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

Excipients: sodium chloride (2.00 g), hydrochloric acid 1M (0-0.02 g), sodium hydroxide solution 2M (0-0.05 g), water for injection (248.614 -248.664 g).

Description:Pred or yellow solution with a greenish tinge.

Pharmacotherapeutic group:Antimicrobial agent - fluoroquinolone

ATX: & nbsp

J.01.M.A.14 Moxifloxacin

Pharmacodynamics:

Mechanism of action

Moxifloxacin is a bactericidal antibacterial broad-spectrum drug, 8-methoxy fluoroquinolone. The bactericidal effect of moxifloxacin

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

Mechanisms of resistance

Mechanisms leading 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 has been established that the addition of the methoxyfloxacin methoxy group in the C8 position to the molecule structure 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 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., as well as 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 oral administration of moxifloxacin.

Decreased 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. Toxins Clostridium difficile not detected.

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), second-generation cephalosporins (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 (including methicillin-sensitive strains) *		Staphylococcus aureus (methicillin / ofloxacin 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 pneumophilia	Escherichia coli *
Acinetobacter baumanii	Klebsiella pneumoniae*
	Klebsiella oxytoca
	Citrobacter freundii *
	Enterobacter spp. (E. aerogenes, E. intermedins, 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 pneumoniae*
Chlamydia trachomatis *
Mycoplasma pneumoniae *
Mycoplasma hominis
Mycoplasma genitalium
Legionella pneumophila *
Coxiella burnetii

* Sensitivity to moxifloxacin is confirmed by clinical data.

⁺ The use of moxifloxacin 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" (AUС) / MIK₉₀, exceeds 125, and the maximum concentration in the blood plasma (C_max) / MIC₉₀is 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 (infusion for 1 h)
MIC₉₀ 0,125 mg / l	313	32,5
MIC₉₀ 0.25 mg / l	156	16.2
MIC₉₀ 0.5 mg / l	78	8,1

* AUIC - the area under the inhibitory curve (ratio AUC / MIC₉₀).

Pharmacokinetics:

Suction

After a single infusion of moxifloxacin at a dose of 400 mg for 1 hour C_mOh is achieved at the end of the infusion and is approximately 4.1 mg / L, which corresponds to its increase approximately 26% compared to the value of this indicator at admission moxifloxacin inside.

Exposure of moxifloxacin, determined by the indicator AUC, slightly higher than when taking moxifloxacin inside. Absolute bioavailability is approximately 91%. After multiple intravenous infusions of moxifloxacin in a dose of 400 mg for 1 hour 1 time per day Css^max and Css^min varies from 4.1 mg / L to 5.9 mg / L and from 0.43 mg / L to 0.84 mg / L, respectively. An average stable concentration of 4.4 mg / l is achieved at the end of the infusion.

Distribution

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

High concentrations moxifloxacin, exceeding those in the 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 the foci of inflammation (in the contents of blisters in the lesion of 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 moxifloxacin.

The balance for the initial compound and the metabolites of the 2nd phase is approximately 96-98%, which indicates the absence of oxidative metabolism. About 22% 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_mOh. Absorption of moxifloxacin did not depend on sex. Differences in indicators AUC and C_mOh were due to the difference in weight rather than sex and are not 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 the pharmacokinetics of 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

The concentration of moxifloxacin in patients with impaired liver function (class A and B according to the Child-Pugh classification) did not differ significantly from that in healthy volunteers or in patients with normal liver function (for use in patients with cirrhosis, see also "Special instructions ").

Indications:

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

- Community-acquired pneumonia, including community-acquired pneumonia, pathogens which are strains of microorganisms with multiple antibiotic resistance *;

- complicated skin and soft tissue infections (including an infected diabetic foot).

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

- Streptococcus pneumoniae with multiple antibiotic resistance include penicillin resistant strains 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;

- 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;

- use with other drugs that extend the interval QT (see the section "Interaction with other medicinal products");

- violations of liver function (class C according to the Child-Pugh classification) and an increase in the content of transaminases more than five times higher than the upper limit of the norm, due to the limited amount of clinical data.

Carefully:

- In diseases of the central nervous system (incl.suspicious of 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;

Patients with a genetic predisposition or an actual presence of a deficiency of glucose-6-phosphate dehydrogenase are prone to hemolytic reactions in the treatment with quinolones. As a result, in such patients moxifloxacin should be used with caution.

