Хайнемокс

General characteristics. Structure:

Active ingredient: 436,3 mg of a moksifloksatsin of a hydrochloride that corresponds to 400 mg of a moksifloksatsin.

Excipients: starch corn, lactoses monohydrate, sodium the lauryl sulfate, talc purified magnesium stearate, carboxymethylstarch of sodium, silicon dioxide colloid anhydrous, croscarmellose sodium, cellulose microcrystallic.

Structure of a cover: Opadry white 85G58997 Makc-Colorcon (polyvinyl alcohol, titanium dioxide, talc, macrogoal 3000, lecithin (soy)), ferrous oxide red.

Bactericidal antibacterial drug of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. Moxifloxacin — bactericidal antibacterial drug of a broad spectrum of activity of a ftorkhinolonovy row, 8-metoksiftorkhinolon. Inhibits topoisomerase II and topoisomerase IV, breaks superspiralling and a stitching of ruptures of DNA, suppresses DNA synthesis, causes profound morphological changes in cytoplasm, a cell wall and membranes of sensitive microorganisms. The minimum bactericidal concentration of a moksifloksatsin in general are comparable to its the minimum inhibiting concentration (MIC).

The mechanisms leading to development of stability to penicillin, cephalosporins, aminoglycosides, macroleads and tetracyclines do not break antibacterial activity of a moksifloksatsin. Cross stability between these groups of antibacterial drugs and moksifloksatsiny is not noted. Still also cases of plasmid stability were not observed. The general frequency of development of stability is very insignificant (10-7–10-10). Resistance to a moksifloksatsin develops slowly, by multiple mutations. Repeated impact of a moksifloksatsin on microorganisms in concentration below MIK is followed only by insignificant increase in MIK. Cases of cross resistance to hinolona are noted. Nevertheless, some gram-positive and anaerobic microorganisms, steady against other hinolona, keep sensitivity to a moksifloksatsin.

In vitro moxifloxacin is active concerning a wide range of gram-negative and gram-positive microorganisms, anaerobe bacterias, acid resisting bacteria and atypical bacteria, such as Mycoplasma spp., Chlamydia spp., Legionella spp., and also bacteria, resistant to a beta laktamnym and makrolidny antibiotics.

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

Sensitive. Gram-positive: Gardnerella vaginalis, Streptococcus pneumoniae * (including the strains steady against penicillin and strains, with multiple resistance to antibiotics), Streptococcus pyogenes (group A) *, the Streptococcus milleri group (S. anginosus *, S. constellatus *, S. intermedius *), the Streptococcus viridans group (S. viridans, S. mutans, S. mitis, S. sanguinis, S. salivarius, S. thermophilus, S. constellatus), Streptococcus agalactiae, Streptococcus dysgalactiae, Staphylococcus aureus (including the strains sensitive to Methicillinum) *, koagulazonegativny staphylococcus (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), including the strains sensitive to Methicillinum.

Gram-negative: Haemophilus influenzae (including the strains which are producing and not producing beta lactamelements) *, Haemophilus parainfluenzae *, Moraxella catarrhalis (including the strains which are producing and not producing beta lactamelements) *, Bordetella pertussis, Legionella pneumophila, Acinetobacter baumannii, Proteus vulgaris.

Anaerobe bacterias: Fusobacterium spp., Porphyromonas spp., Prevotella spp., Propionibacterium spp.

Atypical: Chlamydia pneumoniae *, Chlamydia trachomatis *, Mycoplasma pneumoniae *, Mycoplasma hominis, Mycoplasma genitalium, Legionella pneumophila *, Coxiella burnetii.

Moderate and sensitive. Gram-positive: Enterococcus faecalis * (only strains sensitive to Vancomycinum and gentamycin), Enterococcus avium *, Enterococcus faecium*.

