Moksiftor 400

General characteristics. Structure:

Active ingredient: 400 mg of a moksifloksatsin of a hydrochloride in terms of moxifloxacin in 1 tablet.

Excipients: lactoses monohydrate, silicon dioxide colloid anhydrous, povidone (K-30), sodium of a kroskarmelloz, magnesium stearate.

Cover: talc, titanium dioxide (Е 171), gipromelloza, silicon dioxide colloid anhydrous, field ethylene glycol 6000, ferrous oxide red (Е 172).

Pharmacological properties:

Pharmacodynamics. Moxifloxacin – bactericidal antibacterial drug of a ftorkhinolonovy number of a broad spectrum of activity. Bactericidal effect of drug is caused inhibitory by action of a moksifloksatsin on bacterial to topoisomerase II and IV that death of microbic cells leads to disturbance of biosynthesis of DNA of a microbic cell and, as a result. The minimum bactericidal concentration of drug in general are comparable to its minimum _ng_b_torny concentration.

The mechanisms causing development of resistance to penicillin, cephalosporins, aminoglycosides, macroleads and tetracyclines do not break antibacterial activity of a moksifloksatsin. Cross resistance between these groups of antibacterial drugs and moksifloksatsiny is not noted. Still cases of plasmid resistance were not observed. General frequency of development of resistance very insignificant (10-7-10-10). Resistance to a moksifloksatsin develops slowly by multiple mutations.

Repeated action of a moksifloksatsin on microorganisms in concentration below the minimum inhibiting concentration (MIC) is followed only by insignificant increase in MIK.

Cases of cross resistance to hinolona are noted. However some gram-positive and anaerobic microorganisms, resistant to other hinolona, are sensitive to a moksifloksatsin.

In vitro moxifloxacin is active concerning a wide range of gram-positive and gram-negative microorganisms, anaerobe bacterias, acid resisting and atypical bacteria (Mycoplasma, Chlamidia, Legionella). Moxifloxacin is effective concerning bacteria, resistant to β-laktamny and makrolidny antibiotics.

The range of antibacterial activity of a moksifloksatsin includes the following microorganisms:

- gram-positive – Streptococcus pneumoniae (including strains, resistant to penicillin and macroleads), Streptococcus pyogenes (group A), Streptococcus milleri, Streptococcus mitior, Streptococcus agalactiae, Streptococcus dysgalactiae, 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.

- gram-negative – Haemophilus influenzae (including ß-laktamazonegativn_ and positive strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including ß‑лактамазонегативні 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 ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Fusobacterium 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.

Pharmacokinetics. At oral administration moxifloxacin quickly and almost is completely soaked up from digestive tract. Absolute bioavailability reaches nearly 91%.

In the range of doses of 50-1200 mg at a single dose and in doses on 600 mg a day during 10 days the pharmacokinetics is linear. The steady condition of parameters is reached within three days.

After a single dose of 400 mg the maximum concentration in a blood plasma (Cmax) is reached during 0,5-4 h and makes 3,1 mg/l.

At reception of a moksifloksatsin together with food Smakh is marked out insignificant increase in time of achievement (for 2 hours) and insignificant decrease Smakh (approximately for 16%), at the same time duration of absorption does not change. However these data have no clinical value and drug can be accepted irrespective of meal.

Moxifloxacin is quickly distributed in fabrics and bodies and contacts blood proteins (mainly with albumine) approximately for 45%. The volume of distribution makes about 2 l/kg. Reaches the high concentration exceeding concentration in plasma drug in tissues of lungs (including in alveolar macrophages), a mucous membrane of bronchial tubes, in nasal bosoms and the centers of an inflammation. In intersticial liquid and in saliva moxifloxacin appears in the free, not connected with proteins look, in concentration above, than in plasma.

Moxifloxacin is exposed to biotransformation of the 2nd phase and is removed from an organism by kidneys, and also with excrements both in not changed look, and in the form of inactive sulfospoluk and glucuronides. Moxifloxacin is not exposed to biotransformation I makrosomalnoit system P450 cytochrome.

The elimination half-life of drug makes about 12 hours. The average general clearance after reception in a dose of 400 mg makes 179-246 ml/min. About 19% of a single dose (400 mg) are removed in not changed view with urine and 25% – with excrements.

