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

Excipients: microcrystalline cellulose (136.0 mg), croscarmellose sodium (32.0 mg), lactose monohydrate (68.0 mg), magnesium stearate (6.0 mg), film sheath - hypromellose (9.0-12.6 mg), iron dye red oxide (0.3-0.42 mg), macrogol 4000 (3.0-4.2 mg), titanium dioxide (2.7-3, 78 mg).

Description:

Pink, matte, oblong, biconcave, with a facet of the tablet, covered with a film sheath, engraved with "BAYER"on one side and" M400 "on the other side.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A.14 Moxifloxacin

Pharmacodynamics:

Mechanism of action

Moxifloxacin is a bactericidal antibacterial drug a broad spectrum of action, 8-methoxy fluoroquinolone.

Bactericidal action 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 result, to the death of microbial cells.

Minimal bactericidal the 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. Total frequency development of sustainability is very low (10^-7-10^-10).

Resistance to moxifloxacin develops slowly by multiple mutations.

Multiple effects moxifloxacin on Microorganisms in concentrations below the minimum inhibitory concentration (MIC) is accompanied only by a slight increase in MIC.

There are cases of cross-resistance to quinolones. Nevertheless, some resistant to other quinolones Gram-positive and anaerobic microorganisms preserve sensitivity to moxifloxacin.

It was established that the addition of a molecule moxifloxacin methoxy group in the C8 position increases the activity of moxifloxacin and reduces the formation of resistant mutant strains 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 vitro active against a wide range of gram-negative and gram-positive microorganisms, anaerobes, acid-resistant 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, there were following changes in the intestinal microflora after oral administration moxifloxacin.

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 changesI were reversible within two weeks. Toxin Clostridium difficile Not found.

Sensitivity testing in vitro

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),cephalosporins of the second generation (for example, cefuroxime), macrolides, tetracyclines, trimethoprim / sulfamethoxazole
Streptococcus pyogenes (group A) *
Group Streptococcus milleri (S. anginosus , S. constellatus , and S. intermedins *)
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 / mofloxacin 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 sattarhalis (including strains producing and non-producing β-lactamases) *
Bordetella pertussis
Legionella pneumophila	Escherichia coli *
Acinetobacter baumanii	Klebsiella pneumoniae *
	Klebsiella oxytoca
	Citrobacter freundii *
	Enterobacter spp. (E. aerogenes, 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. uniform is , B. vulgaris )
Fusobacterium spp.
	Peptostreptococcus spp. *
Porphyromonas spp.
Prevotella spp.
Propionibacterium spp.
	Clostridium spp. *
Atypical
Chlamydia pneumoniae*
Chlamydia trachomatis *
Mycoplasma pneumoniae *
Mycoplasma hominis
Mycoplasma genitalium
Legionella pneumophila *
Coxiella burnetii

* Sensitivity to moxifloxacin is confirmed by clinical data.

+ Avelox® is not recommended for the treatment of infections caused by strains S. aureus, resistant to methicillin (MRSA). In the case of alleged 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 (Cmah / 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_m_Oh/ MIC₉₀
MIC₉₀ 0,125 mg / l	279	23,6
MIC₉₀ 0.25 mg / l	140	11,8
MIC₉about 0.5 mg / l	70	5,9

*AUIC is the area under the inhibitory curve (ratio AUC/MANDK₉₀).

Pharmacokinetics:

Suction

When taken orally 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 C_mOh in blood is reached within 0.5-4 hours and is 3.1 mg / l. After taking 400 mg of moxifloxacin 1 time per day Css^max and Css^min 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(at 2 h) and a slight decrease in C_m_Oh(approximately 16%), while the duration of suction does not change. However, these data have no clinical significance, and the drug can be used regardless of food intake.

Distribution

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

High concentrations of moxifloxacin, exceeding those in blood plasma, are created in the lung tissue (including in the epithelial fluid, alveolar macrophages), in the nasal sinuses (maxillary and ethmoid sinuses), in nasal polyps, in foci of inflammation (in the contents of blisters at damage to the skin). 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 is not biotransformed with the cytochrome P450 microsomal system. 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 the drug.