Gram-negative: Escherichia coli *, Klebsiella pneumoniae *, Klebsiella oxytoca, Citrobacter freundii *, Enterobacter spp. (E. aerogenes, E. intermedius, E. sakazakii), Enterobacter cloacae *, Pantoea agglomerans, Pseudomonas fluorescens, Burkholderia cepacia, Stenotrophomonas maltophilia, Proteus mirabilis *, Morganella morganii, Neisseria gonorrhoeae *, Providencia spp. (P. rettgeri, P. stuartii).

Anaerobe bacterias: Bacteroides spp. (B. fragilis *, B. distasonis *, B. thetaiotaomicron *, B. ovatus *, B. uniformis *, B. vulgaris *), Peptostreptococcus spp., Clostridium spp.

Resistant. Gram-positive: Staphylococcus aureus (resistant to Methicillinum / офлоксацину strains) **, koagulazonegativny staphylococcus (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), strains, resistant to Methicillinum.

Gram-negative: Pseudomonas aeruginosa.

* Sensitivity to a moksifloksatsin is confirmed with clinical data.

** Use of drug of Haynemoks is not recommended for treatment of the infections caused by strains of S. aureus, resistant to Methicillinum (MRSA). In case of the assumed or confirmed infections caused by MRSA it is necessary to appoint treatment the corresponding antibacterial drugs.

Pharmacokinetics. Absorption. After oral administration moxifloxacin is quickly and almost completely soaked up from a GIT. Meal influences the speed and completeness of absorption a little. Bioavailability — 91%. Cmax of a moksifloksatsin in a blood plasma after intake in a dose of 400 mg makes 3,1 mg/l; Tmax is 0,5–4 h.

Distribution. Moxifloxacin is quickly distributed in fabrics and bodies. Communication with proteins of plasma (it is preferential with albumine) about 45%. Vd makes about 2 l/kg.

The high concentration of a moksifloksatsin exceeding those in plasma are reached in pulmonary fabric (including alveolar macrophages), in mucous bronchial tubes, nasal bosoms, exudate from the center of a skin inflammation. Also high concentration of a moksifloksatsin are created in tissues of abdominal organs, peritoneal liquid and female generative organs. In intersticial liquid and saliva moxifloxacin is defined in the free, not connected with proteins look, in concentration above, than in a blood plasma.

Metabolism. After passing of the 2nd phase of biotransformation moxifloxacin is removed from an organism by kidneys and a GIT both in not changed look, and in the form of inactive sulpho compounds and glucuronides. Moxifloxacin is not exposed to biotransformation microsomal system of P450 cytochrome.

Removal. T1/2 of a moksifloksatsin makes about 12 h. The average general clearance after reception 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 look by kidneys, about 26% — intestines.

Pharmacokinetics at various groups of patients. Age, sex and ethnic origin. At a research of pharmacokinetics of a moksifloksatsin at men and women distinctions in 33% on indicators of AUC and Cmax were revealed. Absorption of a moksifloksatsin did not depend on a floor. Distinctions in indicators of AUC and Cmax were caused rather by a difference in weight, than a floor, and are not considered as clinically significant. Clinically significant distinctions of pharmacokinetics of a moksifloksatsin at patients of various ethnic groups and a different floor 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 (including patients with creatinine Cl <30 ml/min. / 1,73 sq.m) and at the patients who are on a continuous hemodialysis and long out-patient peritoneal dialysis are not revealed.

Abnormal liver function. Concentration of a moksifloksatsin at patients with an abnormal liver function (a class A and B on classification of Chayld-Pyyu) had no essential distinctions in comparison with that at healthy volunteers or patients with normal function of a liver (use for patients with cirrhosis — see. "Contraindication").

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to a moksifloksatsin:

• community-acquired pneumonia, including community-acquired pneumonia which activators are strains of microorganisms with multiple resistance to antibacterial drugs *;
• exacerbation of chronic bronchitis;
• acute bacterial sinusitis;
• the uncomplicated and complicated infections of skin and soft tissues (including the infected diabetic foot);
• the complicated intraabdominal infections, including polymicrobial infections, including intraperitoneal abscesses;
• uncomplicated inflammatory diseases of bodies of a small pelvis (including salpingites and endometritises).

