Moflaxia - instructions for use, dose, side effects, contraindications

The bactericidal effect of moxifloxacin is due to inhibition of bacterial topoisomerases II and IV, which leads to disruption of the processes of replication, repair and transcription of the biosynthesis of the DNA of a microbial cell and, as a consequence, to the death of microbial cells.

The minimum bactericidal concentrations of moxifloxacin are generally comparable to its minimum inhibitory concentrations.

Mechanisms of resistance

Mechanisms that lead to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines, do not affect the antibacterial activity of moxifloxacin.

Cross-resistance between these groups of antibacterial drugs and moxifloxacin is not noted. So far, no cases of plasmid resistance have been observed. The overall frequency of development of resistance is very low (10^-7-10^-10).

Resistance to moxifloxacin develops slowly by multiple mutations. Multiple exposure of moxifloxacin to microorganisms at concentrations below the minimum inhibitory concentration (MIC) is only accompanied by a slight increase in MIC. There are cases of cross-resistance to quinolones. Nevertheless, some gram-positive and anaerobic microorganisms resistant to other quinolones retain sensitivity to moxifloxacin.

It is established that the addition to the structuremolecule moxifloxacin methoxy group in the C8 position increases the activity of moxifloxacin and reduces the formation of resistant mutant strains of Gram-positive bacteria. The addition of the bicycloamine group at the C7 position prevents the development of an active efflux, a mechanism of resistance to fluoroquinolones.

Moxifloxacin in conditions in vitro is active against a wide range of gram-negative and gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical bacteria such as Mycoplasma spp., Chlamydia spp., Legionella spp., and also bacteria resistant to β-lactam and macrolide antibiotics.

Influence on human intestinal microflora

In two studies conducted on volunteers, the following changes in the intestinal microflora were observed after taking moxifloxacin inside. There was a decrease concentrations Escherichia coli, Bacillus spp ... Bacteroides vulgatus, Enterococcus spp., Klebsiella spp., as well as anaerobes Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp. These changes were reversible within two weeks. Toxin Clostridium difficile Not found.

In Vitro Sensitivity Testing

The spectrum of antibacterial activity of moxifloxacin includes the following microorganisms:

Sensitive	Moderately sensitive	Resistant
Gram-positive
Gardnerella vaginalis
Streptococcus pneumoniae * (including strains resistant to penicillin and strains with multiple antibiotic resistance), as well as strains resistant to two or more antibiotics, such as penicillin (MIC ≥ 2 μg / ml), second-generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, trimethoprim / sulfamethoxazole
Streptococcus pyogenes (group A) *
Group Streptococcus milleri (S. anginosus , S. constellatus and S. intermedius *)
Group Streptococcus viridans (S. viridans, S..mutans, S.mitis, S. sanguinis, S. salivarius, S. thermophilus, S. constellatus)
Streptococcus agalactiae
Streptococcus dysgalactiae
Staphylococcus aureus (methicillin-sensitive strains) *		Staphylococcus aureus (methicillin / moxifloxacin resistant strains)⁺
Coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), methicillin-sensitive strains		Coagulase-negative staphylococci (S. cohnii, S. epidermidis, S. haemolyticus, S. hominis, S. saprophyticus, S. simulans), methicillin-resistant strains
	Enterococcus faecalis * (only strains sensitive to vancomycin and gentamicin)
	Enterococcus avium*
	Enterococcus faecium*
Gram-negative
Haemophilus influenzae (including strains producing and non-producing β-lactamases) *
Haemophilus parainfluenzae *
Moraxella catarrhal is (including strains producing and non-producing β- lactamase) *
Bordetella pertussis
Legionella pneumophila	Escherichia coli *
Acinetobacter baumanii	Klebsiella pneumoniae *
	Klebsiella oxytoca
	Citrobacter freundii*
	Enterobacter spp. (E. aero genes, E. intermedius, E. sakazaki)
	Enterobacter cloacae *
	Pantoea agglomerans
		Pseudomonas aeruginosa
	Pseudomonas fluorescens
	Burkholderia cepacia Stenotrophomonas maltophilia
	Proteus mirabilis *
Proteus vulgaris
	Morganella morganii
	Neisseria gonorrhoeae *
	Providencia spp. (P. rettgeri, P. stuartii)
Anaerobes
	Bacteroides spp. (B. fragilis , B. distasoni , B. thetaiotaomicron , B. ovatus , B. uniformis* B. vulgaris *)
Fusobacterium spp.
	Peptostreptococcus spp. *
Porphyromonas spp.
Prevotella spp.
Propionibacterium spp.
	Clostridium spp. *
Atypical
Chlamydia pneumonia *
Chlamydia trachomatis *
Mycoplasma pneumoniae *
Mycoplasma hominis
Mycoplasma genitalium
Legionella pneumophila *
Coxiella burnetii

* Sensitivity to moxifloxacin is confirmed by clinical data.