The mass balance of the initial compound and the metabolites of the 2nd phase is approximately 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.

Renal insufficiency

There were no significant changes in pharmacokinetics moxifloxacin in patients with impaired renal function (including patients with creatinine clearance <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 the pathology of the tendons, which developed as a result of the treatment with antibiotics of the quinolone series.

- In preclinical and clinical studies, after the administration of moxifloxacin, a change in the electrophysiological parameters of the heart, 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 heart failure with a reduced fraction of the left ventricular ejection; presence in the anamnesis of rhythm disturbances, accompanied by clinical symptoms.

- Moxifloxacin should not be used with other drugs that extend the interval QT.

- Due to the presence of lactose in the formulation, its administration is contraindicated in congenital lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

- 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 elevated transaminases more than five times the upper limit of the norm.

Carefully:

- In diseases of the central nervous system (including suspicious for involvement of the central nervous system), predisposing to the occurrence of seizures and reducing the threshold of convulsive activity;

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

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

- with myasthenia gravis gravis;

- in patients with cirrhosis;

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

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

Pregnancy and lactation:

Safety of moxifloxacin during pregnancy is not established and 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 has been demonstrated. The potential risk to humans is unknown.

Like other quinolones, moxifloxacin causes damage to the cartilage of large joints in preterm animals. 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 appointment of moxifloxacin during breastfeeding is contraindicated.

Dosing and Administration:

The recommended dosage regimen of moxifloxacin: 400 mg (1 tablet) 1 time per day for the infections mentioned above. Do not exceed the recommended dose.

Tablets should be swallowed whole, not liquid, squeezed with enough water, regardless of food intake.

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: the total duration of the 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 Avelox® 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 impaired hepatic function, changes in the dosing regimen are not required (for use in patients with cirrhosis of the liver, see section "Special instructions").

Renal insufficiency

In patients with impaired renal function (including severe renal failure with creatinine clearance <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.

Application the patients of different ethnic groups

Dosage regimen changes are not required.

Side effects:

Data on adverse reactions recorded with the use of moxifloxacin 400 mg (by mouth, with stepwise therapy [intravenous administration and subsequent oral administration] and only intravenously) are obtained from clinical studies and post-marketing reports (italicized).

Adverse reactions listed in the "frequently" group occurred with a frequency below 3%, except for nausea and diarrhea.

In each frequency group, undesirable drug reactions are listed in order of decreasing significance. The frequency is defined 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).