* 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 MIK of ≥2 mkg/ml), generation cephalosporins II (tsefuroksy), macroleads, tetracyclines and Trimethoprimum/sulfamethoxazole.

Route of administration and doses:

Inside, swallowing entirely, not chewing, washing down with enough water, it is desirable after meal. It is not necessary to exceed the recommended dose.

Infection   Community-acquired pneumonia	Dose each 24 h (once a day), mg	Treatment duration, days
	400	7–14
Exacerbation of chronic bronchitis	400	5–10
Acute bacterial sinusitis	400	7
Uncomplicated infections of skin and soft tissues	400	7
The complicated infections of skin and hypodermic structures	400	7–21
The complicated intraabdominal infections	400	5–14
Uncomplicated inflammatory diseases of bodies of a small pelvis	400	14

 

It is not necessary to exceed the recommended treatment duration.

Change of the mode of dosing is not required: at elderly patients; patients with abnormal liver functions (a class A, B on a scale of Chayld-Pyyu); patients with a renal failure (including at heavy degree of a renal failure with Cl of creatinine of ≤30 ml/min. / 1,73 sq.m, and also being on a continuous hemodialysis and long out-patient peritoneal dialysis); patients of various ethnic groups.

Features of use:

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

At use of drug of Haynemoks for some patients lengthening of an interval of QT can be noted. Lengthening of an interval of QT is accompanied by increase in risk of development of ventricular arrhythmias, including polymorphic ventricular tachycardia. There is a direct dependence between increase in concentration of a moksifloksatsin and increase in an interval of QT. Thereof it is not necessary to exceed the recommended dose (400 mg/days).

Elderly patients and women are more sensitive to the drugs extending QT interval. At use of drug of Haynemoks the risk of development of ventricular arrhythmias in patients with the states contributing to arrhythmias can increase. In this regard it is impossible to use drug of Haynemoks in the following cases: the inborn or acquired lengthening of an interval of QT; not corrected hypopotassemia; clinically significant bradycardia; clinically significant heart failure with reduced fraction of emission of a left ventricle; existence in the anamnesis of the disturbances of a cordial rhythm which are followed by clinical symptomatology; a concomitant use of the drugs extending QT interval (including antiarrhytmic drugs of a class of IA, III), etc. (see. "Interaction").

At use of drug of Haynemoks cases of development of the fulminantny hepatitis which is potentially leading to development of a liver failure are noted. At emergence of symptoms of an abnormal liver function it is necessary to see a doctor before continuing treatment by drug.

At administration of drug of Haynemoks it was reported about cases of development of violent damages of skin (Stephens-Johnson's syndrome or a toxic epidermal necrolysis). The patient should be informed that in case of symptoms of damage of skin or mucous membranes it is necessary to see a doctor before continuing administration of drug of Haynemoks.

Use of drugs of a hinolonovy row is accompanied by possible risk of development of spasms. Drug of Haynemoks should be used with care at patients with diseases of TsNS and with the disturbances from TsNS contributing to developing of spasms or reducing a threshold of convulsive activity.

Drug of Haynemoks should be used with care at patients with gravis myasthenia in connection with a possible exacerbation of a disease.

Drug of Haynemoks should be used with care at patients with existence of deficit glyukozo-6-fosfatdegidrogenazy because of possible development of hemolitic reactions.

Use of antimicrobic drugs of a broad spectrum of activity, including drug of Haynemoks, is accompanied by risk of development of pseudomembranous colitis. This diagnosis should be meant at patients at whom against the background of treatment drug of Haynemoks observes heavy diarrhea. In this case it is necessary to cancel drug and to appoint the corresponding therapy. The drugs oppressing an intestines peristaltics are contraindicated at development of heavy diarrhea.