⁺ Moflaxia is not recommended for the treatment of infections caused by strains S. aureus, resistant to methicillin (MRSA). In the case of suspected or confirmed infections caused by MRSA, should be prescribed treatment with appropriate antibacterial drugs.

For certain strains, the spread of acquired resistance may vary depending on the geographical region and over time. In this regard, when testing the sensitivity of a strain, it is desirable to have local information on resistance, especially when treating severe infections.

If patients undergoing treatment in a hospital, the area under the pharmacokinetic curve "concentration-time" (AUC) / MIC₉₀, exceeds 125, and the maximum concentration in the blood plasma (FROM_mOh)/MIC₉₀ is within the range of 8-10, this implies a clinical improvement. In outpatients, the values of these surrogate parameters are usually less: AUC / MIC₉₀> 30-40.

Parameter (average value)	*AUIC (h)**	FROM_mOh/ MIC₉₀
MIC₉₀ 0,125 mg / l	279	23,6
MIC₉₀ 0.25 mg / l	140	11,8
MIC₉₀ 0.5 mg / l	70	5,9

*AUIC (h) is the area under the inhibitory curve (ratio AUIC / MIC₉₀)

Pharmacokinetics:

Suction

Ingestion moxifloxacin absorbed quickly and almost completely. Absolute bioavailability is about 91%.

The pharmacokinetics of moxifloxacin when administered at a dose of 50 to 1200 mg once, and also at 600 mg / day for 10 days is linear. The equilibrium state is reached within 3 days.

After a single application of 400 mg of moxifloxacin FROM_max in blood plasma is achieved within 0.5-4 hours and is 3.1 mg / l. After taking 400 mg of moxifloxacin once a day Css_max and Css_min (maximum and minimum equilibrium concentrations) are 3.2 mg / L and 0.6 mg / L, respectively.

When moxifloxacin is taken with food, there is a slight increase in the time to reach C_m_Oh (for 2 hours) and a slight decrease in C_m_Oh (by about 16%), while the duration of suction does not change. However, these data are not clinically relevant, and moxifloxacin can be used regardless of the time of eating.

Distribution

Moxifloxacin is rapidly distributed in tissues and organs and binds to blood plasma proteins (mainly with albumins) by about 45%. The volume of distribution is about 2 l / kg.

High concentrations of moxifloxacin in excess of those in the plasma created in the lung tissue (including epithelial fluid, alveolar macrophages) in the paranasal sinuses (maxillary and ethmoidal labyrinth), nasal polyps, in areas of inflammation (contents blistering of skin lesions ). In the interstitial fluid and in the saliva moxifloxacin is determined in a free, not protein-related form, at a concentration higher than in the blood plasma. In addition, high concentrations of moxifloxacin are determined in the tissues of the abdominal cavity, peritoneal fluid and female genital organs.

Metabolism

Moxifloxacin undergoes biotransformation of the 2nd phase and is excreted from the body by the kidneys, and also through the intestine, both in unmodified form and in the form of inactive sulfo compounds (M1) and glucuronides (M2). Moxifloxacin does not undergo biotransformation by the microsomal system of cytochrome P450. Metabolites M1 and M2 are present in blood plasma at concentrations lower than the parent compound. According to the results of preclinical studies, it was proved that these metabolites do not have a negative impact on the body in terms of safety and tolerability.

Excretion

The half-life of moxifloxacin is approximately 12 hours. The average total clearance after administration in a dose of 400 mg is 179-246 ml / min. Kidney clearance is 24-53 ml / min. This indicates a partial tubular reabsorption of moxifloxacin.

The mass balance of the initial compound and metabolites of the 2nd phase is about 96-98%, which indicates the absence of oxidative metabolism. About 22% of a single dose (400 mg) is excreted unchanged by the kidneys, about 26% - through the intestine.

