anaphylactic reactions: infrequently – urticaria, an itch, rashes, rare – anaphylactic/anaphylactoid reactions, Quincke's diseases, including a face edema, throats, potentially poses a threat for life, are rare – acute/anaphylactoid anaphylaxis (including such which poses a threat for life).

Blood and lymphatic system: infrequently – anemia, a leykotsitopeniya, a thrombocytosis, an eosinophilia, thrombocytopenia, lengthening of prothrombin time / increase INR (the international normalized relation), rare – increase in level prothrombin/reduction of MNO, change of level of a prothrombin and MNO.

Musculoskeletal system: infrequently – an arthralgia, a mialgiya, rare – a tendinitis, myotonia, rare – a rupture of sinews, arthritises, disorders of gait owing to defeat of a musculoskeletal system.

Sense bodys: a visual disturbance – an illegibility, decrease in visual acuity, a diplopia, especially in combination with dizziness and confusion of consciousness, infrequent – taste disturbance (including an ageusia in extremely exceptional cases), rare – a sonitus, disturbances of sense of smell (including loss of sense of smell).

Respiratory system: infrequently – an asthma (including an asthmatic state).

Metabolism: infrequently – a lipidemia, rare – a hyperglycemia, a hyperuricemia.

Urinogenital system: rare – a renal failure as a result of dehydration that can lead to injury of kidneys, especially at elderly patients with the accompanying renal failures.

Skin: seldom – Stephens-Johnson's syndrome or a toxic epidermal necrolysis.

Interaction with other medicines:

Warfarin. At the combined use with warfarin the prothrombin time and other parameters of a blood coagulation do not change.

Change of the INR (the international normalized relation) value. At the patients receiving anticoagulants in combination with antibiotics including with moksifloksatsiny, cases of increase in activity of anti-coagulative drugs are noted. Risk factors are infectious diseases (and the accompanying inflammatory process), age and the general condition of the patient. In spite of the fact that interaction between moksifloksatsiny and warfarin does not come to light, at patients who use these drugs, it is necessary to carry out monitoring of MNO and if necessary to change a dose of peroral antikoagulyats_yny drugs.

Digoxin. Moxifloxacin and digoxin have no significant effect on pharmacokinetic parameters of each other.

Theophylline. Moxifloxacin does not exert any impact on theophylline pharmacokinetics (and vice versa) that demonstrates that moxifloxacin does not interact with 1A2 a subtype of fermental system of P450 cytochrome.

Probenetsid. Probenetsid does not influence the general clearance and renal clearance of a moksifloksatsin. At the combined use of a moksifloksatsin and probenetsid correction of doses is not required.

Antidiabetic drugs. Clinically significant interactions between Glibenclamidum and moksifloksatsiny are not revealed.

Itrakonazol. At the combined use with moksifloksatsiny AUC indicator (the area under a ratio curve "concentration – time") the itrakonazola changes slightly. In turn, итраконазол has also no significant effect on pharmacokinetic parameters of a moksifloksatsin. Therefore at the combined use of these drugs it is not necessary to change the mode of dosing of any of them.

Morphine. Parenteral use of morphine does not reduce bioavailability of a moksifloksatsin.

Oral contraceptives. Interaction between oral contraceptives and moksifloksatsiny is not noted.

Atenolol. The pharmacokinetics of an atenolol slightly changes under the influence of a moksifloksatsin. After reception of a single dose of AUC the atenolola increases approximately by 4%, and Cmax decreases by 10%.

Absorbent carbon. After intravenous administration of drug use of absorbent carbon only slightly reduces system exposure (about 20%).

Contraindications:

The known individual hypersensitivity to any of components of drug or to other antibiotics of group of ftorkhinolon, epilepsy, heavy abnormal liver functions.

Overdose:

Any side effects at use of a moksifloksatsin in a dose to 1200 mg are noted once and on 600 mg within 10 days. In case of overdose it is necessary to be guided by clinical manifestations and to carry out a symptomatic maintenance therapy with ECG monitoring. Use of absorbent carbon for treatment of overdose at an intravenous way of administration of drug has very limited value. It is not known whether peritoneal dialysis or a hemodialysis is effective.

Storage conditions:

Period of validity - 2 years. To store in the place protected from light at a temperature not above 30 °C. Not to freeze. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 100 ml in bottles, on 1 bottle in a plastic bag in a cardboard pack.