Against the background of therapy of a hinolonama, including moksifloksatsiny, development of a tendinitis and rupture of a sinew, in particular at the elderly patients and patients in parallel receiving GKS is possible. At the first symptoms of pain or an inflammation of sinews it is necessary to stop administration of drug and to immobilize the affected extremity.

Moxifloxacin has no the photosensitizing effect, nevertheless, during treatment drug recommends to avoid UF-radiation, including direct sunshine.

It is not recommended to use moxifloxacin for treatment of the infections caused by Staphylococcus aureus strains, resistant to Methicillinum (MRSA). In case of the assumed or confirmed infections caused by MRSA it is necessary to appoint treatment the corresponding antibacterial drugs (see. "Pharmacodynamics").

Ability of drug of Haynemoks suppress growth of mycobacteria can become the reason of interaction of in vitro of a moksifloksatsin with the test for Mycobacterium spp., resulting in false-negative results in the analysis of samples of patients which to this period carries out treatment by drug of Haynemoks.

At patients to whom treatment of a hinolonama was carried out including drug of Haynemoks, cases of the touch or sensomotor polyneuropathy leading to paresthesias, hypesthesias, dizesteziya or weakness are described. Patients to whom treatment is carried out by drug of Haynemoks should be warned about need of the immediate address to the doctor before continuation of treatment in case of the symptoms of neuropathy including pain, burning, a pricking, numbness or weakness (see. "Side effects").

Reactions from mentality can arise even after the first purpose of ftorkhinolon, including moxifloxacin. Seldom or never the depression or psychotic reactions progress to suicide thoughts and behavior with a tendency to self-damage, including suicide attempts (see. "Side effects"). In case of development in patients of such reactions it is necessary to cancel drug of Haynemoks and to take necessary measures.

Because of wide circulation and the growing incidence of the infections caused resistant to Neisseria gonorrhoeae ftorkhinolona at treatment of patients with inflammatory diseases of bodies of a small pelvis it is not necessary to carry out monotherapy moksifloksatsiny. Except for cases when presence of N. gonorrhоeaе, resistant to ftorkhinolona, is excluded. If there is no opportunity to exclude presence of N. gonorrhоeaе, resistant to ftorkhinolona, it is necessary to resolve an issue of addition of empirical therapy moksifloksatsiny by the corresponding antibiotic which is active concerning N. gonorrhоeaе (for example cephalosporin).

Influence on ability to drive the car and moving mechanisms. Ftorkhinolona, including moxifloxacin, can break ability of patients to drive the car and to be engaged in other potentially dangerous types of activity requiring special attention and speed of psychomotor reactions owing to influence on TsNS and vision disorders.

Side effects:

The listed below undesirable phenomena are specified depending on emergence frequency according to the following gradation: often — from ≥1/100 to <1/10; infrequently — from ≥1/1000 to <1/100; seldom — from ≥1/10000 to <1/1000; very seldom — <1/10000, including separate messages.

From a GIT: often — nausea, vomiting, an abdominal pain, diarrhea; infrequently — a loss of appetite and decrease in consumption of food, a lock, dyspepsia, a meteorism, a gastroenteritis (except an erosive gastroenteritis), increase in activity of amylase; seldom — a dysphagy, stomatitis, pseudomembranous colitis (seldom or never associated with life-threatening complications).

From a liver and biliary tract: often — increase in activity of hepatic transaminases; infrequently — abnormal liver functions (including increase in activity of LDG), increase in concentration of bilirubin, increase in activity of GGT and ShchF; seldom — jaundice, hepatitis (preferential cholestatic); very seldom — the fulminantny hepatitis which is potentially leading to a zhizneugrozhayushchy liver failure.

From CCC: often — lengthening of an interval of QT at patients with the accompanying hypopotassemia; infrequently — lengthening of an interval of QT, a heart consciousness, tachycardia, a vazodilatation (rushes of blood to the person); seldom — ventricular tachyarrhythmias, faints, increase in the ABP, decrease in the ABP; very seldom — nonspecific arrhythmias, polymorphic ventricular tachycardia (torsade de pointes), a cardiac standstill (it is preferential at persons with the states contributing to arrhythmias, such as clinically significant bradycardia, acute ischemia of a myocardium).