Pharmacokinetics in different patient groups

Age, gender and ethnicity

When studying the pharmacokinetics of moxifloxacin in men and women, differences were found in 33% of the indicators AUC and C_m_Oh. Absorption of moxifloxacin did not depend on sex. Differences in indicators AUC and C_m_Oh were due to the difference in weight rather than sex and are not considered clinically significant.

There were no clinically significant differences in the pharmacokinetics of moxifloxacin in patients of different ethnic groups and ages.

Children

The pharmacokinetics of moxifloxacin in children have not been studied.

Impaired renal function

There were no significant changes in the pharmacokinetics of moxifloxacin in patients with impaired renal function (including patients with creatinine clearance (CK) <30 mL / min / 1.73 m²) and in patients on continuous hemodialysis and long-term outpatient peritoneal dialysis.

Impaired liver function

There were no significant differences in the concentration of moxifloxacin in patients with hepatic impairment (Child-Pugh class A and B) compared to healthy volunteers and patients with normal liver function.

Indications:

Infectious-inflammatory diseases caused by micro-organisms sensitive to moxifloxacin:

- acute sinusitis;

- exacerbation of chronic bronchitis;

- uncomplicated infections of the skin and subcutaneous structures;

- Community-acquired pneumonia, including community-acquired pneumonia, caused by strains of microorganisms with multiple antibiotic resistance *;

- complicated infections of the skin and subcutaneous structures (including an infected diabetic foot);

- Complicated intra-abdominal infections, including polymicrobial infections, including intraperitoneal abscesses;

- uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis).

* Streptococcus pneumoniae with multiple antibiotic resistance include strains,resistant to penicillin, and strains resistant to two or more antibiotics from groups such as penicillins (with MIC ≥ 2 μg / ml), second-generation cephalosporins (cefuroxime), macrolides, tetracyclines and trimethoprim / sulfamethoxazole. It is necessary to take into account the current official guidelines on the rules for the use of antibacterial agents.

Contraindications:

- Hypersensitivity to moxifloxacin, other quinolones or any other component of the drug;

- age to 18 years;

- pregnancy and the period of breastfeeding;

- the presence in the anamnesis of a pathology of tendons, developed as a result of antibiotic treatment of the quinolone series;

- in preclinical and clinical studies after administration of moxifloxacin, a change in the electrophysiological parameters of the heart was observed, expressed in the lengthening of the interval QT. In this regard, the use of moxifloxacin is contraindicated in patients of the following categories: congenital or acquired documentary lengthening interval QT, electrolyte disorders, especially uncorrected hypokalemia, clinically significant bradycardia,clinically significant chronic heart failure with a reduced fraction of the left ventricular ejection, the presence of a history of rhythm disorders, accompanied by clinical symptoms;

- moxifloxacin can not be used with other drugs that extend the interval QT;

- Due to the limited number of clinical data, the use of moxifloxacin is contraindicated in patients with impaired liver function (Child-Pugh class C) and in patients with increased transaminase activity more than five times the upper limit of the norm.

Carefully:

- In diseases of the central nervous system (CNS) (including when suspected of involvement of the central nervous system), predisposing to the onset of seizures and reducing the threshold of seizure activity;

- use in patients with psychoses and / or with psychiatric illnesses in anamnesis;

- use in patients with potentially proarrhythmic conditions (especially in women and elderly patients), such as acute myocardial ischemia and cardiac arrest;

- use in patients with cirrhosis of the liver;

- Myasthenia gravis gravis;

- simultaneous reception with drugs that reduce the content of potassium;

- use in patients with a genetic predisposition or an actual deficiency of glucose-6-phosphate dehydrogenase.

Pregnancy and lactation:

Pregnancy

Safety of moxifloxacin during pregnancy is not established, therefore its use is contraindicated. Cases of reversible joint damage in children receiving certain quinolones are described, but no evidence of this effect was reported in the fetus (if the mother used it during pregnancy).

In animal studies, reproductive toxicity was identified. The potential risk to humans is unknown.

Like other quinolones, moxifloxacin causes damage to the cartilage of large joints in preterm animals.

Breastfeeding period

In preclinical studies, it was found that a small amount of moxifloxacin is excreted into breast milk. Data on its use in women during lactation are absent. Therefore, the use of moxifloxacin during breastfeeding is contraindicated.

Dosing and Administration:

Inside, 1 tablet (400 mg) once a day for the infections mentioned above.