Pharmacokinetics at special groups of patients. Renal failure. Essential changes of pharmacokinetics of a moksifloksatsin at patients with a renal failure (including 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. At patients with insignificant and moderate abnormal liver functions (a stage And yes In on classification of Chaydl-Pyyu) the pharmacokinetics of a moksifloksatsin does not change. Data on pharmacokinetics of a moksifloksatsin at patients with heavy abnormal liver functions (on classification of Chayld-Pyyu, the stage C) is not present.

Indications to use:

The infections caused by microorganisms, sensitive to drug:

- exacerbation of chronic bronchitis,
- extra hospital pneumonia, including pneumonia which causative agents are strains of microorganisms with multiple resistance to antibiotics *,
- acute sinusitis,
- uncomplicated infections of skin and hypodermic structures.

Uncomplicated inflammatory diseases of bodies of a small pelvis (including infections of an upper part of a reproductive system at women (a uterus, ovaries), including a salpingitis and an endometritis).

The complicated infections of skin and hypodermic structures (including the infected diabetic foot).

The complicated intraabdominal infections, 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 of such groups as penicillin (at the minimum oppressing activity more than 2 mkg/ml), the 2nd generation of cephalosporins (tsefuroksy), macroleads, tetracyclines and Trimethoprimum/sulfamethoxazole.

Route of administration and doses:

Adults. About 1 tablet (400 mg) of a moksifloksatsin in days is recommended to accept. It is not recommended to exceed the specified dose.

Pill should be taken, without chewing, washing down with enough water. Drug can be accepted irrespective of meal time.

Therapy duration. Duration of treatment is defined by disease severity and clinical effect.

Exacerbation of chronic bronchitis – 5 days.

Not hospital pneumonia – 10 days.

Acute sinusitis – 7 days.

Uncomplicated infectious diseases of skin and hypodermic fabrics – 7 days.

Uncomplicated inflammatory diseases of bodies of a small pelvis – 14 days.

The complicated infectious diseases of skin and hypodermic fabrics – the general duration of step therapy moksifloksatsiny (intravenous administration of drug with the subsequent intake) makes 7-21 days.

The complicated intraabdominal infections – the general duration of step therapy (intravenous administration of drug with the subsequent intake) makes 5-14 days.

Patients of advanced age Dose adjustment for patients of advanced age is not required.

Abnormal liver function. Dose adjustment is not required to patients with abnormal liver functions (see also section "Features of Use").

Renal failure. To patients with a renal failure (including at 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, dose adjustment is not necessary.

Features of use:

Use during pregnancy or feeding by a breast. Drug is contraindicated during pregnancy or feeding by a breast. For the period of treatment by drug feeding by a breast should be stopped.

Children. Contraindicated.

It was reported about hypersensitivity and allergic reactions to ftorkhinolona, including moxifloxacin, after the first use. Anaphylactic reactions can progress to a life-threatening acute anaphylaxis even after the first use. In such cases it is necessary to stop administration of drug and to begin the corresponding therapy (for example antishock).

At use of a moksifloksatsin for some patients increase in an interval of QT on the electrocardiogram can be noted.

As at women longer interval of QT in comparison with men is noted, they can be more sensitive to drugs which extend QT interval. Patients of advanced age can be more susceptible to the effects associated with drug on QT interval.

Patients who accept moxifloxacin should use drugs which can lead to decrease in level of potassium with care.

It is necessary to appoint with care moxifloxacin to patients with the proceeding proaritmogenny states (especially to women and patients of advanced age), such as acute ischemia of a myocardium or lengthening of an interval of QT as it can lead to increase in risk of development of ventricular arrhythmias, including "piruetny" ventricular tachycardia ("torsade de pointes"), and a cardiac standstill. 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.

It is necessary to weigh advantage of treatment moksifloksatsiny, especially in cases of infections of low severity, according to information which is stated in the section "Features of Use".

If during treatment arrhythmia symptoms arise drug, it is necessary to stop treatment and to make an ECG.