Systems bodies	Often	Infrequently	Rarely	Highly rarely
Infectious and parasitic diseases	Fungal superinfections
On the part of the hematopoiesis system		Anemia Leukopenia Neutropenia Thrombocytopenia Thrombocythemia Prothrombin time extension / increase in the international normalized ratio (INR)	Change Thromboplastin concentration	Increase prothrombin concentration / decrease INR
From the side immune system		Allergic reactions Itching Rash Hives Eosinophilia	Anaphylactic / anaphylactoid reactions Angioedema, including laryngeal edema (potentially life-threatening)	Anaphylactic / anaphylactoid shock (including potentially life-threatening)
From the side metabolism		Hyperlipidemia	Hyperglycaemia Hyperuricemia	Hypoglycaemia
Mental disorders		Anxiety Psychomotor hyperactivity / agitation	Emotional lability Depression (in very rare cases possibly behavior with a tendency to self-injury, such as suicidal thoughts or suicidal attempts) Hallucinations	Depersonalization Psychotic reactions (potentially manifested in behavior with a tendency to self-injury, such as suicidal thoughts or suicidal attempts)
From the side nervous system	Head pain Dizziness	Paresthesia / Dysaesthesia Disturbances in taste sensitivity (including in very rare cases, agevia) Confusion and disorientation Violations sleep 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
From the side organ of vision		Visual impairment (especially with CNS reactions)		Transient loss of vision (especially against the background of reactions from the central nervous system)
From the side of the hearing organ and labyrinthine disorders			Noise in ears Deterioration hearing, including deafness (usually reversible)
From the side of the cardiovascular system	Interval lengthening QT in patients with concomitant hypokalemia	Elongation of the QT interval Feeling palpitation Tachycardia Vasodilation	Ventricular tachyarrhythmias Fainting Increased blood pressure Reduction of blood pressure	Nonspecific arrhythmias Polymorphic ventricular tachycardia (Torsade de Pointes) Cardiac arrest (mainly in persons with conditions predisposing to arrhythmias, such as clinically significant bradycardia, acute myocardial ischemia)
On the part of the respiratory system, the organs of the thorax and the mediastinum		Shortness of breath (including asthmatic conditions)
From the gastrointestinal tract	Nausea Vomiting Pain in abdomen Diarrhea	Reduced appetite and reduced food intake Constipation Dyspepsia Flatulence Gastroenteritis (other than erosive gastroenteritis) Increase activity of amylase	Dysphagia Stomatitis Pseudomembranous colitis (in very rare cases associated with life-threatening complications)
From the liver and biliary tract	Increased activity of "liver" transaminases	Violations liver function (including increased lactate dehydrogenase activity) Increased bilirubin concentration Increase in activity of gamma-glutamyl transferase Increase in the blood of alkaline phosphatase activity	Jaundice Hepatitis (predominantly cholestatic)	Fulminant hepatitis, potentially leading to life-threatening hepatic insufficiency (including fatal cases)
From the skin and soft tissues				bullous skin reactions, for example, stevensa-jonson syndrome or toxic epidermal necrolysis (potentially life-threatening)
from the musculoskeletal and connective tissue		arthralgia myalgia	tendonitis rise muscle tone and cramps muscular weakness	tendon ruptures arthritis gait disturbance due to musculoskeletal system damage gain symptoms of myasthenia gravis
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 impairment of kidney function)
general disorders and disorders at the injection site	reactions at the injection / infusion site	a common malaise nonspecific pain 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 of arterial pressure, edema, 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 impaired renal function).

Overdose:

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

In case of an overdose focus on the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring.

The use of activated carbon immediately after oral administration of the drug can help prevent excessive systemic exposure to moxifloxacin in cases of overdose.

Interaction:

When combined 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 combined use of moxifloxacin and drugs that affect the lengthening of the interval QT, the risk of developing ventricular arrhythmia increases, including polymorphic ventricular tachycardia (torsade de pointes).

Contraindicated joint use of moxifloxacin with the following drugs that affect the lengthening of the interval QT:

- antiarrhythmic drugs class IA (quinidine, hydroquinidine, disopyramide, etc.);

- 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 may be significantly lower than desired. In this regard, antacids, 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

When combined with warfarin prothrombin time and other parameters of blood coagulation do not change.

Change the value of INR. In patients who received anticoagulants in combination 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. Although the interaction between moxifloxacin and warfarin has not been revealed, in patients receiving concomitant treatment with these drugs, it is necessary to monitor the INR and, if necessary, adjust the dose of indirect anticoagulants.

Digoxin

Moxifloxacin and digoxin do not significantly affect the pharmacokinetic parameters of each other. When repeated doses of moxifloxacin were used, the maximum digoxin concentration increased by approximately 30%, with the area under the concentration-time curve (AUC) and the minimum digoxin concentration did not change.

Activated carbon

With the simultaneous use of activated carbon and moxifloxacin inside at a dose of 400 mg, the systemic bioavailability of the drug is reduced by more than 80% as a result of inhibition of its 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 Avelox® should be discontinued and immediately begin the necessary medical measures (including anti-shock).

With the use of the drug Avelox®, some patients may experience an elongation of the interval QT. Avelox® should be used with caution in women and elderly patients. Since women have a longer QT interval than men, they may be more sensitive to drugs that extend the QT interval. Elderly patients are also more prone to drugs that affect the QT interval.