Do not exceed the recommended dose.

Tablets should be swallowed whole, without chewing, drinking with a sufficient amount of water, regardless of the time of eating.

Duration of treatment

The duration of treatment is determined by the localization and severity of the infection, as well as the clinical effect:

- exacerbation of chronic bronchitis: 5-10 days;

- acute sinusitis: 7 days;

- uncomplicated infections of the skin and subcutaneous structures: 7 days;

- Community-acquired pneumonia: total duration of stepwise therapy (intravenous administration followed by oral administration) is 7-14 days;

- complicated infections of the skin and subcutaneous structures: the total duration of stepwise therapy with moxifloxacin (intravenous administration followed by oral administration) is 7-21 days;

- complicated intra-abdominal infections: the total duration of the stepwise therapy (intravenous administration followed by oral administration) is 5-14 days;

- uncomplicated inflammatory diseases of the pelvic organs: 14 days.

Do not exceed the recommended duration of treatment.

According to clinical studies, the duration of treatment with Moflaxia in tablets can reach 21 days.

Elderly patients

Changes in the dosing regimen in elderly patients are not required.

Children

The efficacy and safety of moxifloxacin in children and adolescents has not been established.

Impaired liver function

Patients with a violation of liver function (classes A and B according to the Child-Pugh classification) are not required to change the dosage regimen (use in patients with cirrhosis of the liver, see section "Special instructions").

Impaired renal function

In patients with impaired renal function (including those with severe renal failure with CR <30 mL / min / 1.73 m²), as well as in patients on continuous hemodialysis and long-term outpatient peritoneal dialysis, changes in the dosing regimen are not required.

Ethnicity

Changes in the dosing regimen in patients of different ethnic groups are not required.

Side effects:

Data on adverse reactions recorded with the use of moxifloxacin 400 mg (by mouth, with stepwise therapy (intravenous administration of moxifloxacin followed by oral administration) and only intravenously) are obtained from clinical studies and post-marketing reports (in italics). Adverse reactions listed in the "often" group occurred at a frequency below 3%, with the exception of nausea and diarrhea.

The frequency was classified as follows: often (from ≥ 1/100 to <1/10), infrequently (from ≥ 1/1000 to <1/100), rarely (from ≥ 1/10000 to <1/1000), very rarely ( <1/10000).

In each group, undesirable effects are listed in descending order of significance.

System-Organ Classes (MedDRA)	Often	Infrequently	Rarely	Rarely
Infectious and parasitic diseases	Fungal superinfections
Violations of the blood and lymphatic system		Anemia Leukopenia Neutropenia Thrombocytopenia Thrombocythemia Prothrombin time extension / increase in the international normalized ratio (INR)	Change in the concentration of thromboplastin in the blood plasma	Increase in prothrombin concentration / decrease in INR
Immune system disorders		Allergic reactions Itchy skin Skin rash Hives Eosinophilia	Anaphylactic / anaphylactoid reactions Angioedema, including laryngeal edema (potentially life-threatening)	Anaphylactic / anaphylactoid shock (including potentially life-threatening)
Disorders from the metabolism and nutrition		Hyperlipidemia	Hyperglycaemia Hyperuricemia	Hypoglycaemia
Disorders of the psyche		Anxiety Psychomotor hyperactivity / agitation	Emotional lability Depression (in very rare cases, behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts) Hallucinations	Depersonalization Psychotic reactions (potentially manifested in behavior with a tendency to self-harm, such as suicidal thoughts or suicidal attempts)
Disturbances from the nervous system	Headache Dizziness	Paresthesia / Dysaestia Disturbances in taste sensitivity (including in very rare cases, agevia) Confusion and disorientation Sleep Disorders Tremor Vertigo Drowsiness	Hypesesia Abnormalities of smell (including anosmia) Atypical dreams Violation of coordination (including gait disturbance due to dizziness or vertigo, in very rare cases leading to trauma from falling, especially in elderly patients) Seizures with various clinical manifestations (including "grand mal" seizures) Violations of attention Violations of speech Amnesia Peripheral neuropathy and polyneuropathy	Hyperesthesia
Disturbances on the part of the organ of sight		Visual impairment (especially with CNS reactions)		Transient loss of vision (especially against the background of reactions from the central nervous system)
Hearing disorders and labyrinthine disorders			Noise in ears Deterioration of hearing, including deafness (usually reversible)
Violations from the heart and blood vessels	Elongation of the QT interval in patients with concomitant hypokalemia	Elongation of the interval QT Heart palpitations Tachycardia Vasodilation	Ventricular tachyarrhythmias Fainting Increased blood pressure Reduction of blood pressure	Nonspecific arrhythmias Polymorphic ventricular tachycardia Cardiac arrest (mainly in persons with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia)
Disturbances from the respiratory system, chest and mediastinal organs		Shortness of breath (including asthmatic conditions)
Disorders from the gastrointestinal tract	Nausea Vomiting Abdominal pain Diarrhea	Reduced appetite and reduced food intake Constipation Dyspepsia Flatulence Gastroenteritis (other than erosive gastroenteritis) Increase in the activity of amylase in the blood plasma	Dysphagia Stomatitis Pseudomembranous colitis (in very rare cases associated with life-threatening complications)
Disturbances from the liver and bile ducts	Increased activity of "liver" transaminases	Dysfunction of the liver (including increased activity of lactate dehydrogenase) Increased bilirubin concentration Increase in activity of gamma-glutamyl transferase Increase in plasma activity of alkaline phosphatase	Jaundice Hepatitis (predominantly cholestatic)	Fulminant hepatitis, potentially leading to life-threatening hepatic insufficiency (including fatal cases)
Disturbances from the skin and subcutaneous tissues				Bullous skin reactions, for example, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening)
Musculoskeletal and connective tissue disorders		Arthralgia Myalgia	Tendonitis Increased muscle tone and cramps Muscle weakness	Tendon tendons Arthritis Gait disorders due to damage to the musculoskeletal system Increased symptoms of myasthenia gravis
Disorders from the kidneys and urinary tract		Dehydration (caused by diarrhea or decreased fluid intake)	Impaired renal function Renal failure (as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing impaired renal function)
General disorders and disorders at the site of administration	Reactions in place of injection / infusion	General malaise Nonspecific Increased sweating Phlebitis / thrombophlebitis at the site of infusion	Edema