At use of a moksifloksatsin cases of fulminantny hepatitis were observed, potentially led to a liver failure (including to a lethal outcome). Patients should recommend to see a doctor before continuing treatment if such symptoms and symptoms of fulminantny hepatitis develop as the adynamy is connected with jaundice, quickly develops, dark urine, tendency to bleedings or hepatic encephalopathy

In cases of emergence of symptoms of dysfunction of a liver it is necessary to carry out liver/inspection function monitoring.

It was reported about cases of violent reactions of skin at use of a moksifloksatsin, such as Stephens-Johnson's syndrome or toxic epidermal necrolysis. If there are reactions from skin and/or a mucous membrane, patients should recommend to see immediately a doctor before continuing treatment.

It is known that hinolona can provoke development of convulsive attacks. Moxifloxacin should be applied with care to patients with frustration of TsNS which can cause convulsive attacks or lower a threshold of emergence of the last.

At patients who accepted hinolona, it was reported about cases of touch or touch and motive polyneuropathy that brings to paresthesias, hypesthesias, dizesteziya or weakness. If such symptoms of a neuropathy as pain, burning, a pricking, numbness or weakness develop, patients who receive treatment moksifloksatsiny should report about it to the doctor before continuing treatment.

Due to the use of antibiotics of a broad spectrum of activity, including moksifloksatsin, it was reported about developing of antibiotikassotsiirovanny diarrhea (ASD) and antibiotikassotsiirovavanny colitis (AAK), including pseudomembranous colitis and Clostridium difficile-associated diarrhea which on severity vary from moderate diarrhea to colitis with a lethal outcome. Therefore it is important to weigh a possibility of one diagnosis at patients at whom in time or after use of a moksifloksatsin heavy diarrhea is observed. At suspicion or confirmation of ASD or AAK of treatment by antibacterial agents, including moxifloxacin, it is necessary to stop and to accept immediately the relevant therapeutic activities. Besides, it is necessary to accept the transfers of a disease ought sanitary and epidemic actions for the purpose of reduction of risk. The drugs suppressing a peristaltics are contraindicated to patients at whom heavy diarrhea is observed

Moxifloxacin should be applied with care to patients with a myasthenia гравис in connection with a possibility of an aggravation of symptoms.

During therapy of a hinolonama, including moksifloksatsiny, there can be an inflammation and a rupture of sinews, in particular at patients of advanced age and patients who receive the accompanying therapy by corticosteroids. At the first symptoms of pain or an inflammation patients should stop treatment moksifloksatsiny and to provide rest of the affected extremity (-тям).

It is necessary to apply with care moxifloxacin to patients of advanced age with disorders of functions of kidneys if they cannot provide reception of enough liquid because dehydration can increase risk of developing of a renal failure.

If the vision disorder or other impact on eyes is observed, it is necessary to address the ophthalmologist immediately.

At use of hinolon for patients photosensitivity reactions are noted. However researches showed that moxifloxacin differs in low risk of emergence of photosensitivity. Despite it, it is necessary to recommend to patients to avoid ultra-violet radiation, and long and/or intensive impact of a sunlight during treatment moksifloksatsiny.

Patients with the family or personal anamnesis of insufficiency of activity glyukozo-6-fosfatdegidrogenazy during treatment of a hinolonama have tendency to hemolitic reactions. Therefore such patients should apply moxifloxacin with care.

Patients with rare hereditary problems of intolerance of a galactose, deficit of lactase of Lapp or malabsorption of glucose and a galactose should not accept this drug.

With the complicated inflammatory disease of bodies of a small pelvis (for example, the abscess associated with a pipe ya¾chnikovim or abscess of a small pelvis) for which performing intravenous therapy, treatment by drug Moksiftor 400 in the form of tablets, coated is considered necessary, on 400 mg it is not recommended to patients.

The inflammatory disease of bodies of a small pelvis can be caused by a bacterium of Neisseria gonorrhoeae, resistant to ftorkhinolona. Therefore in such cases it is necessary to appoint empirical use of a moksifloksatsin along with other corresponding antibiotic (for example cephalosporin) if it is impossible to exclude completely risk of development unreceptive to Neisseria gonorrhoeae moksifloksatsin.