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:

Adults

The recommended dosage regimen for moxifloxacin is 400 mg (250 ml infusion solution) once a day for the infections mentioned above. Do not exceed the recommended dose.

Duration of treatment

The duration of treatment is determined by the localization and severity of the infection, as well as clinical effect. At the initial stages of treatment, Avelox®, a solution for infusions, can be used, and then, in the presence of indications, the drug can be prescribed for oral administration in the form of tablets coated with a film membrane.

- 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.

Do not exceed the recommended duration of treatment.

According to clinical studies, the duration of treatment with Avelox®, a solution for infusions, 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.

Violation of liver function (class A and B according to Child-Pugh classification)

Patients with hepatic dysfunction are not required to change the dosage regimen (for use in patients with cirrhosis see the 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, a change in the dosing regimen is not required.

Application the patients of typical ethnic groups

Dosage regimen changes are not required.

Mode of application

The drug is administered intravenously in the form of infusion lasting not less than 60 minutes both in undiluted form and in combination with the following compatible solutions (using a T-shaped adapter):

- water for injections;

- solution of sodium chloride 0.9%;

- solution of sodium chloride 1M;

- dextrose solution 5%;

- dextrose solution 10%;

- dextrose solution 40%;

- xylitol solution 20%;

- Ringer's solution;

- Ringer's lactate solution.

If the drug Avelox®, an infusion solution, is prescribed in conjunction with other drugs, then each drug should be administered separately.

A mixture of the drug Avelox®, infusion solution, with the above infusion solutions remains stable for 24 hours at room temperature.

At temperatures below +15 ° C, a precipitate may precipitate, which dissolves at room temperature (+15 ° C to +25 ° C). Do not store the drug in the refrigerator.

The preparation should be stored in a production package. Before use, visually check the solution for inclusions. Use only a clear, solution-free solution.

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 / 10,000 to <1/1000), very rarely ( <1/10000).

Systems bodies	Often	Infrequently	Rarely	Rarely
Infectious and parasitic diseases	Fungal superinfections
On the part of the hematopoiesis system		Anemia Leukopenia Neutropenia Thrombocytopenia Thrombocytosis Elongation prothrombin time / increase in international normalized ratio (MNO)	Change in concentration thromboplastin	Increase concentrationthe prothrombin / decrease in MNO
From the immune system		Allergic reactions Itching Rash Hives Eosinophilia	Anaphylactic / anaphylactoid reactions Angioedema, including laryngeal edema (potentiathreatening life)	Anaphylactic / anaphylactoid shock (including potentially life-threatening)
From the side of metabolism		Hyperlipidemia	Hyperglycaemia Hyperuricemia	Hypoglycaemia
Mental disorders		Anxiety psychomohypertension / agitation	Emotional lability Depression (at a very rare casesteens can behave with a tendency towardsdamage, 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)
From the nervous system	Head pain Dizziness	Paresthesia / Dysaesthesia Disturbance of taste sensitivity (including in very rare cases agevziyu) Confusion and disorientation Sleep Disorders Tremor Vertigo Drowsiness	Hypesesia Violations smell (including anosmia) Atypical dreaming Violation coordination (including gait disturbances due to dizziness or vertigo, in very rare cases leading to injury from falling, especially in elderly patients) Seizures with various clinical manifestations (including "grand mal" seizures) Violations attention Violations speech Amnesia Peripheral Neuropathy and polyneuropathy	Hyperesthesia
From the side of the 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 of hearing, including deafness (usually reversible)
From the cardiovascular system	Interval lengthening QT in patients with concomitant hypokalemia	Interval lengthening QT Heart palpitations 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 predisposing to arrhythmias states, such as clinically significant bradycardia, acute myocardial ischemia)
On the part of the respiratory system, the organon of the thorax and the mediastinum		Dyspnea (including asthmatic conditions)
From the gastrointestinal tract	Nausea Vomiting Stomach ache Diarrhea	Reduced appetite and reduced food intake Constipation Dyspepsia Flatulence Dastroenteritis (except erosive gastroenteritis) Выше Поamylase activity	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 function liver (including increased lactate dehydrogenase activity) Increased bilirubin concentration Increase in gamma activity-glutamyl transferase The increase in blood activity of alkaline phosphatase	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, Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening)
From the musculoskeletal and connective tissue		Arthralgia Myalgia	Tendonitis Increased muscle tonus and cramps Muscle weakness	Breaks tendons Arthritis Violations gait due to damage to the musculoskeletal system Increased Symptoms myasthenia gravis
From the side of 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 atcarry to damage to the kidneys, especially in elderly patients with pre-existing impaired renal function)
Are common frustratinglyand damage at the injection site	Local reactions at the site of administration	General malaise Pain for no apparent reason Sweating Phlebitis / thrombophlebitis at the site of administration	Edema

The frequency of these adverse events was higher in the group receiving treatment step (intravenous administration of the drug with its subsequent ingestion):

Often: increased activity of gamma-glutamyltransferase.