The frequency of development of the following adverse reactions was higher in the group receiving the stepwise therapy:

often: increased activity of gamma-glutamyltransferase;

infrequently: ventricular tachyarrhythmias, lowering blood pressure, swelling, pseudomembranous colitis (in very rare cases associated with life-threatening complications), seizures with various clinical manifestations (including "grand mal" seizures), hallucinations, impaired renal function, renal failure (as a result of dehydration, which can lead to kidney damage, especially in elderly patients with pre-existing renal dysfunction).

Overdose:

There are limited data on the overdose of moxifloxacin.No side effects were observed with moxifloxacin at a dosage up to 1200 mg once and 600 mg for 10 days or more.

In case of an overdose, one should be guided by the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring. The use of activated carbon immediately after ingestion can help prevent excessive systemic exposure to moxifloxacin in case of an overdose.

Interaction:

When used simultaneously with atenolol, ranitidine, calcium-containing additives, theophylline, cyclosporine, oral contraceptives, glibenclamide, itraconazole, digoxin, morphine, probenecid (no clinically significant interaction with moxifloxacin was confirmed), dose adjustment is not required.

Drugs that extend the QT interval

It should be taken into account the possible additive effect of lengthening the interval QT moxifloxacin and other drugs that affect the lengthening of the interval QT. Due to the simultaneous use of moxifloxacin and drugs that affect the lengthening of the interval QT, the risk of ventricular arrhythmia, including polymorphic ventricular tachycardia, increases.

Contraindicated simultaneous use of moxifloxacin with the following drugs affecting the lengthening of the interval QT:

- antiarrhythmic drugs class IA (quinidine, hydroquinidine, disopyramide and other);

- antiarrhythmic drugs of class III (amiodarone, sotalol, dofetilide, ibutilide, etc.);

- neuroleptics (phenothiazine, pimozide, sertindole, haloperidol, sultopride, etc.);

- tricyclic antidepressants;

- antimicrobials (sparfloxacin, erythromycin (intravenously), pentamidine, antimalarial drugs, especially halofantrine);

- antihistamines (terfenadine, astemizole, misolastine);

- others (cisapride, wincamine (intravenously), bepridil, difemanyl).