If after 3 days of treatment there is no improvement of a clinical state, therapy should be reconsidered.

Moxifloxacin is not recommended for treatment of the infections caused the Methicillinum-resistant golden staphylococcus (MRGS). In case of the suspect or the confirmed infection caused by MRZS it is necessary to begin treatment with the appropriate antibacterial agent.

Ability to influence speed of response at control of motor transport or work with other mechanisms. Ftorkhinolona, including moxifloxacin, can lead to decline in the ability to manage motor transport or to work with other mechanisms because of emergence of reactions from the central nervous system.

Side effects:

Side reactions estimated on emergence frequency: extended (more than 1%, less than 10%), not widespread (more than 0,1%, less than 1%), seldom widespread (more than 0,01%, less than 0,1%), very seldom widespread (less than 0,01%).

Infections: extended – mikotichny superinfection.

From system of a hemopoiesis: not widespread – anemia, a leukopenia, a neutropenia, thrombocytopenia, a trombotsitemiya, lengthening of prothrombin time / increase INR (the international normalized relation), seldom widespread – change of level of thromboplastin, very seldom widespread – increase in level prothrombin/reduction of MNO, change of the prothrombin/MNO level.

From immune system: reactions of acute hypersensitivity: not widespread – the allergic reactions, an itch, rash, urticaria, an eosinophilia seldom widespread – anaphylactic/anaphylactoid reactions, a Quincke's disease, including throat hypostasis (potentially life-threatening), very seldom widespread – an acute anaphylaxis (potentially life-threatening).

Metabolic disturbances: not widespread – a lipidemia, seldom widespread – a hyperglycemia, a hyperuricemia.

From mentality: not widespread – uneasiness reactions, increase in psychomotor activity / the excitement seldom widespread – lability of mood, a depression (in extremely exceptional cases – from possible dangerous behavior, for example, suicide thoughts or attempts of suicide), the hallucinations very seldom widespread – depersonalization, psychotic reactions.

From a nervous system: extended – the headache, dizziness not widespread – paresthesias / дизестезии, taste disturbance (including an ageusia in extremely exceptional cases), confusion of consciousness and loss of orientation, frustration of a dream (preferential sleeplessness), a tremor, вертиго, drowsiness, seldom widespread – a hypesthesia, disturbances of sense of smell (loss of sense of smell), pathological dreams, a lack of coordination (including disturbances of gait owing to dizziness or вертиго, seldom or never – such which lead to injuries as a result of falling, especially at patients of advanced age), convulsive attacks with various clinical manifestations (including grand mal attacks), the disturbance of attention, an alalia, amnesia very seldom widespread – a hyperesthesia.

From organs of sight: not widespread – the vision disorders very seldom widespread – tranzitorny loss of sight.

From acoustic organs: seldom widespread – a ring in ears, a hearing disorder, including deafness (are usually reversible).

From cardiovascular system: widespread – lengthening of a QT interval at patients with a hypopotassemia, not widespread – the strengthened heartbeat, the tachycardia, fibrillation of auricles, stenocardia, a vazodilatation seldom widespread – the ventricular tachyarrhythmias, a short-term loss of consciousness, arterial hypotension / hypertensia very seldom widespread – "piruetny" ventricular tachycardia (torsade de pointes), a cardiac standstill (especially at patients with serious proaritmogenny conditions, such as clinically significant bradycardia, acute ischemia of a myocardium).

From respiratory system: not widespread – an asthma, including an asthmatic state.

From a digestive tract: extended – the nausea, vomiting, a digestive tract pain and in an abdominal cavity, diarrhea not widespread – anorexia, a lock, dyspepsia, a meteorism, a gastroenteritis (including an erosive gastroenteritis), increase in level of amylase, seldom widespread – a dysphagy, the stomatitis associated using an antibiotic colitis (seldom or never associated with complications, life-threatening).

From gepatobiliarny system: extended – increase in level of transaminases, not widespread – abnormal liver functions (including increase in a lactate dehydrogenase), increase in level of bilirubin and gamma глутамилтранспептидазы, increase in serum of an alkaline phosphatase, seldom widespread – the jaundice, cholestatic hepatitis very seldom widespread – fulminantny hepatitis, can potentially lead to development of a life-threatening liver failure (including a lethal outcome).