Infrequently: ventricular tachyarrhythmias, hypotension, 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, one should be guided by the clinical picture and carry out symptomatic maintenance therapy with ECG monitoring.

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)it takes.

Drugs that extend the interval QT

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 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).

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.

Despite the fact that there is no interaction between moxifloxacin and warfarin, in patients receiving concomitant treatment with these drugs, it is necessary to monitor the INR and, if necessary, adjust the dose of indirect anticoagulantsnts.

Digoxin

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

Activated carbon

With intravenous administration of moxifloxacin with simultaneous oral administration of activated charcoal, the systemic bioavailability of the drug is slightly reduced (by approximately 20%) due to adsorption of moxifloxacin in the lumen of the gastrointestinal tract during enterohepatic recirculation.

Incompatibility

It is impossible to produce an infusion solution of moxifloxacin simultaneously with other solutions incompatible with it, which include:

- A solution of sodium chloride 10%;

- A solution of sodium chloride 20%:

- A solution of sodium bicarbonate 4.2%;

- A solution of sodium hydrogen carbonate 8.4%.

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. 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 increasing drug concentration, therefore, do not exceed the recommended dose and infusion rate (400 mg for 60 min). 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 Avelox® received cardiovascular complications and lethal cases associated with the prolongation of the QT interval. When using Avelox®, the risk of developing ventricular arrhythmias in patients with predisposing arrhythmias may increase.

In this regard, the drug 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 disturbances, especially notcorrected hypokalemia; clinically significant bradycardia; clinically significant heart failure with a reduced fraction of the left ventricular ejection; in the presence of a history of rhythm disturbances, accompanied by a clinical symptomtomatics;

- use 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 using Avelox®, cases of fulminant hepatitis, potentially leading to liver failure (including fatal cases), have been reported (see "Side effect" section). The patient should be informed that if symptoms of hepatic insufficiency occur, the doctor should be consulted before continuing treatment with Avelox®

When using the drug Avelox®, cases of developing bullous skin lesions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported. 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 that predispose to seizures or reduce the threshold of seizure activity.

The use of broad-spectrum antibacterial drugs, including Avelox®, 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 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, the drug should be stopped and unloaded.

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

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 moxifloxacin 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 undergoing treatment with quinolones, including Avelox®, described cases of sensory or sensorimotor polyneuropathy leading to paresthesia, kinesthesias, dysesthesias, or weakness. Patients undergoing treatment with Avelox^®, should be warned about the need to immediately seek medical attention 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 "Side effect" section).If patients develop such reactions, Avelox® should be discontinued and appropriate measures taken. Caution should be exercised when using Avelox® in patients with psychosis and / or psychiatric illnesses in the anamnesis.

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. Against the background of therapy with Avelox^® dysglycemia 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, careful monitoring of the concentration of glucose in the blood is recommended (see section "Side effect").

Patients who follow a diet with a low salt content (with heart failure, kidney failure, with nephrotic syndrome) should take into account that the infusion solution contains sodium chloride.

The daily dose of sodium in the preparation is 34 mmol.

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:Solution for infusion, 1.6 mg / ml.

Packaging:

Bottles: 250 ml in a bottle of colorless glass, with a capacity of 300 ml, sealed with a stopper of chlorobutyl or bromobutyl gray, an aluminum crimping ring and a plastic cap. 1 bottle with instructions for use in a cardboard pack.

Containers made of polyolefin: 250 ml per container polyolefin for single-use infusion solutions with one port. Each container is sealed in a polyolefin / polyester / aluminum / polypropylene protective bag.

4 or 12 polyolefin containers together with an appropriate number of instructions for use in a cardboard box.

Storage conditions:

Store at temperatures between 15 and 30 ° C.

Keep out of the reach of children.

Shelf life:

Bottles: 5 years.

Containers made of polyolefin: 3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N012034 / 02

Date of registration:06.05.2010 / 09.02.2015

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®)