Antacids, multivitamins and minerals

Taking moxifloxacin concomitantly with antacid agents, multivitamins and minerals can lead to a moxifloxacin absorption, due to the formation of chelate complexes with polyvalent cations contained in these preparations. As a result, the concentration of moxifloxacin in the blood plasma can bemuch lower than desired. In this regard, antacid preparations, antiretroviral drugs (for example, didanosine) and other preparations containing magnesium or aluminum, sucralfate and other preparations containing iron or zinc should be used at least 4 hours before or 4 hours after ingestion of moxifloxacin.

Warfarin

With simultaneous application with warfarin, prothrombin time and other parameters of blood coagulation do not change.

Changing the value of INR

In patients who received anticoagulants concomitantly with antibiotics, including moxifloxacin, there are cases of increased anticoagulant activity of anticoagulants. Risk factors are the presence of an infectious disease (and concomitant inflammatory process), the age and general condition of the patient. Despite the fact that there is no interaction between moxifloxacin and warfarin, in patients receiving these drugs simultaneously it is necessary to monitor the INR and, if necessary, adjust the dose of indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin do not have a significant impact on pharmacokinetic parameters of each other. When repeated doses are used moxifloxacin C_m_Oh digoxin in the blood plasma increased by approximately 30%, with the value AUC and the minimum digoxin concentration did not change.

Activated carbon

With the simultaneous use of activated carbon and moxifloxacin at a dose of 400 mg, the systemic bioavailability of moxifloxacin is reduced by more than 80% as a result of reduced absorption. In the case of an overdose, the use of activated carbon at an early stage of absorption inhibits further increase in systemic exposure.

Special instructions:

In some cases, after the first use of the drug may develop hypersensitivity and allergic reactions, which should immediately inform the doctor. Very rarely, even after the first use of the drug, anaphylactic reactions can progress to a life-threatening anaphylactic shock. In these cases, treatment with Moflaxia should be discontinued and immediately begin the necessary medical measures (including anti-shock).

With the use of the drug Mofsaxia, in some patients, lengthening of the interval QT. Moflaxia should be used with caution in women and elderly patients. Because women have a longer interval than men QT, they may be more sensitive to drugs that extend the interval QT. Elderly patients are also more prone to the effects of drugs that affect the interval QT.

Interval lengthening QT is associated with an increased risk of ventricular arrhythmias, including polymorphic ventricular tachycardia.

Degree of lengthening interval QT may increase with an increase in the concentration of moxifloxacin in the blood plasma, therefore, do not exceed the recommended dose. However, in patients with pneumonia, the correlation between the concentration of moxifloxacin in the blood plasma and the lengthening of the interval QT was not noted. None of the 9,000 patients who received moxifloxacin, there were no cardiovascular complications and lethal cases associated with lengthening the interval QT. With the use of Moflaxia, the risk of developing ventricular arrhythmias in patients with predisposing arrhythmias may increase.

In connection with this, the drug Mofslaxia is contraindicated when:

- changes in the electrophysiological parameters of the heart, expressed in the lengthening of the interval QT: congenital or acquired documented lengthening interval QT; Electrolyte disorders, especially with uncorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with a reduced fraction of the left ventricular ejection; presence in the anamnesis of rhythm disturbances, accompanied by clinical symptoms;

- application with other drugs that extend the interval QT (see section "Interaction with other drugs").

Moflaxia should be used with caution:

- in patients with potentially proarrhythmic conditions, such as acute myocardial ischemia and cardiac arrest;

- in patients with cirrhosis of the liver (since this category of patients can not exclude the risk of developing an extension of the interval QT).

When moxifloxacin was taken, cases of fulminant hepatitis, potentially leading to the development of hepatic insufficiency (including fatal cases) were reported (see section "Side effect"). The patient should be informed that,that in case of symptoms of hepatic insufficiency it is necessary to consult a doctor before continuing treatment with Moflaxia.

When moxifloxacin was administered, cases of developing bullous skin lesions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, were reported (see "Side effect" section). The patient should be informed that in case of symptoms of skin or mucous membrane damage, see a doctor before continuing with Moflaxia.

The use of drugs quinolone series is associated with a possible risk of seizures. Moflaxia should be used with caution in patients with CNS diseases and with CNS disorders that predispose to seizures or reduce the threshold of seizure activity.

The use of broad-spectrum antibacterial drugs, including Moflaxia, is associated with a risk of developing pseudomembranous colitis. This diagnosis should be borne in mind in patients who have developed severe diarrhea during treatment with Moflaxia. In this case, immediate therapy should be prescribed.Drugs that inhibit the peristalsis of the intestine are contraindicated in the development of severe diarrhea.