From skin and hypodermic cellulose: not widespread – a xeroderma; very seldom widespread – violent skin reactions (Stephens-Johnson's syndrome or a toxic epidermal necrolysis, potentially life-threatening).

From a musculoskeletal system: not widespread – the arthralgia, a mialgiya seldom widespread – increase in a muscle tone, myotonia, very seldom widespread – arthritises, disturbance of gait owing to development of symptoms from a musculoskeletal system, an aggravation of symptoms of a myasthenia (myasthenia gravis).

From an urinary system: not widespread – dehydration caused by diarrhea or reduction of consumption of liquid, seldom widespread – a renal failure, a renal failure (owing to dehydration, especially at patients of advanced age and with the accompanying renal failures).

Others: not widespread – the general weakness, nonspecific pain, a hyperhidrosis seldom widespread – hypostasis.

Interaction with other medicines:

For the following substances it was proved lack of clinically significant interaction with moksifloksatsiny: атенолол, ranitidine, calcic additives, theophylline, oral contraceptives, Glibenclamidum, итраконазол, digoxin, morphine, пробенецид. In case of use of these drugs dose adjustment is not necessary.

Antiacid means, minerals and polyvitamins. Use of a moksifloksatsin together with antiacid means, minerals and polyvitamins can lead to disturbance of absorption of drug because of formation of chelate complexes with the polyvalent cations which are contained in these medicines that can cause considerable decrease in their concentration in a blood plasma. Thus, antacids, anti-retrovirus (for example диданозин) and other drugs containing magnesium or aluminum сукральфат and the means containing iron or zinc it is necessary to accept a minimum in 4 hours prior to or in 2 hours after oral administration of a moksifloksatsin.

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

Change of the INR (the international normalized relation) value. At patients who applied anticoagulants in combination with antibiotics including with moksifloksatsiny, increase cases antikoagulyats_yno ї activities were 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 interactions between moksifloksatsiny and warfarin it was not shown by clinical trials, at the patients receiving complex therapy by these drugs it is necessary to carry out monitoring of MNO and if necessary to change a dose of peroral anticoagulant.

Digoxin. The digoxin pharmacokinetics slightly changes under the influence of a moksifloksatsin. After repeated use of a moksifloksatsin for healthy volunteers increase in the maximum concentration of digoxin in a blood plasma approximately for 30% in an equilibrium state without influence on the area under a curve "concentration time" was observed.

Absorbent carbon. At simultaneous use of absorbent carbon and a moksifloksatsin inside in a dose of 400 mg system bioavailability of drug decreases more than by 80% owing to oppression of its absorption of in vivo. Use of absorbent carbon in an early phase of absorption prevents to the further growth of system exposure in overdose cases.

Food and dairy products. Absorption of a moksifloksatsin does not depend on the use of food (including dairy products). Despite it, the antibiotic can be applied irrespective of meal.

Contraindications:

The increased individual sensitivity to any of components of drug or to other antibiotics of group of ftorkhinolon.

The diseases of sinews connected with treatment of a hinolonama in the anamnesis, the inborn or acquired lengthening of an interval of QT, disturbance of electrolytic balance is diagnosed, in particular at нескоригованій hypopotassemias, clinically significant bradycardia; clinically significant heart failure with reduced fraction of emission of a left ventricle, symptomatic arrhythmias in the anamnesis.

Simultaneous use with other drugs which extend QT interval.

Abnormal liver functions (a class C on a scale of Chayld-Pyyu), the level of transaminases more than by 5 times in comparison with the upper bound of norm.

Overdose:

The available data on overdose are limited. Any essential side effects at use of a moksifloksatsin in a dose to 1200 mg were not noted once and on 600 mg within 10 days at healthy volunteers. In case of overdose it is necessary to be guided by a clinical picture and to carry out a symptomatic maintenance therapy and ECG monitoring.

Absorbent carbon can be applied to treatment of overdose at oral administration of drug.

Storage conditions:

Period of validity - 3 years. To store at a temperature not above 30 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 5 tablets in the blister, on 1 blister in a cardboard pack.