From a nervous system: often — a headache, dizziness; infrequently — paresthesias / дизестезии, disturbance/loss of flavoring sensitivity, confusion of consciousness, a disorientation, sleep disorders, a tremor, вертиго, drowsiness; seldom — a hypesthesia, disturbances of sense of smell (including an anosmia), pathological dreams, a lack of coordination (including disturbances of gait because of dizziness or вертиго, seldom or never leading to injuries), spasms with various clinical manifestations (including grand mal), disturbances of attention, disturbance of the speech, amnesia, peripheral neuropathy and polyneuropathy; very seldom — a hyperesthesia.

Mental disorders: infrequently — feeling of alarm, increase in psychomotor activity / agitation; seldom — emotional lability, a depression, hallucinations; very seldom — the depersonalization, psychotic reactions (which are potentially shown in behavior with a tendency to self-damage, including suicide thoughts or suicide attempts).

From an organ of sight: infrequently — vision disorders (especially at reactions from TsNS); very seldom — passing loss of sight (especially against the background of reactions from TsNS).

From an acoustic organ and labyrinth frustration: seldom — a sonitus, deterioration in hearing, including deafness (usually reversible).

From bodies of a hemopoiesis and lymphatic system: infrequently — anemia, a leukopenia, a neutropenia, thrombocytopenia, a trombotsitemiya, lengthening PV/increase in MNO; seldom — change of concentration of thromboplastin; very seldom — increase in concentration prothrombin/reduction of MNO.

From respiratory system, bodies of a thorax and a mediastinum: infrequently — an asthma (including asthmatic states).

From a musculoskeletal system: infrequently — an arthralgia, a mialgiya; seldom — a tendinitis, increase in a muscle tone and a spasm, muscular weakness; very seldom — ruptures of sinews, arthritis, disturbances of gait owing to damage of a musculoskeletal system, strengthening of symptoms of a myasthenia of gravis.

From kidneys and urinary tract: infrequently — dehydration (caused by diarrhea or reduction of reception of liquid); seldom — a renal failure, a renal failure (as a result of dehydration that can lead to injury of kidneys, especially at elderly patients with the accompanying renal failures).

From skin and hypodermic fabrics: very seldom — violent skin reactions, for example Stephens-Johnson's syndrome or a toxic epidermal necrolysis.

From immune system: infrequently — allergic reactions: itch, rash, urticaria, eosinophilia; seldom — anaphylactic/anaphylactoid reactions, a Quincke's disease, including throat hypostasis (potentially life-threatening); very seldom — acute/anaphylactoid anaphylaxis (potentially life-threatening).

From a metabolism: infrequently — a lipidemia; seldom — a hyperglycemia, a hyperuricemia.

Superinfections: often — fungal superinfections.

General frustration: infrequently — a febricula, nonspecific pain, perspiration; seldom — hypostases.

Interaction with other medicines:

There is no clinically significant interaction of a moksifloksatsin with atenololy, ranitidine, kaltsiysoderzhashchy additives, theophylline, peroral contraceptive means, Glibenclamidum, itrakonazoly, digoxin, morphine, probenetsidy. Correction of the mode of dosing at combined use with these drugs is not required.

Antiacid drugs, minerals and polyvitamins. Simultaneous use of a moksifloksatsin and antiacid drugs, minerals and polyvitamins can break absorption of a moksifloksatsin owing to formation of chelate complexes with the polyvalent cations which are contained in these drugs and consequently — to reduce concentration of a moksifloksatsin in a blood plasma. In this regard antiacid, anti-retrovirus drugs (for example диданозин) and other drugs containing magnesium, aluminum, сукральфат, iron, zinc, it is necessary to take at least for 4 h to or in 4 h after intake of a moksifloksatsin.