Moflaxia should be used with caution in patients with myasthenia gravis gravis in connection with a possible exacerbation of the disease.

Against the background of quinolone therapy, including moxifloxacin, it is possible to develop tendonitis and tendon rupture especially in elderly patients and patients receiving glucocorticosteroids. Cases which have arisen within several months after the end of treatment are described. With the first symptoms: pain or inflammation at the site of damage, taking the drug Mofslaxia should stop and unload the affected limb.

When applying quinolones, photosensitivity reactions are noted. However, in the conduct of preclinical and clinical studies, as well as with the use of moxifloxacin in clinical practice, there were no photosensitivity reactions.

However, patients receiving Mofslaxia should avoid exposure to direct sunlight and ultraviolet light.

Use of the drug Moflavsia in the form of tablets for oral administration is not recommended in patients with complicated inflammatory diseases of the pelvic organs(for example, associated with tubo-ovarian or pelvic abscesses).

It is not recommended to apply moxifloxacin for the treatment of infections caused by strains Staphylococcus aureus, resistant to methicillin. In the case of suspected or confirmed infections caused by MRSA, appropriate antibiotic preparations should be used for therapy (see the section "Pharmacodynamics").

The ability of moxifloxacin to inhibit the growth of mycobacteria can cause interaction in conditions in vitro moxifloxacin with a Mycobacterium spp., which leads to false-negative results in the analysis of samples of patients treated with Moflaxia during this period.

In patients treated with quinolones, including moxifloxacin, described cases of sensory or sensorimotor polyneuropathy, leading to paresthesia, hypesthesia, dysesthesia or weakness. Patients undergoing treatment with Moflaxia should be warned of the need to seek immediate medical attention before continuing treatment if symptoms of neuropathy occur that include pain, burning, tingling, numbness, or weakness (see "Side effect" section).

Reactions from the psyche may occur even after the first use of fluoroquinolones, including moxifloxacin. In very rare cases, depression or psychotic reactions progress to the occurrence of suicidal thoughts and behavior with a tendency to self-harm, including suicidal attempts (see "Side effect" section). If such reactions develop in patients, Moflaxia should be withdrawn and the necessary measures taken. Care should be taken when using Moflaxia in patients with psychoses and psychiatric illnesses in history.

Due to the wide spread and growing incidence of infections caused by fluoroquinolone resistant Neisseria gonorrhoeae, in the treatment of patients with inflammatory diseases of the pelvic organs, monotherapy with moxifloxacin should not be carried out, except when the presence of a resistant to fluoroquinolones N. gonorrhoeae excluded. If there is no way to exclude the presence of fluoroquinolones resistant N. gonorrhoeae, is necessary resolve the issue of supplementing empirical therapy with moxifloxacin appropriate antibiotic, which is active against N. gonorrhoeae (e.g., cephalosporin).

Disglycemia

As with other fluoroquinolones, a change in blood glucose concentration, including hypoglycemia and hyperglycaemia, was noted with the use of Mofsaxia. On the background of moxifloxacin therapy, disglycemia occurred mainly in elderly patients with diabetes mellitus receiving concomitant therapy with hypoglycemic drugs for oral administration (eg, with sulfonylureas) or insulin. When performing treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended (see section "Side effect").

Effect on the ability to drive transp. cf. and fur:

Fluoroquinolones, including moxifloxacin, can disrupt the ability of patients to drive a car and engage in other potentially dangerous activities requiring increased attention and speed of psychomotor reactions, due to the effects on the central nervous system and visual impairment.

Form release / dosage:

Tablets, film-coated, 400 mg.

Packaging:

For 5, 7 or 10 tablets in a blister of the combined material OPA / Al / PVC - aluminum foil.

For 1 or 2 blisters (5 tablets), or 1 blister (7 tablets), or 1 blister (10 tablets), together with the instruction for use, put in a cardboard box.

For hospitals:

5, 10, 14, 16 or 20 blisters (5 tablets each) or 10 blisters (7 tablets each), or 5, 7, 8 or 10 blisters (10 tablets) together with an equal number of instructions for use are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003587

Date of registration:25.04.2016

Expiration Date:25.04.2021

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp31.05.2018

Illustrated instructions

Instructions

Mofslaxia (Moflaxia)