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

Degree of lengthening interval QT may increase with increasing drug concentration, 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 9000 patients who received Avelox® had cardiovascular complications or lethal cases associated with lengthening the interval QT. When using Avelox®, the risk of developing ventricular arrhythmias in patients with predisposing arrhythmias may increase.

In this regard, the drug Avelox® is contraindicated in:

- 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 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 the section "Interaction with other medicinal products").

Avelox® 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 taking Avelox®, cases of fulminant hepatitis were reported, potentially leading to the development of hepatic insufficiency (including fatal cases) (see section "Side effect"). The patient should be informed that if symptoms of hepatic insufficiency occur, the doctor should be consulted before continuing treatment with Avelox®.

When taking Avellox®, cases of developing bullous skin lesions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (see section "Side effect"). The patient should be informed that if skin or mucous membrane symptoms occur, see a doctor before continuing with Avelox®.

The use of drugs quinolone series is associated with a possible risk of seizures.Avelox® should be used with caution in patients with CNS diseases and with CNS disorders predisposing to the occurrence of seizures or reducing the threshold of convulsive activity.

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

Avelox® 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, tendonitis and tendon rupture are possible especially in the elderly and patients receiving glucocorticosteroids. Cases which have arisen within several months after the end of treatment are described. At the first symptoms of pain or inflammation at the site of damage, taking the drug should stop and unload the affected limb.

When applying quinolones, photosensitivity reactions are noted. However, in pre-clinical and clinical studies, as well as with the use of the drug Avelox®, no photosensitivity reactions were observed in practice. Nevertheless, patients receiving Avelox® should avoid exposure to direct sunlight and ultraviolet light. The use of the drug 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 use moxifloxacin for the treatment of infections caused by strains Staphylococcus aureus resistant to methicillin (MRSA). In the case of suspected or confirmed infections caused by MRSA, should be prescribed treatment with appropriate antibacterial drugs (see the section "Pharmacodynamics"). The ability of Avelox® to inhibit the growth of mycobacteria can cause interaction in vitro moxifloxacin with a Mycobacterium spp., leading to false-negative results in the analysis of samples of patients treated with Avelox® during this period.

Patients treated with quinolones, including Avelox®, described cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypoesthesia, dysesthesia, or weakness. Patients undergoing Avelox® treatment should be cautioned about the need for immediate treatment to the doctor before continuing treatment in case of symptoms of neuropathy, including pain, burning, tingling, numbness or weakness (see section "Side effect").

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 section "Side effect"). If patients develop such reactions, Avelox® should be discontinued and appropriate measures taken. Care should be taken when using Avelox® in patients with psychoses and / or psychiatric illnesses in history.

Because of 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, it is necessary to resolve the issue of supplementing empirical therapy with moxifloxacin appropriate antibiotic, which is active against N. Gonorrhoeae (e.g., cephalosporin).

Disglycemia

As in the case of other fluoroquinolones, the use of the drug Avelox® marked a change in the concentration of glucose in the blood, including hypo- and hyperglycemia. On the background of therapy with the drug Avelox®, disglycemia occurred mainly in elderly patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (eg, sulfonylureas) or insulin. When performing treatment in patients with diabetes mellitus, careful monitoring of the concentration of glucose in the blood is recommended.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 tablets in a foil blister of aluminum and PA / Al / PVC or aluminum foil and PP. For 1 or 2 blisters together with instructions for use in a cardboard pack, or

For 7 tablets in a foil blister of aluminum and PA / Al / PVC or aluminum foil and PP. For 1 blister, along with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012034 / 01

Date of registration:17.05.2010 / 14.01.2013

Expiration Date:Unlimited

The owner of the registration certificate:Bayer Pharma AGBayer Pharma AG Germany

Manufacturer: & nbsp

BAYER PHARMA, AG Germany

Representation: & nbspBAYER, AOBAYER, AO

Information update date: & nbsp21.01.2017

Illustrated instructions

Instructions

Avelox® (Avelox®)