The drugs extending QT interval. As moxifloxacin influences lengthening of an interval of QT, contraindicated combined use of a moksifloksatsin with the following drugs: antiarrhytmic IA (quinidine, hydroquinidine, Disopyramidum, etc.) and III (Amiodaronum, соталол, дофетилид, ибутилид, etc.) classes; tricyclic antidepressants; neuroleptics (fenotiazina, Pimozidum, сертиндол, haloperidol, сультоприд, etc.); antimicrobic (спарфлоксацин, erythromycin, pentamidine, antimalarial drugs, especially галофантрин); antihistaminic (астемизол, терфенадин, мизоластин) and others (цизаприд, Vincaminum, bepridit, difemanit) means.

Warfarin. At combined use with PV warfarin and other parameters of a blood coagulation do not change. Nevertheless, at the patients receiving anticoagulants in combination with antibiotics including with moksifloksatsiny, cases of increase in anti-coagulative activity of anticoagulative drugs are noted. Risk factors are existence of an infectious disease (and the accompanying inflammatory process), the age and the general condition of the patient. In spite of the fact that interaction between moksifloksatsiny and warfarin is not revealed, at the patients receiving the combined treatment by these drugs it is necessary to carry out monitoring of MNO value and if necessary to adjust a dose of indirect anticoagulants.

Digoxin. Moxifloxacin and digoxin have no significant effect on pharmacokinetic parameters of each other. At use of repeated doses of a moksifloksatsin of Cmax of digoxin increased approximately by 30%, at the same time AUC and Cmin value of digoxin did not change.

Absorbent carbon. At simultaneous use of absorbent carbon and a moksifloksatsin inside in a dose of 400 mg system bioavailability of a moksifloksatsin decreases more than by 80% as a result of braking of its absorption.

GKS. At simultaneous use of a moksifloksatsin and GKS the risk of development of a tendinitis and rupture of sinews increases.

Contraindications:

• hypersensitivity to a moksifloksatsin, other hinolona or other components of drug;
• allergic reactions to a peanut or soy;
• damage of sinews at earlier carried out treatment of a hinolonama;
• concomitant use of the drugs extending QT interval (including antiarrhytmic drugs of a class of IA, III) — see. "Interaction";
• patients with the inborn or acquired documentary lengthenings of an interval of QT; electrolytic disturbances (especially nekorregirovanny hypopotassemia); clinically significant bradycardia; clinically significant heart failure with reduced fraction of emission of a left ventricle; existence in the anamnesis of the disturbances of a rhythm which were followed by clinical symptomatology (use of a moksifloksatsin leads to lengthening of an interval of QT);
• to patients with an abnormal liver function (a class C on classification of Chayld-Pyyu) and increase in activity of transaminases VGN is more than 5 times higher;
• children's age up to 18 years.

With care: the TsNS diseases (including suspicious concerning involvement of TsNS) contributing to developing of spasms and reducing a threshold of convulsive activity; patients with psychoses and mental diseases in the anamnesis; patients with potentially pro-arhythmic states, such as acute ischemia of a myocardium, especially at women and patients of advanced age; gravis myasthenia; cirrhosis; a concomitant use with the drugs reducing the content of potassium.

Overdose:

Treatment: in case of overdose it is necessary to be guided by a clinical picture and to carry out a symptomatic maintenance therapy with ECG monitoring. Purpose of absorbent carbon right after oral administration of drug can help to prevent excessive system influence of a moksifloksatsin in overdose cases.

Storage conditions:

In the dry, protected from light place, at a temperature from 8 to 25 °C. Not to freeze. To store in the place, unavailable to children. A period of validity - 5 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 400 mg. According to 5, 7 or 10 tab. in the blister from It is scarlet / PVC/PVDH or the blister from Is scarlet / the Ave. On 1, 2 or 10 blisters place in a pack cardboard.

For hospitals. According to 100, 500 or 1000 tab. in a package from PVC, a package in bank from PEVP.